Skip to content
2000
image of A Comprehensive Analysis of the ITIH Family Across Multiple Cancer Types and an Initial Investigation of ITIH1 in Gastric Cancer

Abstract

Introduction

The ITIH family, crucial for extracellular matrix stability and cancer progression, is underexplored in multi-omic profiles and immune microenvironments; this study analyzes their roles across cancers and ITIH1’s function in gastric cancer to reveal diagnostic, prognostic, and therapeutic potential.

Methods

We analyzed RNA-seq, protein expr ession, and clinical data from 33 cancer types and 24 non-cancerous conditions using TCGA, GTEx, GEO, CPTAC, and IMvigor210 datasets. Methods included differential expression analysis, ROC curve assessment for diagnostic potential, Cox regression and Kaplan-Meier survival analyses for prognostic value, GSEA for pathway enrichment, and molecular docking for ITIH1-targeted small molecule screening. Immune microenvironment interactions, tumor mutational burden (TMB), microsatellite instability (MSI), and immunotherapy response were evaluated. experiments validated ITIH1’s role in gastric cancer using qRT-PCR, Western blotting, siRNA knockdown, and functional assays.

Results

ITIH family genes exhibited differential expression across cancers and non-cancerous conditions, with ITIH1, ITIH4, and ITIH5 showing high diagnostic potential (AUC > 0.90 in multiple cancers). ITIH1 was a risk factor for poor survival in gastric cancer ( < 0.05). Lower ITIH scores correlated with improved survival in patients receiving immune checkpoint inhibitors ( < 0.05). ITIH genes showed strong correlations with immune checkpoints (PD-1, CTLA-4), TMB, and MSI. Molecular docking identified six small molecules, including Entinostat, with high binding affinity for ITIH1 (-8.4 kcal/mol). ITIH1 knockdown in gastric cancer cell lines (HGC-27, AGS) significantly reduced proliferation, migration, and invasion ( < 0.01).

Discussion

This study underscores the ITIH family's critical role as diagnostic and prognostic biomarkers across various cancers and non-cancerous conditions, with ITIH1's therapeutic potential in gastric cancer highlighted through its impact on tumor progression, though limitations include discrepancies in some ITIH gene expressions between and settings, necessitating further validation.

Conclusion

Our findings highlight the ITIH family's potential as diagnostic biomarkers, prognostic indicators, and therapeutic targets, particularly in gastric cancer. The identification of ITIH1 inhibitors and their association with immune checkpoints, TMB, and MSI paves the way for improved diagnostics, targeted therapies, and immunotherapy predictions, enhancing patient outcomes across diseases.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673375809250730142009
2025-08-12
2025-11-06

  • From This Site

    /content/journals/cmc/10.2174/0109298673375809250730142009
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  2. Hegde P.S. Chen D.S. Top 10 challenges in cancer immunotherapy. Immunity 2020 52 1 17 35 10.1016/j.immuni.2019.12.011 31940268
    [Google Scholar]
  3. Zhuo L. Hascall V.C. Kimata K. Inter-α-trypsin inhibitor, a covalent protein-glycosaminoglycan-protein complex. J. Biol. Chem. 2004 279 37 38079 38082 10.1074/jbc.R300039200 15151994
    [Google Scholar]
  4. Zhuo L. Kimata K. Structure and function of inter-α-trypsin inhibitor heavy chains. Connect. Tissue Res. 2008 49 5 311 320 10.1080/03008200802325458 18991084
    [Google Scholar]
  5. Hutadilok N. Ghosh P. Brooks P.M. Binding of haptoglobin, inter-alpha-trypsin inhibitor, and alpha 1 proteinase inhibitor to synovial fluid hyaluronate and the influence of these proteins on its degradation by oxygen derived free radicals. Ann. Rheum. Dis. 1988 47 5 377 385 10.1136/ard.47.5.377 2455485
    [Google Scholar]
  6. He H. Li W. Tseng D.Y. Zhang S. Chen S.Y. Day A.J. Tseng S.C.G. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-α-inhibitor (HC*HA) purified from extracts of human amniotic membrane. J. Biol. Chem. 2009 284 30 20136 20146 10.1074/jbc.M109.021881 19491101
    [Google Scholar]
  7. Bost F. Diarra-Mehrpour M. Martin J.P. Inter-α-trypsin inhibitor proteoglycan family. Eur. J. Biochem. 1998 252 3 339 346 10.1046/j.1432‑1327.1998.2520339.x 9546647
    [Google Scholar]
  8. Himmelfarb M. Klopocki E. Grube S. Staub E. Klaman I. Hinzmann B. Kristiansen G. Rosenthal A. Dürst M. Dahl E. ITIH5, a novel member of the inter-α-trypsin inhibitor heavy chain family is downregulated in breast cancer. Cancer Lett. 2004 204 1 69 77 10.1016/j.canlet.2003.09.011 14744536
    [Google Scholar]
  9. Chen L. Mao S.J. McLean L.R. Powers R.W. Larsen W.J. Proteins of the inter-alpha-trypsin inhibitor family stabilize the cumulus extracellular matrix through their direct binding with hyaluronic acid. J. Biol. Chem. 1994 269 45 28282 28287 10.1016/S0021‑9258(18)46925‑6 7525572
    [Google Scholar]
  10. Paris S. Sesboüé R. Delpech B. Chauzy C. Thiberville L. Martin J.P. Frébourg T. Diarra-Mehrpour M. Inhibition of tumor growth and metastatic spreading by overexpression of inter-alpha-trypsin inhibitor family chains. Int. J. Cancer 2002 97 5 615 620 10.1002/ijc.10120 11807786
    [Google Scholar]
  11. Hamm A. Veeck J. Bektas N. Wild P.J. Hartmann A. Heindrichs U. Kristiansen G. Werbowetski-Ogilvie T. Del Maestro R. Knuechel R. Dahl E. Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis. BMC Cancer 2008 8 1 25 10.1186/1471‑2407‑8‑25 18226209
    [Google Scholar]
  12. Chen M. Ma J. Xie X. Su M. Zhao D. Serum ITIH5 as a novel diagnostic biomarker in cholangiocarcinoma. Cancer Sci. 2024 115 5 1665 1679 10.1111/cas.16143 38475675
    [Google Scholar]
  13. Li X Li B Li B Guo T Sun Z Li X Chen L Chen W Chen P Mao Y Zeng Y. ITIH4: Effective serum marker, early warning and diagnosis, hepatocellular carcinoma. Pathol Oncol Res 2017 24 3 663 10.1007/s12253‑017‑0285‑4
    [Google Scholar]
  14. He K. He S. Su M. Inter-alpha-trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk, activity, and treatment outcomes of rheumatoid arthritis. J. Clin. Lab. Anal. 2022 36 3 e24231 10.1002/jcla.24231 35064701
    [Google Scholar]
  15. Jiao Y. Yang M. Fang L. Yan Y. Fu Z. Li M. Li L. Liu Z. Hu X. Wu B. Shi Y. Kang C. Shen Z. Peng G. Serum proteomic analysis identified ITIH4 as a potential novel biomarker for feline infectious peritonitis. J. Proteomics 2025 310 105338 8 10.1016/j.jprot.2024.105338 39454824
    [Google Scholar]
  16. Weinstein J.N. Collisson E.A. Mills G.B. Shaw K.R.M. Ozenberger B.A. Ellrott K. Shmulevich I. Sander C. Stuart J.M. Cancer Genome Atlas Research Network The cancer genome atlas pan-cancer analysis project. Nat. Genet. 2013 45 10 1113 1120 10.1038/ng.2764 24071849
    [Google Scholar]
  17. Hoadley K.A. Yau C. Hinoue T. Wolf D.M. Lazar A.J. Drill E. Shen R. Taylor A.M. Cherniack A.D. Thorsson V. Akbani R. Bowlby R. Wong C.K. Wiznerowicz M. Sanchez-Vega F. Robertson A.G. Schneider B.G. Lawrence M.S. Noushmehr H. Malta T.M. Caesar-Johnson S.J. Demchok J.A. Felau I. Kasapi M. Ferguson M.L. Hutter C.M. Sofia H.J. Tarnuzzer R. Wang Z. Yang L. Zenklusen J.C. Zhang J.J. Chudamani S. Liu J. Lolla L. Naresh R. Pihl T. Sun Q. Wan Y. Wu Y. Cho J. DeFreitas T. Frazer S. Gehlenborg N. Getz G. Heiman D.I. Kim J. Lawrence M.S. Lin P. Meier S. Noble M.S. Saksena G. Voet D. Zhang H. Bernard B. Chambwe N. Dhankani V. Knijnenburg T. Kramer R. Leinonen K. Liu Y. Miller M. Reynolds S. Shmulevich I. Thorsson V. Zhang W. Akbani R. Broom B.M. Hegde A.M. Ju Z. Kanchi R.S. Korkut A. Li J. Liang H. Ling S. Liu W. Lu Y. Mills G.B. Ng K-S. Rao A. Ryan M. Wang J. Weinstein J.N. Zhang J. Abeshouse A. Armenia J. Chakravarty D. Chatila W.K. de Bruijn I. Gao J. Gross B.E. Heins Z.J. Kundra R. La K. Ladanyi M. Luna A. Nissan M.G. Ochoa A. Phillips S.M. Reznik E. Sanchez-Vega F. Sander C. Schultz N. Sheridan R. Sumer S.O. Sun Y. Taylor B.S. Wang J. Zhang H. Anur P. Peto M. Spellman P. Benz C. Stuart J.M. Wong C.K. Yau C. Hayes D.N. Parker J.S. Wilkerson M.D. Ally A. Balasundaram M. Bowlby R. Brooks D. Carlsen R. Chuah E. Dhalla N. Holt R. Jones S.J.M. Kasaian K. Lee D. Ma Y. Marra M.A. Mayo M. Moore R.A. Mungall A.J. Mungall K. Robertson A.G. Sadeghi S. Schein J.E. Sipahimalani P. Tam A. Thiessen N. Tse K. Wong T. Berger A.C. Beroukhim R. Cherniack A.D. Cibulskis C. Gabriel S.B. Gao G.F. Ha G. Meyerson M. Schumacher S.E. Shih J. Kucherlapati M.H. Kucherlapati R.S. Baylin S. Cope L. Danilova L. Bootwalla M.S. Lai P.H. Maglinte D.T. Van Den Berg D.J. Weisenberger D.J. Auman J.T. Balu S. Bodenheimer T. Fan C. Hoadley K.A. Hoyle A.P. Jefferys S.R. Jones C.D. Meng S. Mieczkowski P.A. Mose L.E. Perou A.H. Perou C.M. Roach J. Shi Y. Simons J.V. Skelly T. Soloway M.G. Tan D. Veluvolu U. Fan H. Hinoue T. Laird P.W. Shen H. Zhou W. Bellair M. Chang K. Covington K. Creighton C.J. Dinh H. Doddapaneni H.V. Donehower L.A. Drummond J. Gibbs R.A. Glenn R. Hale W. Han Y. Hu J. Korchina V. Lee S. Lewis L. Li W. Liu X. Morgan M. Morton D. Muzny D. Santibanez J. Sheth M. Shinbrot E. Wang L. Wang M. Wheeler D.A. Xi L. Zhao F. Hess J. Appelbaum E.L. Bailey M. Cordes M.G. Ding L. Fronick C.C. Fulton L.A. Fulton R.S. Kandoth C. Mardis E.R. McLellan M.D. Miller C.A. Schmidt H.K. Wilson R.K. Crain D. Curley E. Gardner J. Lau K. Mallery D. Morris S. Paulauskis J. Penny R. Shelton C. Shelton T. Sherman M. Thompson E. Yena P. Bowen J. Gastier-Foster J.M. Gerken M. Leraas K.M. Lichtenberg T.M. Ramirez N.C. Wise L. Zmuda E. Corcoran N. Costello T. Hovens C. Carvalho A.L. de Carvalho A.C. Fregnani J.H. Longatto-Filho A. Reis R.M. Scapulatempo-Neto C. Silveira H.C.S. Vidal D.O. Burnette A. Eschbacher J. Hermes B. Noss A. Singh R. Anderson M.L. Castro P.D. Ittmann M. Huntsman D. Kohl B. Le X. Thorp R. Andry C. Duffy E.R. Lyadov V. Paklina O. Setdikova G. Shabunin A. Tavobilov M. McPherson C. Warnick R. Berkowitz R. Cramer D. Feltmate C. Horowitz N. Kibel A. Muto M. Raut C.P. Malykh A. Barnholtz-Sloan J.S. Barrett W. Devine K. Fulop J. Ostrom Q.T. Shimmel K. Wolinsky Y. Sloan A.E. De Rose A. Giuliante F. Goodman M. Karlan B.Y. Hagedorn C.H. Eckman J. Harr J. Myers J. Tucker K. Zach L.A. Deyarmin B. Hu H. Kvecher L. Larson C. Mural R.J. Somiari S. Vicha A. Zelinka T. Bennett J. Iacocca M. Rabeno B. Swanson P. Latour M. Lacombe L. Têtu B. Bergeron A. McGraw M. Staugaitis S.M. Chabot J. Hibshoosh H. Sepulveda A. Su T. Wang T. Potapova O. Voronina O. Desjardins L. Mariani O. Roman-Roman S. Sastre X. Stern M-H. Cheng F. Signoretti S. Berchuck A. Bigner D. Lipp E. Marks J. McCall S. McLendon R. Secord A. Sharp A. Behera M. Brat D.J. Chen A. Delman K. Force S. Khuri F. Magliocca K. Maithel S. Olson J.J. Owonikoko T. Pickens A. Ramalingam S. Shin D.M. Sica G. Van Meir E.G. Zhang H. Eijckenboom W. Gillis A. Korpershoek E. Looijenga L. Oosterhuis W. Stoop H. van Kessel K.E. Zwarthoff E.C. Calatozzolo C. Cuppini L. Cuzzubbo S. DiMeco F. Finocchiaro G. Mattei L. Perin A. Pollo B. Chen C. Houck J. Lohavanichbutr P. Hartmann A. Stoehr C. Stoehr R. Taubert H. Wach S. Wullich B. Kycler W. Murawa D. Wiznerowicz M. Chung K. Edenfield W.J. Martin J. Baudin E. Bubley G. Bueno R. De Rienzo A. Richards W.G. Kalkanis S. Mikkelsen T. Noushmehr H. Scarpace L. Girard N. Aymerich M. Campo E. Giné E. Guillermo A.L. Van Bang N. Hanh P.T. Phu B.D. Tang Y. Colman H. Evason K. Dottino P.R. Martignetti J.A. Gabra H. Juhl H. Akeredolu T. Stepa S. Hoon D. Ahn K. Kang K.J. Beuschlein F. Breggia A. Birrer M. Bell D. Borad M. Bryce A.H. Castle E. Chandan V. Cheville J. Copland J.A. Farnell M. Flotte T. Giama N. Ho T. Kendrick M. Kocher J-P. Kopp K. Moser C. Nagorney D. O’Brien D. O’Neill B.P. Patel T. Petersen G. Que F. Rivera M. Roberts L. Smallridge R. Smyrk T. Stanton M. Thompson R.H. Torbenson M. Yang J.D. Zhang L. Brimo F. Ajani J.A. Gonzalez A.M.A. Behrens C. Bondaruk Broaddus R. Czerniak B. Esmaeli B. Fujimoto J. Gershenwald J. Guo C. Lazar A.J. Logothetis C. Meric-Bernstam F. Moran C. Ramondetta L. Rice D. Sood A. Tamboli P. Thompson T. Troncoso P. Tsao A. Wistuba I. Carter C. Haydu L. Hersey P. Jakrot V. Kakavand H. Kefford R. Lee K. Long G. Mann G. Quinn M. Saw R. Scolyer R. Shannon K. Spillane A. Stretch J. Synott M. Thompson J. Wilmott J. Al-Ahmadie H. Chan T.A. Ghossein R. Gopalan A. Levine D.A. Reuter V. Singer S. Singh B. Tien N.V. Broudy T. Mirsaidi C. Nair P. Drwiega P. Miller J. Smith J. Zaren H. Park J-W. Hung N.P. Kebebew E. Linehan W.M. Metwalli A.R. Pacak K. Pinto P.A. Schiffman M. Schmidt L.S. Vocke C.D. Wentzensen N. Worrell R. Yang H. Moncrieff M. Goparaju C. Melamed J. Pass H. Botnariuc N. Caraman I. Cernat M. Chemencedji I. Clipca A. Doruc S. Gorincioi G. Mura S. Pirtac M. Stancul I. Tcaciuc D. Albert M. Alexopoulou I. Arnaout A. Bartlett J. Engel J. Gilbert S. Parfitt J. Sekhon H. Thomas G. Rassl D.M. Rintoul R.C. Bifulco C. Tamakawa R. Urba W. Hayward N. Timmers H. Antenucci A. Facciolo F. Grazi G. Marino M. Merola R. de Krijger R. Gimenez-Roqueplo A-P. Piché A. Chevalier S. McKercher G. Birsoy K. Barnett G. Brewer C. Farver C. Naska T. Pennell N.A. Raymond D. Schilero C. Smolenski K. Williams F. Morrison C. Borgia J.A. Liptay M.J. Pool M. Seder C.W. Junker K. Omberg L. Dinkin M. Manikhas G. Alvaro D. Bragazzi M.C. Cardinale V. Carpino G. Gaudio E. Chesla D. Cottingham S. Dubina M. Moiseenko F. Dhanasekaran R. Becker K-F. Janssen K-P. Slotta-Huspenina J. Abdel-Rahman M.H. Aziz D. Bell S. Cebulla C.M. Davis A. Duell R. Elder J.B. Hilty J. Kumar B. Lang J. Lehman N.L. Mandt R. Nguyen P. Pilarski R. Rai K. Schoenfield L. Senecal K. Wakely P. Hansen P. Lechan R. Powers J. Tischler A. Grizzle W.E. Sexton K.C. Kastl A. Henderson J. Porten S. Waldmann J. Fassnacht M. Asa S.L. Schadendorf D. Couce M. Graefen M. Huland H. Sauter G. Schlomm T. Simon R. Tennstedt P. Olabode O. Nelson M. Bathe O. Carroll P.R. Chan J.M. Disaia P. Glenn P. Kelley R.K. Landen C.N. Phillips J. Prados M. Simko J. Smith-McCune K. VandenBerg S. Roggin K. Fehrenbach A. Kendler A. Sifri S. Steele R. Jimeno A. Carey F. Forgie I. Mannelli M. Carney M. Hernandez B. Campos B. Herold-Mende C. Jungk C. Unterberg A. von Deimling A. Bossler A. Galbraith J. Jacobus L. Knudson M. Knutson T. Ma D. Milhem M. Sigmund R. Godwin A.K. Madan R. Rosenthal H.G. Adebamowo C. Adebamowo S.N. Boussioutas A. Beer D. Giordano T. Mes-Masson A-M. Saad F. Bocklage T. Landrum L. Mannel R. Moore K. Moxley K. Postier R. Walker J. Zuna R. Feldman M. Valdivieso F. Dhir R. Luketich J. Pinero E.M.M. Quintero-Aguilo M. Carlotti C.G. Jr Dos Santos J.S. Kemp R. Sankarankuty A. Tirapelli D. Catto J. Agnew K. Swisher E. Creaney J. Robinson B. Shelley C.S. Godwin E.M. Kendall S. Shipman C. Bradford C. Carey T. Haddad A. Moyer J. Peterson L. Prince M. Rozek L. Wolf G. Bowman R. Fong K.M. Yang I. Korst R. Rathmell W.K. Fantacone-Campbell J.L. Hooke J.A. Kovatich A.J. Shriver C.D. DiPersio J. Drake B. Govindan R. Heath S. Ley T. Van Tine B. Westervelt P. Rubin M.A. Lee J.I. Aredes N.D. Mariamidze A. Stuart J.M. Benz C.C. Laird P.W. Cancer Genome Atlas Network Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell 2018 173 2 291 304.e6 10.1016/j.cell.2018.03.022 29625048
    [Google Scholar]
  18. Aguet F. Anand S. Ardlie K.G. Gabriel S. Getz G.A. Graubert A. Hadley K. Handsaker R.E. Huang K.H. Kashin S. Li X. MacArthur D.G. Meier S.R. Nedzel J.L. Nguyen D.T. Segrè A.V. Todres E. Balliu B. Barbeira A.N. Battle A. Bonazzola R. Brown A. Brown C.D. Castel S.E. Conrad D.F. Cotter D.J. Cox N. Das S. de Goede O.M. Dermitzakis E.T. Einson J. Engelhardt B.E. Eskin E. Eulalio T.Y. Ferraro N.M. Flynn E.D. Fresard L. Gamazon E.R. Garrido-Martín D. Gay N.R. Gloudemans M.J. Guigó R. Hame A.R. He Y. Hoffman P.J. Hormozdiari F. Hou L. Im H.K. Jo B. Kasela S. Kellis M. Kim-Hellmuth S. Kwong A. Lappalainen T. Li X. Liang Y. Mangul S. Mohammadi P. Montgomery S.B. Muñoz-Aguirre M. Nachun D.C. Nobel A.B. Oliva M. Park Y.S. Park Y. Parsana P. Rao A.S. Reverter F. Rouhana J.M. Sabatti C. Saha A. Stephens M. Stranger B.E. Strober B.J. Teran N.A. Viñuela A. Wang G. Wen X. Wright F. Wucher V. Zou Y. Ferreira P.G. Li G. Melé M. Yeger-Lotem E. Barcus M.E. Bradbury D. Krubit T. McLean J.A. Qi L. Robinson K. Roche N.V. Smith A.M. Sobin L. Tabor D.E. Undale A. Bridge J. Brigham L.E. Foster B.A. Gillard B.M. Hasz R. Hunter M. Johns C. Johnson M. Karasik E. Kopen G. Leinweber W.F. McDonald A. Moser M.T. Myer K. Ramsey K.D. Roe B. Shad S. Thomas J.A. Walters G. Washington M. Wheeler J. Jewell S.D. Rohrer D.C. Valley D.R. Davis D.A. Mash D.C. Branton P.A. Barker L.K. Gardiner H.M. Mosavel M. Siminoff L.A. Flicek P. Haeussler M. Juettemann T. Kent W.J. Lee C.M. Powell C.C. Rosenbloom K.R. Ruffier M. Sheppard D. Taylor K. Trevanion S.J. Zerbino D.R. Abell N.S. Akey J. Chen L. Demanelis K. Doherty J.A. Feinberg A.P. Hansen K.D. Hickey P.F. Jasmine F. Jiang L. Kaul R. Kibriya M.G. Li J.B. Li Q. Lin S. Linder S.E. Pierce B.L. Rizzardi L.F. Skol A.D. Smith K.S. Snyder M. Stamatoyannopoulos J. Tang H. Wang M. Carithers L.J. Guan P. Koester S.E. Little A.R. Moore H.M. Nierras C.R. Rao A.K. Vaught J.B. Volpi S. GTEx Consortium The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 2020 369 6509 1318 1330 10.1126/science.aaz1776 32913098
    [Google Scholar]
  19. Carithers L.J. Moore H.M. The Genotype-Tissue Expression (GTEx) project. Biopreserv. Biobank. 2015 13 5 307 308 10.1089/bio.2015.29031.hmm 26484569
    [Google Scholar]
  20. Barrett T. Wilhite S.E. Ledoux P. Evangelista C. Kim I.F. Tomashevsky M. Marshall K.A. Phillippy K.H. Sherman P.M. Holko M. Yefanov A. Lee H. Zhang N. Robertson C.L. Serova N. Davis S. Soboleva A. NCBI GEO: Archive for functional genomics data sets—update. Nucleic Acids Res. 2012 41 D1 D991 D995 10.1093/nar/gks1193 23193258
    [Google Scholar]
  21. Clough E. Barrett T. The gene expression omnibus database. Methods Mol. Biol. 2016 1418 93 110 10.1007/978‑1‑4939‑3578‑9_5 27008011
    [Google Scholar]
  22. Mariathasan S. Turley S.J. Nickles D. Castiglioni A. Yuen K. Wang Y. Kadel E.E. III Koeppen H. Astarita J.L. Cubas R. Jhunjhunwala S. Banchereau R. Yang Y. Guan Y. Chalouni C. Ziai J. Şenbabaoğlu Y. Santoro S. Sheinson D. Hung J. Giltnane J.M. Pierce A.A. Mesh K. Lianoglou S. Riegler J. Carano R.A.D. Eriksson P. Höglund M. Somarriba L. Halligan D.L. van der Heijden M.S. Loriot Y. Rosenberg J.E. Fong L. Mellman I. Chen D.S. Green M. Derleth C. Fine G.D. Hegde P.S. Bourgon R. Powles T. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 2018 554 7693 544 548 10.1038/nature25501 29443960
    [Google Scholar]
  23. Braun D.A. Hou Y. Bakouny Z. Ficial M. Sant’ Angelo M. Forman J. Ross-Macdonald P. Berger A.C. Jegede O.A. Elagina L. Steinharter J. Sun M. Wind-Rotolo M. Pignon J.C. Cherniack A.D. Lichtenstein L. Neuberg D. Catalano P. Freeman G.J. Sharpe A.H. McDermott D.F. Van Allen E.M. Signoretti S. Wu C.J. Shukla S.A. Choueiri T.K. Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nat. Med. 2020 26 6 909 918 10.1038/s41591‑020‑0839‑y 32472114
    [Google Scholar]
  24. Zhang H. Liu T. Zhang Z. Payne S.H. Zhang B. McDermott J.E. Zhou J.Y. Petyuk V.A. Chen L. Ray D. Sun S. Yang F. Chen L. Wang J. Shah P. Cha S.W. Aiyetan P. Woo S. Tian Y. Gritsenko M.A. Clauss T.R. Choi C. Monroe M.E. Thomas S. Nie S. Wu C. Moore R.J. Yu K.H. Tabb D.L. Fenyö D. Bafna V. Wang Y. Rodriguez H. Boja E.S. Hiltke T. Rivers R.C. Sokoll L. Zhu H. Shih I.M. Cope L. Pandey A. Zhang B. Snyder M.P. Levine D.A. Smith R.D. Chan D.W. Rodland K.D. CPTAC Investigators. Integrated proteogenomic characterization of human high- grade serous ovarian. Cancer Cell 2016 166 3 755 765 10.1016/j.cell.2016.05.069 27372738
    [Google Scholar]
  25. Clark D.J. Dhanasekaran S.M. Petralia F. Pan J. Song X. Hu Y. da Veiga Leprevost F. Reva B. Lih T.S.M. Chang H.Y. Ma W. Huang C. Ricketts C.J. Chen L. Krek A. Li Y. Rykunov D. Li Q.K. Chen L.S. Ozbek U. Vasaikar S. Wu Y. Yoo S. Chowdhury S. Wyczalkowski M.A. Ji J. Schnaubelt M. Kong A. Sethuraman S. Avtonomov D.M. Ao M. Colaprico A. Cao S. Cho K.C. Kalayci S. Ma S. Liu W. Ruggles K. Calinawan A. Gümüş Z.H. Geiszler D. Kawaler E. Teo G.C. Wen B. Zhang Y. Keegan S. Li K. Chen F. Edwards N. Pierorazio P.M. Chen X.S. Pavlovich C.P. Hakimi A.A. Brominski G. Hsieh J.J. Antczak A. Omelchenko T. Lubinski J. Wiznerowicz M. Linehan W.M. Kinsinger C.R. Thiagarajan M. Boja E.S. Mesri M. Hiltke T. Robles A.I. Rodriguez H. Qian J. Fenyö D. Zhang B. Ding L. Schadt E. Chinnaiyan A.M. Zhang Z. Omenn G.S. Cieslik M. Chan D.W. Nesvizhskii A.I. Wang P. Zhang H. Hashimi A.S. Pico A.R. Karpova A. Charamut A. Paulovich A.G. Perou A.M. Malovannaya A. Marrero-Oliveras A. Agarwal A. Hindenach B. Pruetz B. Kim B-J. Druker B.J. Newton C.J. Birger C. Jones C.D. Tognon C. Mani D.R. Valley D.R. Rohrer D.C. Zhou D.C. Tansil D. Chesla D. Heiman D. Wheeler D. Tan D. Chan D. Demir E. Malc E. Modugno F. Getz G. Hostetter G. Wilson G.D. Hart G.W. Zhu H. Liu H. Culpepper H. Sun H. Zhou H. Day J. Suh J. Huang J. McDermott J. Whiteaker J.R. Tyner J.W. Eschbacher J. Chen J. McGee J. Zhu J. Ketchum K.A. Rodland K.D. Clauser K. Robinson K. Krug K. Hoadley K.A. Um K.S. Elburn K. Holloway K. Wang L-B. Blumenberg L. Hannick L. Qi L. Sokoll L.J. Cornwell M.I. Loriaux M. Domagalski M.J. Gritsenko M.A. Anderson M. Monroe M.E. Ellis M.J. Dyer M. Anurag M. Burke M.C. Borucki M. Gillette M.A. Birrer M.J. Lewis M. Ittmann M.M. Smith M. Vernon M. Chaikin M. Chheda M.G. Khan M. Roche N. Edwards N.J. Vatanian N. Tignor N. Beckmann N. Grady P. Castro P. Piehowski P. McGarvey P.B. Mieczkowski P. Hariharan P. Gao Q. Dhir R. Kothadia R.B. Thangudu R.R. Montgomery R. Jayasinghe R.G. Smith R.D. Edwards R. Zelt R. Bremner R. Liu R. Hong R. Mareedu S. Payne S.H. Cottingham S. Markey S.P. Jewell S.D. Patel S. Satpathy S. Richey S. Davies S.R. Cai S. Boca S.M. Patil S. Sengupta S. Carter S. Gabriel S. Thomas S.N. De Young S. Stein S.E. Carr S.A. Foltz S.M. Hilsenbeck S. Krubit T. Liu T. Skelly T. Westbrook T. Borate U. Velvulou U. Petyuk V.A. Bocik W.E. Chen X. Shi Y. Geffen Y. Lu Y. Wang Y. Maruvka Y. Li Z. Shi Z. Tu Z. Clinical Proteomic Tumor Analysis Consortium Integrated proteogenomic characterization of clear cell renal cell carcinoma. Cell 2019 179 4 964 983.e31 10.1016/j.cell.2019.10.007 31675502
    [Google Scholar]
  26. Uhlén M. Fagerberg L. Hallström B.M. Lindskog C. Oksvold P. Mardinoglu A. Sivertsson Å. Kampf C. Sjöstedt E. Asplund A. Olsson I. Edlund K. Lundberg E. Navani S. Szigyarto C.A.K. Odeberg J. Djureinovic D. Takanen J.O. Hober S. Alm T. Edqvist P.H. Berling H. Tegel H. Mulder J. Rockberg J. Nilsson P. Schwenk J.M. Hamsten M. von Feilitzen K. Forsberg M. Persson L. Johansson F. Zwahlen M. von Heijne G. Nielsen J. Pontén F. Tissue-based map of the human proteome. Science 2015 347 6220 1260419 10.1126/science.1260419 25613900
    [Google Scholar]
  27. Thul P.J. Åkesson L. Wiking M. Mahdessian D. Geladaki A. Ait Blal H. Alm T. Asplund A. Björk L. Breckels L.M. Bäckström A. Danielsson F. Fagerberg L. Fall J. Gatto L. Gnann C. Hober S. Hjelmare M. Johansson F. Lee S. Lindskog C. Mulder J. Mulvey C.M. Nilsson P. Oksvold P. Rockberg J. Schutten R. Schwenk J.M. Sivertsson Å. Sjöstedt E. Skogs M. Stadler C. Sullivan D.P. Tegel H. Winsnes C. Zhang C. Zwahlen M. Mardinoglu A. Pontén F. von Feilitzen K. Lilley K.S. Uhlén M. Lundberg E. A subcellular map of the human proteome. Science 2017 356 6340 eaal3321 10.1126/science.aal3321 28495876
    [Google Scholar]
  28. Tomczak K. Czerwińska P. Wiznerowicz M. Review The Cancer Genome Atlas (TCGA): An immeasurable source of knowledge. Contemp. Oncol. (Pozn.) 2015 1A 1A 68 77 10.5114/wo.2014.47136 25691825
    [Google Scholar]
  29. Robin X. Turck N. Hainard A. Tiberti N. Lisacek F. Sanchez J.C. Müller M. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 2011 12 1 77 10.1186/1471‑2105‑12‑77 21414208
    [Google Scholar]
  30. Stel V.S. Dekker F.W. Tripepi G. Zoccali C. Jager K.J. Survival analysis II: Cox regression. Nephron Clin. Pract. 2011 119 3 c255 c260 10.1159/000328916 21921637
    [Google Scholar]
  31. Kishore J. Goel M.K. Khanna P. Understanding survival analysis: Kaplan-Meier estimate. Int. J. Ayurveda Res. 2010 1 4 274 278 10.4103/0974‑7788.76794 21455458
    [Google Scholar]
  32. Liberzon A. Birger C. Thorvaldsdóttir H. Ghandi M. Mesirov J.P. Tamayo P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 2015 1 6 417 425 10.1016/j.cels.2015.12.004 26771021
    [Google Scholar]
  33. Reimand J. Isserlin R. Voisin V. Kucera M. Tannus-Lopes C. Rostamianfar A. Wadi L. Meyer M. Wong J. Xu C. Merico D. Bader G.D. Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap. Nat. Protoc. 2019 14 2 482 517 10.1038/s41596‑018‑0103‑9 30664679
    [Google Scholar]
  34. Yu G. Wang L.G. Han Y. He Q.Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012 16 5 284 287 10.1089/omi.2011.0118 22455463
    [Google Scholar]
  35. Kanehisa M. Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000 28 1 27 30 10.1093/nar/28.1.27 10592173
    [Google Scholar]
  36. Ru B. Wong C.N. Tong Y. Zhong J.Y. Zhong S.S.W. Wu W.C. Chu K.C. Wong C.Y. Lau C.Y. Chen I. Chan N.W. Zhang J. TISIDB: An integrated repository portal for tumor–immune system interactions. Bioinformatics 2019 35 20 4200 4202 10.1093/bioinformatics/btz210 30903160
    [Google Scholar]
  37. Yoshihara K. Shahmoradgoli M. Martínez E. Vegesna R. Kim H. Torres-Garcia W. Treviño V. Shen H. Laird P.W. Levine D.A. Carter S.L. Getz G. Stemke-Hale K. Mills G.B. Verhaak R.G.W. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 2013 4 1 2612 10.1038/ncomms3612 24113773
    [Google Scholar]
  38. Newman A.M. Liu C.L. Green M.R. Gentles A.J. Feng W. Xu Y. Hoang C.D. Diehn M. Alizadeh A.A. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 2015 12 5 453 457 10.1038/nmeth.3337 25822800
    [Google Scholar]
  39. Reinhold W.C. Sunshine M. Liu H. Varma S. Kohn K.W. Morris J. Doroshow J. Pommier Y. CellMiner: a web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set. Cancer Res. 2012 72 14 3499 3511 10.1158/0008‑5472.CAN‑12‑1370 22802077
    [Google Scholar]
  40. Saikia S. Bordoloi M. Molecular docking: Challenges, advances and its use in drug discovery perspective. Curr. Drug Targets 2019 20 5 501 521 10.2174/1389450119666181022153016 30360733
    [Google Scholar]
  41. Schiffrin B. Radford S.E. Brockwell D.J. Calabrese A.N. PyXlinkViewer : A flexible tool for visualization of protein chemical crosslinking data within the PyMOL molecular graphics system. Protein Sci. 2020 29 8 1851 1857 10.1002/pro.3902 32557917
    [Google Scholar]
  42. Qian X. Bao Z.M. Yao D. Shi Y. Lysine demethylase 5C epigenetically reduces transcription of ITIH1 that results in augmented progression of liver hepatocellular carcinoma. Kaohsiung J. Med. Sci. 2022 38 5 437 446 10.1002/kjm2.12501 35080113
    [Google Scholar]
  43. Liao Z. Zhang H. Liu F. Wang W. Liu Y. Su C. Zhu H. Chen X. Zhang B. Zhang Z. m 6 A-dependent ITIH1 regulated by TGF-β acts as a target for hepatocellular carcinoma progression. Adv. Sci. (Weinh.) 2024 11 42 2401013 10.1002/advs.202401013 39234824
    [Google Scholar]
  44. Liu Y. Shi L. Yuan C. Feng Y. Li M. Liu H. Chen X. Yao D. Wang Q. Downregulation of ITIH3 contributes to cisplatin-based chemotherapy resistance in ovarian carcinoma via the Bcl-2 mediated anti-apoptosis signaling pathway. Oncol. Lett. 2022 25 2 61 10.3892/ol.2022.13646 36644154
    [Google Scholar]
  45. Chong P.K. Lee H. Zhou J. Liu S.C. Loh M.C.S. Wang T.T. Chan S.P. Smoot D.T. Ashktorab H. So J.B.Y. Lim K.H. Yeoh K.G. Lim Y.P. ITIH3 is a potential biomarker for early detection of gastric cancer. J. Proteome Res. 2010 9 7 3671 3679 10.1021/pr100192h 20515073
    [Google Scholar]
  46. van den Broek I. Sparidans R.W. van Winden A.W.J. Gast M.C.W. van Dulken E.J. Schellens J.H.M. Beijnen J.H. The absolute quantification of eight inter-α-trypsin inhibitor heavy chain 4 (ITIH 4 )-derived peptides in serum from breast cancer patients. Proteomics Clin. Appl. 2010 4 12 931 939 10.1002/prca.201000035 21137033
    [Google Scholar]
  47. Zhao Y. Shen H. Wu J. Yu J. Yuan Y. Zhong C. Discovery, identification and mechanism of chemosensitivity-relate biomarker inter-α-trypsin inhibitor heavy chain 4 in metastatic colorectal cancer. Heliyon 2024 10 13 e33571 10.1016/j.heliyon.2024.e33571 39040328
    [Google Scholar]
  48. Weidle U.H. Birzele F. Tiefenthaler G. Potential of protein-based anti-metastatic therapy with serpins and inter α-trypsin inhibitors. Cancer Genomics Proteomics 2018 15 4 225 238 10.21873/cgp.20081 29976628
    [Google Scholar]
  49. Daum A.K. Dittmann J. Jansen L. Peters S. Dahmen U. Heger J.I. Hoppe-Seyler F. Gille A. Clement J.H. Runnebaum I.B. Dürst M. Backsch C. ITIH5 shows tumor suppressive properties in cervical cancer cells grown as multicellular tumor spheroids. Am. J. Transl. Res. 2021 13 9 10298 10314 34650698
    [Google Scholar]
  50. Liu J. Cao F. Li X. Zhang L. Liu Z. Li X. Lin J. Han C. ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4. Cell Death Dis. 2021 12 5 438 10.1038/s41419‑021‑03707‑7 33935281
    [Google Scholar]
  51. Young E.D. Manley S.J. Beadnell T.C. Shearin A.E. Sasaki K. Zimmerman R. Kauffman E. Vivian C.J. Parasuram A. Iwakuma T. Grandgenett P.M. Hollingsworth M.A. O’Neil M. Welch D.R. Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5. Br. J. Cancer 2021 124 1 166 175 10.1038/s41416‑020‑01093‑z 33024269
    [Google Scholar]
  52. Enghild J.J. Salvesen G. Hefta S.A. Thøgersen I.B. Rutherfurd S. Pizzo S.V. Chondroitin 4-sulfate covalently cross-links the chains of the human blood protein pre-alpha-inhibitor. JBC 1991 266 2 747 10.1016/S0021‑9258(17)35235‑3
    [Google Scholar]
  53. Veeck J. Chorovicer M. Naami A. Breuer E. Zafrakas M. Bektas N. Dürst M. Kristiansen G. Wild P.J. Hartmann A. Knuechel R. Dahl E. The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation. Oncogene 2008 27 6 865 876 10.1038/sj.onc.1210669 17653090
    [Google Scholar]
  54. Jiang X. Bai X.-Y. Li B. Li Y. Xia K. Wang M. Li S. Wu H. Plasma inter-alpha-trypsin inhibitor heavy chains H3 and H4 serve as novel diagnostic biomarkers in human colorectal cancer. Dis Markers. 2019 2019 5069614 10.1155/2019/5069614
    [Google Scholar]
  55. Werbowetski-Ogilvie T.E. Agar N.Y.R. Waldkircher de Oliveira R.M. Faury D. Antel J.P. Jabado N. Del Maestro R.F. Isolation of a natural inhibitor of human malignant glial cell invasion: inter α-trypsin inhibitor heavy chain 2. Cancer Res. 2006 66 3 1464 1472 10.1158/0008‑5472.CAN‑05‑1913 16452202
    [Google Scholar]
  56. Tanaka Y. Kobayashi H. Suzuki M. Kanayama N. Suzuki M. Terao T. Upregulation of bikunin in tumor-infiltrating macrophages as a factor of favorable prognosis in ovarian cancer. Gynecol. Oncol. 2004 94 3 725 734 10.1016/j.ygyno.2004.06.012 15350365
    [Google Scholar]
  57. Tanaka Y. Kobayashi H. Suzuki M. Reduced bikunin gene expression as a factor of poor prognosis in ovarian carcinoma. Cancer 2003 98 2 424 10.1002/cncr.11506
    [Google Scholar]
  58. Kanayama N. El Maradny E. Halim A. Liping S. Maehara K. Kajiwara Y. Terao T. Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of Ca++ influx. Am. J. Obstet. Gynecol. 1995 173 1 192 199 10.1016/0002‑9378(95)90189‑2 7631679
    [Google Scholar]
  59. El Maradny E. Kanayama N. Halim A. Maehara K. Kobayashi T. Terao T. Effects of urinary trypsin inhibitor on myometrial contraction in term and preterm deliveries. Gynecol. Obstet. Invest. 1996 41 2 96 102 10.1159/000292051 8838968
    [Google Scholar]
  60. Park J. Cha D.H. Lee S.J. Kim Y.N. Kim Y.H. Kim K.P. Discovery of the serum biomarker proteins in severe preeclampsia by proteomic analysis. Exp. Mol. Med. 2011 43 7 427 435 10.3858/emm.2011.43.7.047 21646846
    [Google Scholar]
  61. van den Berg C.B. Duvekot J.J. Güzel C. Hansson S.R. de Leeuw T.G. Steegers E.A.P. Versendaal J. Luider T.M. Stoop M.P. Elevated levels of protein AMBP in cerebrospinal fluid of women with preeclampsia compared to normotensive pregnant women. Proteomics Clin. Appl. 2017 11 1-2 1600082 10.1002/prca.201600082 27615121
    [Google Scholar]
  62. Li J. Liu G. Lentiviral injection of inter-α-trypsin inhibitor heavy chain 4 promotes female spinal cord injury mice recuperation by diminishing peripheral and central inflammation. Inflammation 2024 10.1007/s10753‑024‑02196‑y 39648260
    [Google Scholar]
  63. Singh K. Zhang L.X. Bendelja K. Heath R. Murphy S. Sharma S. Padbury J.F. Lim Y.P. Inter-alpha inhibitor protein administration improves survival from neonatal sepsis in mice. Pediatr. Res. 2010 68 3 242 247 10.1203/PDR.0b013e3181e9fdf0 20520583
    [Google Scholar]
  64. Opal S.M. Lim Y.P. Cristofaro P. Artenstein A.W. Kessimian N. DelSesto D. Parejo N. Palardy J.E. Siryaporn E. Inter-α inhibitor proteins: A novel therapeutic strategy for experimental anthrax infection. Shock 2011 35 1 42 44 10.1097/SHK.0b013e3181e83204 20523269
    [Google Scholar]
  65. Zhang X. Zhu Z. Jiao W. Liu W. Liu F. Zhu X. Ulinastatin treatment for acute respiratory distress syndrome in China: A meta-analysis of randomized controlled trials. BMC Pulm. Med. 2019 19 1 196 10.1186/s12890‑019‑0968‑6 31684936
    [Google Scholar]
  66. Wang H. Liu B. Tang Y. Chang P. Yao L. Huang B. Lodato R.F. Liu Z. Improvement of Sepsis prognosis by ulinastatin: A systematic review and meta-analysis of randomized controlled trials. Front. Pharmacol. 2019 10 1370 10.3389/fphar.2019.01370 31849646
    [Google Scholar]
  67. Balduyck M. Albani D. Jourdain M. Mizon C. Tournoys A. Drobecq H. Fourrier F. Mizon J. Inflammation-induced systemic proteolysis of inter-α-inhibitor in plasma from patients with sepsis. J. Lab. Clin. Med. 2000 135 2 188 198 10.1067/mlc.2000.104462 10695665
    [Google Scholar]
  68. Zhou X. Xue F. Li T. Xue J. Yue S. Zhao S. Lu H. He C. Exploration of potential biomarkers for early bladder cancer based on urine proteomics. Front. Oncol. 2024 14 1309842 10.3389/fonc.2024.1309842 38410113
    [Google Scholar]
  69. Zhang X. Zhang X. Guo L. Bai Y. Tian Y. Luo H. The function of the inter-alpha-trypsin inhibitors in the development of disease. Front. Med. (Lausanne) 2024 11 1432224 10.3389/fmed.2024.1432224 39149600
    [Google Scholar]
  70. Gao J. Yu G. Yan Y. Hu W. Hu D. Wang W. Yang G. Wei J. Yang S. ITIH1 suppresses carcinogenesis in renal cell carcinoma through regulation of the NF-κB signaling pathway. Exp. Ther. Med. 2024 28 3 368 10.3892/etm.2024.12657 39091412
    [Google Scholar]
  71. Pihl R. Jensen R.K. Poulsen E.C. Jensen L. Hansen A.G. Thøgersen I.B. Dobó J. Gál P. Andersen G.R. Enghild J.J. Thiel S. ITIH4 acts as a protease inhibitor by a novel inhibitory mechanism. Sci. Adv. 2021 7 2 eaba7381 10.1126/sciadv.aba7381 33523981
    [Google Scholar]
  72. Sun Y. Jin J. Jing H. Lu Y. Zhu Q. Shu C. Zhang Q. Jing D. ITIH4 is a novel serum biomarker for early gastric cancer diagnosis. Clin. Chim. Acta 2021 523 365 373 10.1016/j.cca.2021.10.022 34687700
    [Google Scholar]
  73. e Silva L.S. Jordão P.H.F. Balieiro B.C. Baracioli L.S. de Nóbrega D.F. Novais A.A. Chuffa L.G.A. Zuccari D.A.P.C. Immunohistochemical analysis of inter-alpha-trypsin inhibitor heavy chain 2 and enolase 1 in canine mammary tumors: Associations with tumor aggressiveness and prognostic significance. Vet. Sci. 2025 12 2 110 10.3390/vetsci12020110 40005870
    [Google Scholar]
  74. Novais A.A. Tamarindo G.H. Melo L.M.M. Balieiro B.C. Nóbrega D. dos Santos G. Saldanha S.F. de Souza F.F. Chuffa L.G.A. Bracha S. Zuccari D.A.P.C. Exploring canine mammary cancer through liquid biopsy: Proteomic profiling of small extracellular vesicles. Cancers 2024 16 14 2562 10.3390/cancers16142562 39061201
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673375809250730142009
Loading
A Comprehensive Analysis of the ITIH Family Across Multiple Cancer Types and an Initial Investigation of ITIH1 in Gastric Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0109298673375809250730142009
/content/journals/cmc/10.2174/0109298673375809250730142009
/content/journals/cmc/10.2174/0109298673375809250730142009
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: ITIH1 ; pan-cancer ; Gastric cancer ; ITIH family ; molecular docking ; GEO

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test