Skip to content
2000
Volume 20, Issue 5
  • ISSN: 1574-8928
  • E-ISSN: 2212-3970

Abstract

Background

The precise function of Tolloid Like 2 (TLL2) remains uncertain within the context of Lung Adenocarcinoma (LUAD).

Objectives

The primary objective of this investigation was to conduct a thorough analysis.

Methods

To assess its diagnostic utility, data from The Cancer Genome Atlas (TCGA) database were used to assess TLL2 expression in pan-cancer and LUAD. The study has also investigated the correlation between TLL2 expression levels and LUAD symptoms and prognosis. Furthermore, the study has explored possible regulatory networks involving TLL2, including its association with immune infiltration, tumor stemness index (mRNAsi), and drug sensitivity in LUAD. We have explored TLL2 expression in single-cell sequencing of LUAD and the genomic variation and clinical significance of TLL2 in LUAD. The expression of TLL2 has been validated in GSE87340 and cell lines by quantitative Real-time PCR (qRT-PCR).

Results

An abnormal expression of TLL2 has been found in pan-cancer and LUAD. In LUAD patients, elevated levels of TLL2 were significantly related to the T stage ( = 0.046) and the pathological stage ( = 0.016). The expression of TLL2 in patients with LUAD was significantly associated with poorer Overall Survival (OS) ( < 0.001). The expression of TLL2 was determined to be an independent predictor of poorer OS ( = 0.042). TLL2 was associated with ribosome, neuroactive ligand-receptor interaction, allograft rejection, ECM receptor interaction, asthma, porphyrin and chlorophyll metabolism, focal adhesion, pentose and glucuronate inter-conversions, and ascorbate and aldarate metabolism. The expression of TLL2 in LUAD was correlated with immune infiltration and mRNAsi. The expression of TLL2 was significantly and negatively correlated with TAK-715, XMD13-2, STF-62247, OSI-930, and EHT-1864 in LUAD. The TLL2 gene was up-regulated in multiple individual LUAD cells. LUAD patients with altered TLL2 had a shorter PFS as opposed to those with unaltered TLL2. The expression of TLL2 was significantly increased in LUAD cells.

Conclusion

For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker.

Loading

Article metrics loading...

/content/journals/pra/10.2174/0115748928303392240817131807
2024-08-26
2025-12-05
Loading full text...

Full text loading...

References

  1. MolinaJ.R. YangP. CassiviS.D. SchildS.E. AdjeiA.A. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship.Mayo Clin. Proc.200883558459410.1016/S0025‑6196(11)60735‑018452692
    [Google Scholar]
  2. ChenZ. FillmoreC.M. HammermanP.S. KimC.F. WongK.K. Non-small-cell lung cancers: a heterogeneous set of diseases.Nat. Rev. Cancer201414853554610.1038/nrc377525056707
    [Google Scholar]
  3. Del MastroL. CeppiM. PoggioF. BighinC. PeccatoriF. DemeestereI. LevaggiA. GiraudiS. LambertiniM. D’AlonzoA. CanaveseG. PronzatoP. BruzziP. Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: Systematic review and meta-analysis of randomized trials.Cancer Treat. Rev.201440567568310.1016/j.ctrv.2013.12.00124360817
    [Google Scholar]
  4. de PerrotM. FadelE. MussotS. de PalmaA. ChapelierA. DartevelleP. Resection of locally advanced (T4) non-small cell lung cancer with cardiopulmonary bypass.Ann. Thorac. Surg.20057951691169610.1016/j.athoracsur.2004.10.02815854956
    [Google Scholar]
  5. MollicaV. RizzoA. MarchettiA. TateoV. TassinariE. RoselliniM. MassafraR. SantoniM. MassariF. The impact of ECOG performance status on efficacy of immunotherapy and immune-based combinations in cancer patients: the MOUSEION-06 study.Clin. Exp. Med.20232385039504910.1007/s10238‑023‑01159‑137535194
    [Google Scholar]
  6. RizzoA. Identifying optimal first-line treatment for advanced non-small cell lung carcinoma with high PD-L1 expression: a matter of debate.Br. J. Cancer202212781381138210.1038/s41416‑022‑01929‑w36064585
    [Google Scholar]
  7. Dall’OlioF.G. RizzoA. MollicaV. MassucciM. MaggioI. MassariF. Immortal time bias in the association between toxicity and response for immune checkpoint inhibitors: a meta-analysis.Immunotherapy202113325727010.2217/imt‑2020‑017933225800
    [Google Scholar]
  8. RizzoA. CusmaiA. GiovannelliF. AcquafreddaS. RinaldiL. MisinoA. MontagnaE.S. UngaroV. LorussoM. PalmiottiG. Impact of Proton Pump Inhibitors and Histamine-2-Receptor Antagonists on Non-Small Cell Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis.Cancers2022146140410.3390/cancers1406140435326555
    [Google Scholar]
  9. WuH. ZhouJ. MeiS. WuD. MuZ. ChenB. XieY. YeY. LiuJ. Circulating exosomal microRNA‐96 promotes cell proliferation, migration and drug resistance by targeting LMO7.J. Cell. Mol. Med.20172161228123610.1111/jcmm.1305628026121
    [Google Scholar]
  10. XuY. WangY. LiuH. ShiQ. ZhuD. AmosC.I. FangS. LeeJ.E. HyslopT. LiX. HanJ. WeiQ. Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival.Mol. Carcinog.2018571223110.1002/mc.2271628796414
    [Google Scholar]
  11. SuL. QiaoY. LuoJ. HuangR. XiaoY. Exome and Sputum Microbiota as Predictive Markers of Frequent Exacerbations in Chronic Obstructive Pulmonary Disease.Biomolecules20221210148110.3390/biom1210148136291689
    [Google Scholar]
  12. LiuL. ChenJ. LiJ. YangY. ZengX. TianX. Whole Exome Sequencing Revealed Variants That Predict Pulmonary Artery Involvement in Patients with Takayasu Arteritis.J. Inflamm. Res.2022154817483110.2147/JIR.S37740236046661
    [Google Scholar]
  13. GalaninaN. GoodmanA.M. CohenP.R. FramptonG.M. KurzrockR. Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade.Cancer Immunol. Res.20186101129113510.1158/2326‑6066.CIR‑18‑012130194084
    [Google Scholar]
  14. YangD. LiuM. JiangJ. LuoY. WangY. ChenH. LiD. WangD. YangZ. ChenH. Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma.Cancers20221424622010.3390/cancers1424622036551704
    [Google Scholar]
  15. YiW. ShenH. SunD. XuY. FengY. LiD. WangC. Low Expression of Long Noncoding RNA SLC26A4 Antisense RNA 1 Is an Independent Prognostic Biomarker and Correlate of Immune Infiltrates in Breast Cancer.Med. Sci. Monit.202127e93452234880202
    [Google Scholar]
  16. MiaoL. JingL. ChenB. ZengT. ChenY. TPD52 is a Potential Prognostic Biomarker and Correlated with Immune Infiltration: A Pan-cancer Analysis.Curr. Mol. Med.202338178662
    [Google Scholar]
  17. MiaoL. ChenB. JingL. ZengT. ChenY. TPD52 as a Potential Prognostic Biomarker and its Correlation with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma: Bioinformatic Analysis and Experimental Verification.Recent Patents Anticancer Drug Discov.20241911838305309
    [Google Scholar]
  18. VivianJ. RaoA.A. NothaftF.A. KetchumC. ArmstrongJ. NovakA. PfeilJ. NarkizianJ. DeranA.D. Musselman-BrownA. SchmidtH. AmstutzP. CraftB. GoldmanM. RosenbloomK. ClineM. O’ConnorB. HannaM. BirgerC. KentW.J. PattersonD.A. JosephA.D. ZhuJ. ZaranekS. GetzG. HausslerD. PatenB. Toil enables reproducible, open source, big biomedical data analyses.Nat. Biotechnol.201735431431610.1038/nbt.377228398314
    [Google Scholar]
  19. ChenJ. TangH. LiT. JiangK. ZhongH. WuY. HeJ. LiD. LiM. CaiX. Comprehensive Analysis of the Expression, Prognosis, and Biological Significance of OVOLs in Breast Cancer.Int. J. Gen. Med.2021143951396010.2147/IJGM.S32640234345183
    [Google Scholar]
  20. ZhangJ. KuangP. WanF. ZhangY. ZhangW. ZhangX. Effects of CLDN9 on Proliferation of Uterine Corpus Endometrioid Carcinoma Cells202313614210.1145/3608164.3608183
    [Google Scholar]
  21. ChenY. XuH. TangH. LiH. ZhangC. JinS. BaiD. miR-9-5p expression is associated with vascular invasion and prognosis in hepatocellular carcinoma, and in vitro verification.J. Cancer Res. Clin. Oncol.202314916146571467110.1007/s00432‑023‑05257‑137584711
    [Google Scholar]
  22. LiangW. LuY. PanX. ZengY. ZhengW. LiY. NieY. LiD. WangD. Decreased Expression of a Novel lncRNA FAM181A-AS1 is Associated with Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma.Pharm. Genomics Pers. Med.20221598599810.2147/PGPM.S38490136482943
    [Google Scholar]
  23. LinZ. HuangW. YiY. LiD. XieZ. LiZ. YeM. LncRNA ADAMTS9-AS2 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Lung Adenocarcinoma.Int. J. Gen. Med.2021148541855510.2147/IJGM.S34068334849000
    [Google Scholar]
  24. BindeaG. MlecnikB. TosoliniM. KirilovskyA. WaldnerM. ObenaufA.C. AngellH. FredriksenT. LafontaineL. BergerA. BrunevalP. FridmanW.H. BeckerC. PagèsF. SpeicherM.R. TrajanoskiZ. GalonJ. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.Immunity201339478279510.1016/j.immuni.2013.10.00324138885
    [Google Scholar]
  25. LiuT. WuH. WeiJ. The Construction and Validation of a Novel Ferroptosis-Related Gene Signature in Parkinson’s Disease.Int. J. Mol. Sci.202324241720310.3390/ijms24241720338139032
    [Google Scholar]
  26. YuanH. JiangT. ZhangW.D. YangZ. LuoS. WangX. ZhuX. QiS. MahmmodY.S. ZhangX.X. YuanZ.G. Multiomics and bioinformatics identify differentially expressed effectors in the brain of Toxoplasma gondii infected masked palm civet.Front. Cell. Infect. Microbiol.202313126762910.3389/fcimb.2023.126762937818043
    [Google Scholar]
  27. ChenB. LuX. ZhouQ. ChenQ. ZhuS. LiG. LiuH. PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer.PLoS One2023188e029003110.1371/journal.pone.029003137582104
    [Google Scholar]
  28. LuZ.M. PanS.L. YuanW.L. FengJ.L. TianD. ShangX.Q. Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer.Medicine202310250e3648010.1097/MD.000000000003648038115316
    [Google Scholar]
  29. DuQ. XingN. GuoS. MengX. ZhangY. WangS. Cycas revoluta leaves: As a potential flavonoids source for targeted regulation of immune-related markers in lung adenocarcinoma.Ind. Crops Prod.202320211696710.1016/j.indcrop.2023.116967
    [Google Scholar]
  30. YoshiharaK. ShahmoradgoliM. MartínezE. VegesnaR. KimH. Torres-GarciaW. TreviñoV. ShenH. LairdP.W. LevineD.A. CarterS.L. GetzG. Stemke-HaleK. MillsG.B. VerhaakR.G.W. Inferring tumour purity and stromal and immune cell admixture from expression data.Nat. Commun.201341261210.1038/ncomms361224113773
    [Google Scholar]
  31. XuF. ZhanX. ZhengX. XuH. LiY. HuangX. LinL. ChenY. A signature of immune-related gene pairs predicts oncologic outcomes and response to immunotherapy in lung adenocarcinoma.Genomics202011264675468310.1016/j.ygeno.2020.08.01432798715
    [Google Scholar]
  32. YinY. ChenJ. ChenQ. HeH. ZhuN. XiaP. YuC. MengL. Differential expression of zinc finger CCHC-type superfamily proteins in thyroid carcinoma and their associations with tumor immunity.Thyroid Res.20231614210.1186/s13044‑023‑00185‑137848968
    [Google Scholar]
  33. LiJ. LiL. DongY. ZhongB. YinW. Comprehensive Analysis of Cuproptosis Genes and Identification of Cuproptosis Subtypes in Breast Cancer.Comb. Chem. High Throughput Screen.20232681578159310.2174/138620732666623012011290436683372
    [Google Scholar]
  34. LiL. TangC. YeJ. XuD. ChuC. WangL. ZhouQ. GanS. LiuB. Bioinformatic analysis of m6A “reader” YTH family in pan-cancer as a clinical prognosis biomarker.Sci. Rep.20231311735010.1038/s41598‑023‑44143‑137833468
    [Google Scholar]
  35. DongL. LiY. LiuL. MengX. LiS. HanD. XiaoZ. XiaQ. Smurf1 suppression enhances temozolomide chemosensitivity in glioblastoma by facilitating PTEN Nuclear Translocation.Cells20221120330210.3390/cells1120330236291166
    [Google Scholar]
  36. ZhangK. YangW. ZhangZ. MaK. LiL. XuY. QiuJ. YuC. ZhouJ. CaiL. GongY. GongK. A Novel Cuproptosis-Related Prognostic Model and the Hub Gene FDX1 Predict the Prognosis and Correlate with Immune Infiltration in Clear Cell Renal Cell Carcinoma.J. Oncol.2022202211910.1155/2022/212408836536785
    [Google Scholar]
  37. ChenM. LiS. LiangY. ZhangY. LuoD. WangW. Integrative Multi-Omics Analysis of Identified NUF2 as a Candidate Oncogene Correlates With Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer.Front. Oncol.20211165650910.3389/fonc.2021.65650934178642
    [Google Scholar]
  38. LiS. LiuY. YaoC. XuA. ZengX. GeY. ShengX. ZhangH. ZhouX. LongY. Prognostic prediction and expression validation of NSD3 in pan-cancer analyses.Biocell20234751003101910.32604/biocell.2023.027209
    [Google Scholar]
  39. LinZ. HuangW. XieZ. YiY. LiZ. Expression, Clinical Significance, Immune Infiltration, and Regulation Network of miR-3940-5p in Lung Adenocarcinoma Based on Bioinformatic Analysis and Experimental Validation.Int. J. Gen. Med.2022156451646410.2147/IJGM.S37576135966511
    [Google Scholar]
  40. SunC. GaoW. LiuJ. ChengH. HaoJ. FGL1 regulates acquired resistance to Gefitinib by inhibiting apoptosis in non-small cell lung cancer.Respir. Res.202021121010.1186/s12931‑020‑01477‑y32778129
    [Google Scholar]
  41. LuX. LiG. LiuS. WangH. ChenB. MiR-585-3p suppresses tumor proliferation and migration by directly targeting CAPN9 in high grade serous ovarian cancer.J. Ovarian Res.20211419010.1186/s13048‑021‑00841‑w34238324
    [Google Scholar]
  42. HandzlikG SzymańskaE PękalaE KędzierskiL StrzałkowskaD DuławaJ Low-sodium dietary approach in the management of resistant and refractory hypertension: preliminary results.Polish archives of internal medicine20211311010.20452/pamw.16098
    [Google Scholar]
  43. ZhangY. ZhouY. WeiF. circABCB10 Promotes Malignant Progression of Gastric Cancer Cells by Preventing the Degradation of MYC.J. Oncol.2021202111410.1155/2021/462503334950208
    [Google Scholar]
  44. PintoA SorrentinoR Methods and kits for the diagnosis of lung cancer.US202303414032023
  45. ChengT ZhouN Prognostic markers in lung cancer, prognostic typing model of lung cancer, and application thereof.US202201198892022
  46. AhnMJ LeeHO KimNY Biomarker panel for determining molecular subtype of lung cancer, and use thereof.US202103884502021
  47. KimHK HongSH ParkY ChoiYH ParkJH ChoiBH Marker composition for diagnosing or predicting prognosis of lung cancer based on exosome overexpressing gcc2 gene or protein.US202201966642022
  48. JablonsDM RazDJ multigene prognostic assay for lung cancer.US202003779572020
  49. ZhangY. ZhangT. ZhaoY. WuH. ZhenQ. ZhuS. HouS. Lactate dehydrogenase D serves as a novel biomarker for prognosis and immune infiltration in lung adenocarcinoma.BMC Cancer202323175910.1186/s12885‑023‑11221‑637587457
    [Google Scholar]
  50. ZhangY. ShengH. FuY. ChenL. Transcription Factor FOXA1 Facilitates Glycolysis and Proliferation of Lung Adenocarcinoma via Activation of TEX19.Mol. Biotechnol.202310.1007/s12033‑023‑00848‑237606876
    [Google Scholar]
  51. WuZ. ZhuoT. LiZ. ZhuY. WuJ. LiangG. DaiL. WangY. TanX. ChenM. High SGO2 predicted poor prognosis and high therapeutic value of lung adenocarcinoma and promoted cell proliferation, migration, invasion, and epithelial-to-mesenchymal transformation.J. Cancer202314122301231410.7150/jca.8628537576392
    [Google Scholar]
  52. WangY. YeD. LiY. LvF. ShenW. LiH. TianL. FanZ. LiY. wangY. LiF. ChenY. Prognostic and immune infiltrative biomarkers of CENPO in pan–cancer and its relationship with lung adenocarcinoma cell proliferation and metastasis.BMC Cancer202323173510.1186/s12885‑023‑11233‑237558987
    [Google Scholar]
  53. WangX. ZhaoB. RenD. HuX. QiaoJ. ZhangD. ZhangY. PanY. FanY. LiuL. WangX. MaH. JiaX. SongS. ZhaoC. LiuJ. WangL. Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis.Cancer Biomark.202338219120110.3233/CBM‑23013737545227
    [Google Scholar]
  54. WangZ. LiZ. ZhouK. WangC. JiangL. ZhangL. YangY. LuoW. QiaoW. WangG. NiY. DaiS. GuoT. JiG. XuM. LiuY. SuZ. CheG. LiW. Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing.Nat. Commun.2021121650010.1038/s41467‑021‑26770‑234764257
    [Google Scholar]
  55. ParkerA.L. BowmanE. ZingoneA. RyanB.M. CooperW.A. Kohonen-CorishM. HarrisC.C. CoxT.R. Extracellular matrix profiles determine risk and prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma.Genome Med.202214112610.1186/s13073‑022‑01127‑636404344
    [Google Scholar]
  56. García SanzMT González BarcalaFJ Alvarez DobañoJM Valdés CuadradoL Asthma and risk of lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2011131072873010.1007/s12094‑011‑0723‑9
    [Google Scholar]
  57. CharokoposA. BramanS.S. BrownS.A.W. MhangoG. de-TorresJ.P. ZuluetaJ.J. SharmaS. HolguinF. SigelK.M. PowellC.A. FedermanA.D. WisniveskyJ.P. Lung Cancer Risk among Patients with Asthma–Chronic Obstructive Pulmonary Disease Overlap.Ann. Am. Thorac. Soc.202118111894190010.1513/AnnalsATS.202010‑1280OC34019783
    [Google Scholar]
  58. DyG.K. The role of focal adhesion kinase in lung cancer.Anticancer. Agents Med. Chem.201313458158310.2174/187152061131304000722934708
    [Google Scholar]
  59. MunroM.J. WickremesekeraS.K. PengL. TanS.T. ItinteangT. Cancer stem cells in colorectal cancer: a review.J. Clin. Pathol.201871211011610.1136/jclinpath‑2017‑20473928942428
    [Google Scholar]
  60. WangL. LiuW. LiuJ. WangY. TaiJ. YinX. TanJ. Identification of Immune-Related Therapeutically Relevant Biomarkers in Breast Cancer and Breast Cancer Stem Cells by Transcriptome-Wide Analysis: A Clinical Prospective Study.Front. Oncol.20211055413810.3389/fonc.2020.55413833718103
    [Google Scholar]
  61. CuiP. LiuW. ZhaoY. LinQ. ZhangD. DingF. XinC. ZhangZ. SongS. SunF. YuJ. HuS. Comparative analyses of H3K4 and H3K27 trimethylations between the mouse cerebrum and testis.Genomics Proteomics Bioinformatics2012102829310.1016/j.gpb.2012.05.00722768982
    [Google Scholar]
/content/journals/pra/10.2174/0115748928303392240817131807
Loading
/content/journals/pra/10.2174/0115748928303392240817131807
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): drug sensitivity; immune infiltration; Lung adenocarcinoma; mRNAsi; prognosis; TLL2
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