Skip to content
2000
Volume 33, Issue 4
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

The role of solute carrier family 6 member 17 (SLC6A17) in lung adenocarcinoma (LUAD) is unclear.

Objectives

To address this gap in knowledge, we employed bioinformatics analysis and experimental validation.

Methods

This research aimed to scrutinize the expression patterns of the SLC6A17 gene across a spectrum of cancers and specifically within LUAD, utilizing data extracted from The Cancer Genome Atlas (TCGA). The correlation between SLC6A17 expression and LUAD prognosis was investigated to assess its diagnostic relevance. The study delved into the possible regulatory mechanisms of SLC6A17, focusing on its links to immune cell infiltration and drug response in LUAD. The examination of SLC6A17 expression was extended to single-cell sequencing data in LUAD, alongside an evaluation of the gene's genomic alterations and clinical implications within this disease context. Validation of SLC6A17 expression levels was conducted using datasets from GSE87340 and various cell lines, employing quantitative real-time polymerase chain reaction (qRT-PCR) techniques.

Results

SLC6A17 exhibited aberrant expression in both pan-cancer and LUAD. Increased expression of SLC6A17 in LUAD patients was significantly associated with poorer overall survival ( = 0.008), progress-free survival ( = 0.019), and disease specific survival ( = 0.030). In LUAD patients, the levels of SLC6A17 expression were found to be a significant standalone indicator of prognosis, with a -value of 0.031. SLC6A17 exhibited associations with various pathways, including focal adhesion, ECM receptor interaction, cell cycle, linoleic acid metabolism, pathways in cancer, and more. SLC6A17 expression demonstrated correlations with immune infiltration in LUAD. SLC6A17 expression revealed a notably inverse relationship with several substances, including AR-42, T0901317, tubastatin A, SB52334, and amuvatinib, within the context of LUAD. SLC6A17 was found to be significantly positively regulated in LUAD cell lines.

Conclusion

These findings suggest that SLC6A17 indicates the potential of a potential prognostic biomarker and immunotherapeutic target for patients with LUAD.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673344310241216042749
2025-01-03
2026-02-21
Loading full text...

Full text loading...

References

  1. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
    [Google Scholar]
  2. ThaiA.A. SolomonB.J. SequistL.V. GainorJ.F. HeistR.S. Lung cancer.Lancet20213981029953555410.1016/S0140‑6736(21)00312‑334273294
    [Google Scholar]
  3. TanL. ZhangH. DingY. HuangY. SunD. CRTAC1 identified as a promising diagnosis and prognostic biomarker in lung adenocarcinoma.Sci. Rep.20241411122310.1038/s41598‑024‑61804‑x38755183
    [Google Scholar]
  4. KulawikD.J. TrojnarA. Lung cancer in women in 21th century.J. Thorac. Dis.20201284398441010.21037/jtd‑20‑28732944353
    [Google Scholar]
  5. HirschF.R. ScagliottiG.V. MulshineJ.L. KwonR. CurranW.J.Jr WuY.L. AresP.L. Lung cancer: Current therapies and new targeted treatments.Lancet20173891006629931110.1016/S0140‑6736(16)30958‑827574741
    [Google Scholar]
  6. XuM. YangM. DDX52 gene expression in LUAD tissues indicates potential as a prognostic biomarker and therapeutic target.Sci. Rep.20231311743410.1038/s41598‑023‑44347‑537833424
    [Google Scholar]
  7. EttingerD.S. WoodD.E. AisnerD.L. AkerleyW. BaumanJ.R. BharatA. BrunoD.S. ChangJ.Y. ChirieacL.R. D’AmicoT.A. DillingT.J. DowellJ. GettingerS. GubensM.A. HegdeA. HennonM. LacknerR.P. LanutiM. LealT.A. LinJ. LooB.W.Jr LovlyC.M. MartinsR.G. MassarelliE. MorgenszternD. NgT. OttersonG.A. PatelS.P. RielyG.J. SchildS.E. ShapiroT.A. SinghA.P. StevensonJ. TamA. YanagawaJ. YangS.C. GregoryK.M. HughesM. NCCN guidelines insights: Non–small cell lung cancer, version 2.2021.J. Natl. Compr. Canc. Netw.202119325426610.6004/jnccn.2021.001333668021
    [Google Scholar]
  8. JiaX. ZhuJ. BianX. LiuS. YuS. LiangW. JiangL. MaoR. ZhangW. RaoY. Importance of glutamine in synaptic vesicles revealed by functional studies of SLC6A17 and its mutations pathogenic for intellectual disability.eLife202312RP8697210.7554/eLife.8697237440432
    [Google Scholar]
  9. WaltlS. Mutations in SLC6A17 cause autosomal-recessive intellectual disability.Clin. Genet.201588213613710.1111/cge.1261025970702
    [Google Scholar]
  10. ParraL.A. BaustT. MestikawyE.S. QuirozM. HoffmanB. HaflettJ.M. YaoJ.K. TorresG.E. The orphan transporter Rxt1/NTT4 (SLC6A17) functions as a synaptic vesicle amino acid transporter selective for proline, glycine, leucine, and alanine.Mol. Pharmacol.20087461521153210.1124/mol.108.05000518768736
    [Google Scholar]
  11. ZaiaK.A. ReimerR.J. Synaptic vesicle protein NTT4/XT1 (SLC6A17) catalyzes Na+-coupled neutral amino acid transport.J. Biol. Chem.2009284138439844810.1074/jbc.M80640720019147495
    [Google Scholar]
  12. ZhangY. YangL. JiaoX. Analysis of breast cancer differences between China and western countries based on radiogenomics.Genes20221312241610.3390/genes1312241636553681
    [Google Scholar]
  13. 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]
  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. ZhaoX. LuM. LiuZ. ZhangM. YuanH. DanZ. WangD. MaB. YangY. YangF. SunR. LiL. DangC. Comprehensive analysis of alfa defensin expression and prognosis in human colorectal cancer.Front. Oncol.20231297465410.3389/fonc.2022.97465436703795
    [Google Scholar]
  16. 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]
  17. XuL. LiW. YangT. HuS. ZouQ. JiaoJ. JiangN. ZhangY. Immune-related RNA-binding protein-based signature with predictive and prognostic implications in patients with lung adenocarcinoma.Front. Mol. Biosci.2022980762210.3389/fmolb.2022.80762235647031
    [Google Scholar]
  18. 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]
  19. HuaH. PanS. DiaoH. CaoY. QianX. ZhangJ. Increased ACSL6 expression predicts a favorable prognosis in triple-negative breast cancer.Curr. Med. Chem.202432173513355010.2174/010929867327884623122210342038310395
    [Google Scholar]
  20. ChenL. GeM. MoS. ShiM. ZhangJ. LiuJ. Construction of a new ferroptosis-related prognosis model for survival prediction in colorectal cancer.Curr. Med. Chem.202432204132414638362684
    [Google Scholar]
  21. XuY. ShenY. BhandariA. HirachanS. WangO. XiaE. Serine protease 27, a prognostic biomarker in pan- cancer and associated with the aggressive progression of breast cancer.Curr. Med. Chem.202431152073208910.2174/092986733066623032416132937282654
    [Google Scholar]
  22. 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]
  23. CaiH. ChenS. WuZ. WangF. TangS. LiD. WangD. GuoW. Comprehensive analysis of ZNF692 as a potential biomarker associated with immune infiltration in a pan cancer analysis and validation in hepatocellular carcinoma.Aging20231522130411305810.18632/aging.20521837980166
    [Google Scholar]
  24. 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]
  25. 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]
  26. LiangL. XuH. DongQ. QiuL. LuL. YangQ. ZhaoW. LiY. WTAP is correlated with unfavorable prognosis, tumor cell proliferation, and immune infiltration in hepatocellular carcinoma.Front. Oncol.20221285200010.3389/fonc.2022.85200035480109
    [Google Scholar]
  27. 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]
  28. LuX. JingL. LiuS. WangH. ChenB. miR-149-3p is a potential prognosis biomarker and correlated with immune infiltrates in uterine corpus endometrial carcinoma.Int. J. Endocrinol.2022202211510.1155/2022/500612335719192
    [Google Scholar]
  29. 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]
  30. 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]
  31. YoshiharaK. ShahmoradgoliM. MartínezE. VegesnaR. KimH. GarciaT.W. TreviñoV. ShenH. LairdP.W. LevineD.A. CarterS.L. GetzG. HaleS.K. MillsG.B. VerhaakR.G.W. Inferring tumour purity and stromal and immune cell admixture from expression data.Nat. Commun.201341261210.1038/ncomms361224113773
    [Google Scholar]
  32. XuZ. PeiC. ChengH. SongK. YangJ. LiY. HeY. LiangW. LiuB. TanW. LiX. PanX. MengL. Comprehensive analysis of FOXM1 immune infiltrates, m6a, glycolysis and ceRNA network in human hepatocellular carcinoma.Front. Immunol.202314113852410.3389/fimmu.2023.113852437234166
    [Google Scholar]
  33. ChenB. DingX. WanA. QiX. LinX. WangH. MuW. WangG. ZhengJ. Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer.Sci. Rep.20231311624410.1038/s41598‑023‑42171‑537758722
    [Google Scholar]
  34. 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]
  35. 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]
  36. ShiB. ChuJ. HuangT. WangX. LiQ. GaoQ. XiaQ. LuoS. The scavenger receptor MARCO expressed by tumor-associated macrophages are highly associated with poor pancreatic cancer prognosis.Front. Oncol.20211177148810.3389/fonc.2021.77148834778091
    [Google Scholar]
  37. HandzlikG. SzymańskaE. PękalaE. KędzierskiL. StrzałkowskaD. DuławaJ. Low-sodium dietary approach in the management of resistant and refractory hypertension: Preliminary results.Pol. Arch. Intern. Med.20211311016098
    [Google Scholar]
  38. 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]
  39. ShiT. HuZ. TianL. YangY. Pan-cancer landscape of CENPO and its underlying mechanism in LUAD.Respir. Res.202324111310.1186/s12931‑023‑02408‑337061713
    [Google Scholar]
  40. JiangY. YouJ. WuC. KangY. ChenF. ChenL. WuW. High expression of DARS2 indicates poor prognosis in lung adenocarcinoma.J. Clin. Lab. Anal.20223610e2469110.1002/jcla.2469136085578
    [Google Scholar]
  41. LiuL. WangC. LiS. QuY. XueP. MaZ. ZhangX. BaiH. WangJ. ERO1L is a novel and potential biomarker in lung adenocarcinoma and shapes the immune- suppressive tumor microenvironment.Front. Immunol.20211267716910.3389/fimmu.2021.67716934354701
    [Google Scholar]
  42. 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]
  43. WeiD. SunD. SireraR. AfzalM.Z. LeongT.L. LiX. WangY. Overexpression of MRPL19 in predicting poor prognosis and promoting the development of lung adenocarcinoma.Transl. Lung Cancer Res.20231271517153810.21037/tlcr‑23‑30637577299
    [Google Scholar]
  44. ZisiA. BartekJ. LindströmM.S. Targeting ribosome biogenesis in cancer: Lessons learned and way forward.Cancers2022149212610.3390/cancers1409212635565259
    [Google Scholar]
  45. DyG.K. The role of focal adhesion kinase in lung cancer.Anticancer. Agents Med. Chem.201313458158310.2174/187152061131304000722934708
    [Google Scholar]
  46. HardenberghD. MolinaE. NaikR. GeethaD. ChaturvediS. TimlinH. Factors mediating cancer risk in systemic lupus erythematosus.Lupus202231111285129510.1177/0961203322112216336059254
    [Google Scholar]
  47. BaoY. WangL. ShiL. YunF. LiuX. ChenY. ChenC. RenY. JiaY. Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.Cell. Mol. Biol. Lett.20192413810.1186/s11658‑019‑0162‑031182966
    [Google Scholar]
  48. LiuJ. PengY. WeiW. Cell cycle on the crossroad of tumorigenesis and cancer therapy.Trends Cell Biol.2022321304410.1016/j.tcb.2021.07.00134304958
    [Google Scholar]
  49. ZhangJ. YangJ. DuvalC. EdinM.L. WilliamsA. LeiL. TuM. PourmandE. SongR. GravesJ.P. DeGraffL.M. WongJ.J.L. WangY. SunQ. SanidadK.Z. WongS. HanY. ZhangZ. LeeK.S.S. ParkY. XiaoH. LiuZ. DeckerE.A. CuiW. ZeldinD.C. ZhangG. CYP eicosanoid pathway mediates colon cancer-promoting effects of dietary linoleic acid.FASEB J.2023377e2300910.1096/fj.202300786R37273180
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673344310241216042749
Loading
/content/journals/cmc/10.2174/0109298673344310241216042749
Loading

Data & Media loading...

Supplements

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

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