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CGB5, INHBA and TRAJ19 Hold Prognostic Potential as Immune Genes for Patients with Gastric Cancer

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Abstract

Background

Gastric cancer (GC) seriously threatens people’s health and life quality worldwide.

Aim

The current study sought to explore prognostic immune genes and their regulatory network in GC.

Methods

First, expression data in GC and normal samples were analyzed based on bioinformatics analysis. Immune-related genes were identified and confirmed with univariate/multivariate Cox analysis and receiver-operating characteristic curve. The upstream transcription factors of immune genes were subsequently predicted, and their regulatory network was constructed. GC and adjacent normal tissues were obtained from 76 patients with GC to determine the expression patterns of immune genes and their correlation with overall prognosis. CD8+ T-cell infiltration of patients with high or low risk was detected by means of immunohistochemistry.

Results

Bioinformatics analysis highlighted 3689 differentially expressed genes in GC, including 87 immune genes, 8 of which were significantly associated with patient survival. CGB5 and INHBA were high-risk genes, while TRAJ19 was identified as a low-risk gene, all of which were found to be regulated by 11 different transcription factors. Furthermore, CGB5 and INHBA exhibited negative correlation with the prognosis of GC patients; however, TRAJ19 was positively correlated with GC patient prognosis. The incidence of lymph node metastasis was higher, the pathological stage was advanced and the infiltrated CD8+ T cells were fewer in the high-risk GC group.

Conclusions

Overall, our findings identified the key roles of CGB5, INHBA and TRAJ19 in prognosis GC patients, serving as an important gene set for prognostic prediction.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

GC:

Gastric cancer

GTEx:

Genotype-Tissue Expressionx

DEGs:

Differentially expressed genes

FACS:

Fluorescence activated cell sorting

RT-qPCR:

Reverse transcription quantitative polymerase chain reaction

References

  1. Eusebi LH, Telese A, Marasco G et al. Gastric cancer prevention strategies: a global perspective. J Gastroenterol Hepatol. 2020;35:1495–1502.

    Article  PubMed  Google Scholar 

  2. Machlowska J, Baj J, Sitarz M et al. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci 2020;21:4012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zhang Y, Yu J. The role of MRI in the diagnosis and treatment of gastric cancer. Diagn Interv Radiol 2020;26:176–182.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sitarz R, Skierucha M, Mielko J et al. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018;10:239–248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Refolo MG, Lotesoriere C, Messa C et al. Integrated immune gene expression signature and molecular classification in gastric cancer: new insights. J Leukoc Biol. 2020;108:633–646.

    Article  CAS  PubMed  Google Scholar 

  6. Foukakis T, Lovrot J, Matikas A et al. Immune gene expression and response to chemotherapy in advanced breast cancer. Br J Cancer. 2018;118:480–488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tsakonas G, Lewensohn R, Botling J et al. An immune gene expression signature distinguishes central nervous system metastases from primary tumours in non-small-cell lung cancer. Eur J Cancer. 2020;132:24–34.

    Article  CAS  PubMed  Google Scholar 

  8. Huang R, Chen Z, Li W et al. Immune systemassociated genes increase malignant progression and can be used to predict clinical outcome in patients with hepatocellular carcinoma. Int J Oncol. 2020;56:1199–1211.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Li L, Wang XL, Lei Q et al. Comprehensive immunogenomic landscape analysis of prognosis-related genes in head and neck cancer. Sci Rep. 2020;10:6395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nakamura K, Hatakeyama K, Furukawa K et al. Prediction of S-1 adjuvant chemotherapy benefit in Stage II/III gastric cancer treatment based on comprehensive gene expression analysis. Gastric Cancer. 2020;23:648–658.

    Article  CAS  PubMed  Google Scholar 

  11. Newman AM, Liu CL, Green MR et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ali HR, Chlon L, Pharoah PD et al. Patterns of immune infiltration in breast cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 2016;13:e1002194.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schleif RF. Modulation of DNA binding by gene-specific transcription factors. Biochemistry. 2013;52:6755–6765.

    Article  CAS  PubMed  Google Scholar 

  14. Mierke CT. The matrix environmental and cell mechanical properties regulate cell migration and contribute to the invasive phenotype of cancer cells. Rep Prog Phys. 2019;82:064602.

    Article  CAS  PubMed  Google Scholar 

  15. Kang BW, Kim JG, Lee IH et al. Clinical significance of tumor-infiltrating lymphocytes for gastric cancer in the era of immunology. World J Gastrointest Oncol. 2017;9:293–299.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Farhood B, Najafi M, Mortezaee K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol. 2019;234:8509–8521.

    Article  CAS  PubMed  Google Scholar 

  17. Nie K, Shi L, Wen Y et al. Identification of hub genes correlated with the pathogenesis and prognosis of gastric cancer via bioinformatics methods. Minerva Med. 2019;111:213–225.

    PubMed  Google Scholar 

  18. Yang Y, Shi Y, Hou Y et al. CGB5 expression is independently associated with poor overall survival and recurrence-free survival in patients with advanced gastric cancer. Cancer Med. 2018;7:716–725.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chen Y, Kibriya MG, Jasmine F et al. Do placental genes affect maternal breast cancer? Association between offspring’s CGB5 and CSH1 gene variants and maternal breast cancer risk. Cancer Res. 2008;68:9729–9734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li X, Yu W, Liang C et al. INHBA is a prognostic predictor for patients with colon adenocarcinoma. BMC Cancer. 2020;20:305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Liu X, Liu X, Qiao T et al. Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis. Oncol Lett. 2020;19:1881–1889.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang W, He Y, Zhao Q et al. Identification of potential key genes in gastric cancer using bioinformatics analysis. Biomed Rep. 2020;12:178–192.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Biskup K, Blanchard V, Castillo-Binder P et al. N- and O-glycosylation patterns and functional testing of CGB7 versus CGB3/5/8 variants of the human chorionic gonadotropin (hCG) beta subunit. Glycoconj J. 2020;37:599–610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sun YL, Zhang Y, Guo YC et al. A prognostic model based on the immune-related genes in colon adenocarcinoma. Int J Med Sci. 2020;17:1879–1896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wan H, Liu Z, Tan X et al. Application of immune cell infiltration in the diagnosis and prognosis of non-small cell lung cancer. Sheng Wu Gong Cheng Xue Bao 2020;36:740–749.

    CAS  PubMed  Google Scholar 

  26. Wu M, Ding J, Song J et al. Genomic analysis and clinical implications of immune cell infiltration in gastric cancer. Biosci Rep. 2020;40:BSR20193308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. De Rossi A, Huaman SD, Leon J et al. Fibroblast growth factor receptor 2 expression in apical periodontitis in mice. Int Endod J. 2020;53:1111–1119.

    Article  PubMed  Google Scholar 

  28. Ramakrishna B, Yewale R, Vijayakumar K et al. Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor. J Pathol Transl Med. 2020;54:258.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lou JS, Wang JF, Fei MM et al. Targeting LAG-3 reverses T lymphocytes dysfunction and improves survival in murine polymicrobial sepsis. J Infect Dis. 2020;222:1051–1061.

    Article  CAS  PubMed  Google Scholar 

  30. Yuan X, Tang Y, Zhao Z et al. Identification and verification of EOMEs regulated network in Alopecia areata. Int Immunopharmacol. 2020;84:106544.

    Article  CAS  PubMed  Google Scholar 

  31. Taveirne S, Wahlen S, Van Loocke W et al. The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation. Blood 2020;136:288–298.

    PubMed  Google Scholar 

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Acknowledgments

We acknowledge and appreciate our colleagues for their valuable contributions to this work.

Funding

Project ZR2019PH102 supported by Shandong Provincial Natural Science Foundation.

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Authors and Affiliations

  1. Department of Gastroenterology, The Second People’s Hospital of Liaocheng, The Second Hospital of Liaocheng Affiliated to Shandong First Medical University, No. 306, Jiankang Road, Liaocheng, 252600, Shandong Province, People’s Republic of China

    Bei Ji, Lili Qiao & Wei Zhai

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  1. Bei Ji
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  2. Lili Qiao
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  3. Wei Zhai
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Contributions

BJ and WZ designed the project and prepared the main manuscript. LLQ prepared the manuscript and figures. All authors agreed to the publication. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Wei Zhai.

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The authors declare no conflict of interests.

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Cite this article

Ji, B., Qiao, L. & Zhai, W. CGB5, INHBA and TRAJ19 Hold Prognostic Potential as Immune Genes for Patients with Gastric Cancer. Dig Dis Sci 68, 791–802 (2023). https://doi.org/10.1007/s10620-022-07513-9

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  • DOI: https://doi.org/10.1007/s10620-022-07513-9

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