Immune-related genes LAMA2 and IL1R1 correlate with tumor sites and predict poor survival in pancreatic adenocarcinoma
Abstract
Aims: The aim of this study was to identify the immune- and locus-associated genes in pancreatic ductal adenocarcinoma and evaluate their value in prognosis. Methods: The pancreatic ductal adenocarcinoma stromal and immune scores were calculated with the estimation of stromal and immune cells in malignant tumor tissues using expression data algorithm. The authors screened the differentially expressed genes to generate immune- and stromal-related differentially expressed genes. Next, the authors conducted weighted correlation network analysis to find the gene sets related to tumor sites. Results:IL1R1 and LAMA2 were identified as the site- and immune-related genes in pancreatic ductal adenocarcinoma, and their high expression in pancreatic head cancer exhibited high immune scores and predicted unfavorable prognosis. Conclusion: The authors identified IL1R1 and LAMA2 as immune- and locus-associated genes, and their high expression predicted a poor prognosis.
Lay abstract
The prognosis of pancreatic cancer is poor, and pancreatic head carcinoma is different from pancreatic body/tail carcinoma in many respects. In recent years, the role of the immune microenvironment in tumors has been increasingly revealed. The authors wanted to find ways to improve the diagnosis and treatment of patients with pancreatic cancer by analyzing the key genes associated with different immune scores and pancreatic cancer sites. In the authors' study, IL1R1 and LAMA2 were identified as immune- and locus-associated genes, and their high expression predicted a poor prognosis, especially in pancreatic body/tail cancer. Early identification of high IL1R1 expression in pancreatic body/tail carcinoma may improve tumor prognosis.
Papers of special note have been highlighted as: •• of considerable interest
References
- 1. . Epidemiology of pancreatic cancer. World J. Gastroenterol. 22(44), 9694–9705 (2016).
- 2. . Vagaries of clinical presentation of pancreatic and biliary tract cancer. Ann. Oncol. 10(Suppl. 4), 82–84 (1999).
- 3. Comparative bioinformatical analysis of pancreatic head cancer and pancreatic body/tail cancer. Med. Oncol. 37(5), 46 (2020). •• Analyzes differentially expressed genes (DEGs) and mutation signatures of pancreatic head cancer and pancreatic body/tail cancer.
- 4. The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma. Oncotarget 8(9), 15159–15167 (2017).
- 5. . Head and body/tail pancreatic carcinomas are not the same tumors. Cancers (Basel) 11(4), 497 (2019). •• Provides support for the authors' study.
- 6. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531(7592), 47–52 (2016). •• Provides support for the authors' study.
- 7. Tumor microenvironment in head and neck squamous cell carcinoma. Semin. Oncol. 41(2), 217–234 (2014). •• Explains the importance of the tumor microenvironment.
- 8. The tumor microenvironment strongly impacts master transcriptional regulators and gene expression class of glioblastoma. Am. J. Pathol. 180(5), 2108–2119 (2012). •• Explains the importance of the tumor microenvironment.
- 9. The immune score as a new possible approach for the classification of cancer. J. Transl. Med. 10, 1 (2012). •• Explains the importance of the tumor microenvironment.
- 10. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 4, 2612 (2013).
- 11. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol. 17(1), 231 (2016).
- 12. . The expression pattern of matrix-producing tumor stroma is of prognostic importance in breast cancer. BMC Cancer 16(1), 841 (2016).
- 13. . Hallmarks of cancer: the next generation. Cell 144(5), 646–674 (2011). •• Provides support for the authors' study.
- 14. . Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21(3), 309–322 (2012).
- 15. Tumor microenvironment participates in metastasis of pancreatic cancer. Mol. Cancer 17(1), 108 (2018).
- 16. Stromal microenvironment shapes the intratumoral architecture of pancreatic cancer. Cell 178(1), 160–175.e127 (2019). •• Provides support for the authors' study.
- 17. . IL-1 receptor 2 (IL-1R2) and its role in immune regulation. Brain Behav. Immun. 32, 1–8 (2013).
- 18. . ClustVis: a web tool for visualizing clustering of multivariate data using principal component analysis and heatmap. Nucleic Acids Res. 43(W1), W566–W570 (2015).
- 19. Venny 2.1.0. (2014). http://bioinfogp.cnb.csic.es/tools/venny/index.html
- 20. . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4(1), 44–57 (2009).
- 21. . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37(1), 1–13 (2009).
- 22. . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9, 559 (2008).
- 23. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 77(21), e108–e110 (2017).
- 24. SangerBox. http://www.sangerbox.com/tool
- 25. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 214(3), 579–596 (2017).
- 26. Tumor-neuroglia interaction promotes pancreatic cancer metastasis. Theranostics 10(11), 5029–5047 (2020).
- 27. Dynamic proteomic analysis of pancreatic mesenchyme reveals novel factors that enhance human embryonic stem cell to pancreatic cell differentiation. Stem Cells Int. 2016, 6183562 (2016).
- 28. Expression and methylation status of LAMA2 are associated with the invasiveness of nonfunctioning PitNET. Ther. Adv. Endocrinol. Metab. 10, 2042018818821296 (2019).
- 29. Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes. Ann. Oncol. 28(3), 604–610 (2017).