Comprehensive characterization of immune- and inflammation-associated biomarkers based on multi-omics integration in kidney renal clear cell carcinoma
Tóm tắt
Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer in adults, and it is responsible for approximately 90–95% of cases. Although extensive evidence has suggested that many immune- and inflammation-related genes could serve as effective biomarkers in KIRC, the potential associations among immune-, inflammation- and KIRC-related genes has not been sufficiently understood. Here, we integrated multiple levels of data to construct an immune-, inflammation- or KIRC-directed neighbour network (IIKDN network) and a KIRC-related gene-directed network (KIRCD network). Our analysis suggested that immune- and inflammation-related genes in the network have special topological characteristics and expression patterns related to KIRC. We further identified five core clusters that showed a tighter network structure and stronger correlation of expression from the KIRCD network. Specifically, multiple-level molecular characteristics were systematically portrayed, including somatic mutation, copy-number variant and DNA methylation for the genes in five core clusters. We discovered that the genes showed strong correlation with respect to the expression and methylation levels in these five core clusters. These five core clusters could become special prognostic biomarkers for KIRC, and functional analysis showed that they were associated with activation of the immune and inflammation systems and cancer progression. Our findings highlighted the novel role of the immune and inflammation genes in KIRC.
Tài liệu tham khảo
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.
Sinha R, Winer AG, Chevinsky M, Jakubowski C, Chen YB, Dong Y, Tickoo SK, Reuter VE, Russo P, Coleman JA, et al. Analysis of renal cancer cell lines from two major resources enables genomics-guided cell line selection. Nat Commun. 2017;8:15165.
Scelo G, Purdue MP, Brown KM, Johansson M, Wang Z, Eckel-Passow JE, Ye Y, Hofmann JN, Choi J, Foll M, et al. Genome-wide association study identifies multiple risk loci for renal cell carcinoma. Nat Commun. 2017;8:15724.
Atkins MB, Tannir NM. Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma. Cancer Treat Rev. 2018;70:127–37.
Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and cancer mechanisms: tumor microenvironment and inflammation. J Clin Oncol. 2016;34:4270–6.
Hui L, Chen Y. Tumor microenvironment: sanctuary of the devil. Cancer Lett. 2015;368:7–13.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.
Taniguchi K, Karin M. NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18:309–24.
Chevrier S, Levine JH, Zanotelli VRT, Silina K, Schulz D, Bacac M, Ries CH, Ailles L, Jewett MAS, Moch H, et al. An immune atlas of clear cell renal cell carcinoma. Cell. 2017;169(736–749):e718.
Chang Y, An H, Xu L, Zhu Y, Yang Y, Lin Z, Xu J. Systemic inflammation score predicts postoperative prognosis of patients with clear-cell renal cell carcinoma. Br J Cancer. 2015;113:626–33.
Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13:759–71.
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499:43–9.
Sato Y, Yoshizato T, Shiraishi Y, Maekawa S, Okuno Y, Kamura T, Shimamura T, Sato-Otsubo A, Nagae G, Suzuki H, et al. Integrated molecular analysis of clear-cell renal cell carcinoma. Nat Genet. 2013;45:860–7.
Carbon S, Ireland A, Mungall CJ, Shu S, Marshall B, Lewis S. AmiGO: online access to ontology and annotation data. Bioinformatics. 2009;25:288–9.
Pinero J, Bravo A, Queralt-Rosinach N, Gutierrez-Sacristan A, Deu-Pons J, Centeno E, Garcia-Garcia J, Sanz F, Furlong LI. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 2017;45:D833–9.
Peri S, Navarro JD, Kristiansen TZ, Amanchy R, Surendranath V, Muthusamy B, Gandhi TK, Chandrika KN, Deshpande N, Suresh S, et al. Human protein reference database as a discovery resource for proteomics. Nucleic Acids Res. 2004;32:D497–501.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13:2498–504.
Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, Koplev S, Jenkins SL, Jagodnik KM, Lachmann A, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:W90–7.
Zhou H, Watts JD, Aebersold R. A systematic approach to the analysis of protein phosphorylation. Nat Biotechnol. 2001;19:375–8.
O’Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311–28.
Waldmann TA, Chen J. Disorders of the JAK/STAT pathway in T cell lymphoma pathogenesis: implications for immunotherapy. Annu Rev Immunol. 2017;35:533–50.
O’Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36:542–50.
Pantuck AJ, Klatte T, Seligson D, Atkins M, Belldegrun A. Carbonic anhydrase IX as a predictive biomarker for clear cell renal cell carcinoma. J Clin Oncol. 2008;26:3105–7 (author reply 3107-3109).
Ricketts CJ, Crooks DR, Linehan WM. Targeting HIF2alpha in clear-cell renal cell carcinoma. Cancer Cell. 2016;30:515–7.
Schlosberg CE, VanderKraats ND, Edwards JR. Modeling complex patterns of differential DNA methylation that associate with gene expression changes. Nucleic Acids Res. 2017;45:5100–11.
Sun W, Bunn P, Jin C, Little P, Zhabotynsky V, Perou CM, Hayes DN, Chen M, Lin DY. The association between copy number aberration, DNA methylation and gene expression in tumor samples. Nucleic Acids Res. 2018;46:3009–18.
Rogovskii VS. The linkage between inflammation and immune tolerance: interfering with inflammation in cancer. Curr Cancer Drug Targets. 2017;17:325–32.