TY - JOUR TI - Prognostic and therapeutic implications of extracellular matrix associated gene signature in renal clear cell carcinoma AU - Ahluwalia, Pankaj AU - Ahluwalia, Meenakshi AU - Mondal, Ashis K. AU - Sahajpal, Nikhil AU - Kota, Vamsi AU - Rojiani, Mumtaz V. AU - Rojiani, Amyn M. AU - Kolhe, Ravindra T2 - Scientific Reports AB - Complex interactions in tumor microenvironment between ECM (extra-cellular matrix) and cancer cell plays a central role in the generation of tumor supportive microenvironment. In this study, the expression of ECM-related genes was explored for prognostic and immunological implication in clear cell renal clear cell carcinoma (ccRCC). Out of 964 ECM genes, higher expression (z-score > 2) of 35 genes showed significant association with overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS). On comparison to normal tissue, 12 genes (NUDT1, SIGLEC1, LRP1, LOXL2, SERPINE1, PLOD3, ZP3, RARRES2, TGM2, COL3A1, ANXA4, and POSTN) showed elevated expression in kidney tumor (n = 523) compared to normal (n = 100). Further, Cox proportional hazard model was utilized to develop 12 genes ECM signature that showed significant association with overall survival in TCGA dataset (HR = 2.45; 95% CI [1.78–3.38]; p < 0.01). This gene signature was further validated in 3 independent datasets from GEO database. Kaplan–Meier log-rank test significantly associated patients with elevated expression of this gene signature with a higher risk of mortality. Further, differential gene expression analysis using DESeq2 and principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters between ECM-rich high-risk and ECM-poor low-risk patients. Geneset enrichment analysis (GSEA) identified significant perturbations in homeostatic kidney functions in the high-risk group. Further, higher infiltration of immunosuppressive T-reg and M2 macrophages was observed in high-risk group patients. The present study has identified a prognostic signature with associated tumor-promoting immune niche with clinical utility in ccRCC. Further exploration of ECM dynamics and validation of this gene signature can assist in design and application of novel therapeutic approaches. DA - 2021/04/07/ PY - 2021 DO - 10.1038/s41598-021-86888-7 DP - www.nature.com VL - 11 IS - 1 SP - 7561 LA - en SN - 2045-2322 UR - https://www.nature.com/articles/s41598-021-86888-7 Y2 - 2021/04/08/16:54:55 ER -