Yu C, You M, Zhang P, et al. - Researchers investigated whether extracellular matrix (ECM) regulators have an important role in pan-cancer attribution by inducing a generic impact via its regulation of the dynamics of ECM alteration. They studied data from The Cancer Genome Atlas (TCGA) employing gene set enrichment analysis and univariate Cox regression analysis, and identified significant enrichment of ECM regulator genes as well as their contribution to mortality in several cancer types. They discovered a five-gene signature comprising the predominant ECM regulators ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3. Experts identified that this five-gene signature was pro-mortality in 18 types of malignancy in TCGA, as well as validated 11 other malignancy types in TCGA and seven types in the TARGET (Tumor Alterations Relevant for Genomics-driven Therapy) and CoMMpass (Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile) databases employing overall survival analysis. Overall, it was inferred that the ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3 signature not only demonstrated a close relationship with a pan-cancer impact on prognosis but was also identified to be associated with ECM proteins in the tumor microenvironment which corresponding with immunologically “cold” cancer types.