Prognostic model of kidney renal clear cell carcinoma using aging-related long noncoding RNA signatures identifies THBS1-IT1 as a potential prognostic biomarker for multiple cancers

Abstract

Aging is responsible for the main intrinsic triggers of cancers; however, the studies of aging risk factors in cancer animal models and cancer patients are rare and insufficient to be represented in cancer clinical trials. For a better understanding of the complex regulatory networks of aging and cancers, 8 candidate aging related long noncoding RNAs (CarLncs) identified from the healthy aging models, centenarians and their offsprings, were selected and their association with kidney renal clear cell carcinoma (KIRC) was explored by series of cutting edge analyses such as support vector machine (SVM) and random forest (RF) algorithms. Using data downloaded from TCGA and GTEx databases, a regulatory network of CarLncs-miRNA-mRNA was constructed and five genes within the network were screened out as aging related feature genes for developing KIRC prognostic models. After a strict filtering pipeline for modeling, a formula using the transcript per million (TPM) values of feature genes “LncAging_score = 0.008* MMP11 + 0.066* THBS1-IT1 + (-0.014)* DYNLL2 + (-0.030)* RMND5A+ 0.008* PEG10” was developed. ROC analysis and nomogram suggest our model achieves a great performance in KIRC prognosis. Among the 8 CarLncs, we found that THBS1-IT1 was significantly dysregulated in 12 cancer types. A comprehensive pan-cancer analysis demonstrated that THBS1-IT1 is a potential prognostic biomarker in not only KIRC but also multiple cancers, such as LUSC, BLCA, GBM, LGG, MESO, PAAD, STAD and THCA, it was correlated with tumor microenvironment (TME) and tumor immune cell infiltration (TICI) and its high expression was related with poor survival.