ABSTRACT
Clear cell renal carcinoma (ccRCC) is one of the most common cancers worldwide. In this study, a new model of immune-related genes was developed to predict the overall survival and immunotherapy efficacy in patients with ccRCC. Immune-related genes were obtained from the ImmPort database. Clinical data and transcriptomics of ccRCC samples were downloaded from GSE29609 and The Cancer Genome Atlas. An immune-related gene-based prognostic model (IRGPM) was developed using the least absolute shrinkage and selection operator regression algorithm and multivariate Cox regression. The reliability of the developed models was evaluated by Kaplan-Meier survival curves and time-dependent receiver operating characteristic curves. Furthermore, we constructed a nomogram based on the IRGPM and multiple clinicopathological factors, along with a calibration curve to examine the predictive power of the nomogram. Overall, this study investigated the association of IRGPM with immunotherapeutic efficacy, immune checkpoints, and immune cell infiltration. Eleven IRGs based on 528 ccRCC samples significantly associated with survival were used to construct the IRGPM. Remarkably, the IRGPM, which consists of 11 hub genes (SAA1, IL4, PLAUR, PLXNB3, ANGPTL3, AMH, KLRC2, NR3C2, KL, CSF2, and SEMA3G), was found to predict the survival of ccRCC patients accurately. The calibration curve revealed that the nomogram developed with the IRGPM showed high predictive performance for the survival probability of ccRCC patients. Moreover, the IRGPM subgroups showed different levels of immune checkpoints and immune cell infiltration in patients with ccRCC. IRGPM might be a promising biomarker of immunotherapeutic responses in patients with ccRCC. Overall, the established IRGPM was valuable for predicting survival, reflecting the immunotherapy response and immune microenvironment in patients with ccRCC.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/therapy , Reproducibility of Results , Nomograms , Immunotherapy , Kidney Neoplasms/genetics , Kidney Neoplasms/therapy , Tumor Microenvironment/genetics , Angiopoietin-Like Protein 3 , NK Cell Lectin-Like Receptor Subfamily CABSTRACT
Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors in the world. NSCLC shows serious effect on prognosis for drug resistance, and it is necessary to study the molecular mechanism for drug resistance in NSCLC. Ubiquitin-proteasome system (UPS) can regulate some important cellular processes by degrading short-term protein, and the abnormal expression is closely related to the occurrence, development and prognosis of tumor. The F-box family protein is an important component of the ubiquitin proteasome, such as cycle regulation, transcriptional regulation, signal transduction, apoptosis and differentiation. F-box and WD-40 domain protein 7 (FBXW7) is just the classic protein components among F-box family protein. Studies have shown that FBXW7 is related to drug resistance in NSCLC. The main mechanism is that FBXW7 mutation leads to drug resistance by reducing ubiquitination and degradation of its downstream proteins, including Snail protein, myeloid cell leukemia sequence 1 (MCL-1), mammalian target of rapamycin (mTOR), and coiled-coil-domain containing 6 (CCDC6). Rapamycin, histone deacetylase inhibitor MS-275, and rabdosia are effective in drug-resistant NSCLC patients with FBXW7 mutation.
