A Novel Prognostic Signature for Survival Prediction and Immune Implication Based on SARS-CoV-2–Related Genes in Kidney Renal Clear Cell Carcinoma

Abstract

Kidney renal clear cell carcinoma (KIRC) is a common aggressive malignancy of the urinary system. COVID-19, a highly infectious and severe disease caused by SARS-CoV-2, has become a significant challenge for global public health. Cancer patients have been reported to be more vulnerable to SARS-CoV-2 infection and have a higher risk for serious complications than the general population. However, the correlation between KIRC and COVID-19 remains incompletely elucidated. In this study, we comprehensively investigated the expression and prognostic significance of 333 SARS-CoV-2 infection–related genes in KIRC using the TCGA dataset and identified 31 SARS-CoV-2–related differently expressed genes between KIRC and normal renal tissues. Based on these genes, we constructed and validated a 5-gene prognostic signature (including ACADM, CENPF, KDELC1, PLOD2, and TRMT1) to distinguish low- and high-risk KIRC patients of poor survival in TCGA and E-MTAB-1980 cohorts. Gene set enrichment analysis (GSEA) showed that some inflammatory/immune-related pathways were significantly enriched in the high-risk group. The ESTIMATE analysis indicated that patients in the high-risk group had higher stromal and immune cell scores, therefore lower tumor purity. Moreover, they presented higher proportions of macrophages M0, regulatory T cells (Tregs), and T follicular helper cells and higher expression of immune checkpoints CTLA-4, LAG-3, TIGIT, and PDCD1 than low-risk patients. Besides, we also developed a nomogram to expand clinical applicability, which exhibits excellent predictive accuracy for survival. In conclusion, we identified a novel prognostic signature and nomogram based on SARS-CoV-2–related genes as reliable prognostic predictors for KIRC patients and provided potential therapeutic targets for KIRC and COVID-19.

Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

“…With a view to the significance of the immune system in antiviral and antitumor responses, we calculated the proportion of different types of tumor-infiltrating immune cells in BRCA using CIBERSORT and used ESTIMATE to explore IS, SS, and tumor purity. Higher SSs and ISs were observed in high-risk patients, leading to an unfavorable prognosis, which was consistent with a line of evidence from previous research ( 46 , 47 ).…”

Construction of an endoplasmic reticulum stress-related gene model for predicting prognosis and immune features in kidney renal clear cell carcinoma

“…Although there have been advances in multiple therapeutic methods, including surgery, chemotherapy, and immunotherapy, the prognosis of KIRC patients remains a major clinical challenge because of the high incidence of recurrence and metastasis. As reported, the recurrence rate of KIRC after curative nephrectomy is approximately 20-30% within 5 years (Huang et al, 2021). More importantly, studies have shown that the 5-year overall survival rate is less than 10% in metastatic KIRC patients (Xing et al, 2020;Lamprou et al, 2021).…”

Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infiltration

“…ACADM is believed to be one of the important enzymes participated in amino acid metabolism of colon cancer tumor-associated macrophages (TAMs), and the elevated level of ACADM is linked with a more favorable outcome for colon cancer individuals [ 42 ]. In a study of prognostic features of renal cancer according to SARS-CoV-2 related genes, a model constructed with ACADM as one of the hub genes was linked with infiltration of multiple cells of immunity [ 43 ]. According to the findings of our study, ACADM was associated with the infiltration of a number of different immune cells, including Treg cells.…”