Metastatic Immune-Related Genes for Affecting Prognosis and Immune Response in Renal Clear Cell Carcinoma

Abstract

Background: In renal clear cell carcinoma, a common cancer of the urinary system, 25–30% patients are metastatic at initial diagnosis and 20–30% patients have a tendency of recurrence and metastasis after local surgery. With the rapid development of tumor immunology, immune agents have brought new directions to tumor therapy. However, no relevant studies have explored the role of immune-related genes in kidney cancer metastasis.Methods: Co-expressed metastatic immune-related differentially expressed genes (mIR-DEGs) were screened by GSE12606, GSE47352, and immunorelated genes. Then, differential expression analysis, prognostic analysis, and univariate and multivariate Cox regression analysis in KIRC were performed to determine independent prognostic factors associated, and the risk prognostic model was established. The correlation of hub mIR-DEGs with clinicopathological factors, immune invasion, and immune checkpoints was analyzed, and the expression of hub mIR-DEGs and their effect on tumor were re-evaluated by OCLR scores in KIRC.Results: By comprehensive bioassay, we found that FGF17, PRKCG, SSTR1, and SCTR were mIR-DEGs with independent prognostic values, which were significantly associated with clinicopathological factors and immune checkpoint–related genes. The risk prognostics model built on this basis had good predictive potential. In addition, targeted small molecule drugs, including calmidazolium and sulfasalazine, were predicted for mIR-DEGs. Further experimental results were consistent with the bioinformatics analysis.Conclusion: This study preliminarily confirmed that FGF17, PRKCG, SSTR1, and SCTR were targeted genes affecting renal cancer metastasis and related immune responses and can be used as potential therapeutic targets and prognostic biomarkers for renal cancer. Preliminary validation found that PRKCG and SSTR1 were consistent with predictions.

Immunological role and prognostic value of somatostatin receptor family members in colon adenocarcinoma

“…High SSTR1 expression can silence and inhibit the proliferative rate of CRC stem cells by reducing the proliferation of acetaldehyde dehydrogenase-positive cells (Modarai et al, 2016). One preliminary study (Sun et al, 2021) confirmed that SSTR1 is a target gene affecting renal cell carcinoma (RCC) metastasis and the associated immune response and could be a prognostic biological marker of and viable therapeutic target for RCC. Another study (Zhou et al, 2009) found that the antiproliferative effects of SSTR2 were both cytostatic (growth suppression) and cytotoxic (apoptosis) by affecting the cellular apoptotic level, MAPK, and angiogenic signaling molecules in SSTR2-positive and -negative cancers.…”

ASNS can predict the poor prognosis of clear cell renal cell carcinoma

“…The studies involving human participants were reviewed and approved by Ethics Committee and Institutional Review Board for Clinical Research of Zhongda Hospital (ZDKYSB077) ( 43 , 44 , 45 , 46 ). This study is a retrospective study that only collected clinical data from patients, and the ethical committee approved the exemption of informed consent.…”

Immune cell related signature predicts prognosis in esophageal squamous cell carcinoma based on single-cell and bulk-RNA sequencing

“…Against this backdrop, immunotherapy has recently become an effective and safe method of treating tumors ( 9 , 10 ). Immunotherapy reduces tumor metastasis and recurrence by stimulating specific immune responses to suppress and kill tumor cells ( 11 ). Research has demonstrated favorable therapeutic effects of monoclonal antibodies targeting programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) in treating ESCC ( 12 , 13 ).…”