CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types

Abstract

Background. Cancer is a major threat to human health worldwide. Although recent innovations and advances in early detection and effective therapies such as targeted drugs and immune checkpoint inhibitors have saved more lives of cancer patients and improved their quality of life, our knowledge about cancer remains largely unknown. CCNA2 belongs to the cell cyclin family and has been demonstrated to be a tumorigenic gene in multiple solid tumor types. The aim of the present study was to make a comprehensive analysis on the role of CCNA2 at a pancancer level. Methods. Multidatabases were collected to evaluate the different expression, prognostic value, DNA methylation, tumor mutation burden, microsatellite instability, mismatch repair, tumor immune microenvironment, and drug sensitivity of CCNA2 across pancancer. IHC was utilized to validate the expression and prognostic value of CCNA2 in ccRCC patients from SMMU cohort. Results. CCNA2 was differentially expressed in most cancer types vs. normal tissues. CCNA2 may significantly influence the prognosis of multiple cancer types, especially clear cell renal cell carcinoma (ccRCC). CCNA2 was also frequently mutated in most cancer types. Notably, CCNA2 was significantly correlated with immune cell infiltration and immune checkpoint inhibitory genes. In addition, CCNA2 was also strongly related to drug resistance. Conclusion. CCNA2 may prove to be a new biomarker for prognostic prediction, tumor immunity assessment, and drug susceptibility evaluation in pancancer level, especially in ccRCC.

A new thinking: deciphering the aberrance and clinical implication of copper-death signatures in clear cell renal cell carcinoma

“…Even the emergence of checkpoint inhibition has alleviated this condition, and the combination of immune blockade and targeted therapy has been the standard of management for advanced ccRCC patients [39]. The major challenges facing clinical practitioners were that only a substantial proportion of patients could benefit from checkpoint blockade and the extremely horrible adverse reactions of such therapies [40,41]. Thus, it is urgent to identify new therapeutic targets or adjuvants to aid immune therapy for ccRCC.…”

Gene dysregulation in acute HIV-1 infection – early transcriptomic analysis reveals the crucial biological functions affected

“…With the exception of SKA3, these eight genes have established protein-protein interactions ( Figure 4 ), with protein activities implying that viral load is associated with numerous core functions across the cell cycle process. Specifically, these core functions include initiation of DNA replication [via MCM4-led increased DNA helicase unwinding ( Bochman and Schwacha, 2009 ), and loading of DNA polymerase alpha onto chromatin through CDC45 and possibly GINS complex activity ( Bochman and Schwacha, 2009 )]; and positive regulation of progression through G1, S and G2 phases through CCNA2 ( Jiang et al., 2022 ). Notably, CCNA2 has been associated with aberrant cell cycle progression in several types of cancer, and has been posited as a potential therapeutic target that could be inhibited to repress cell proliferation ( Ma, 2019 ; Yang et al., 2020 ).…”

Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma

“…In this study, we revealed some key proteins that may be closely related to CENPM by correlation analysis and PPI network construction, including: CCNA2, CCNB2, CDC20, AURKB, ASPM, BUB1 and TOP2A. Interestingly, these molecules have been shown to be associated with the malignant phenotype and poor prognosis of ccRCC in past studies [27][28][29][30]. Not only does this evidence provide a potential regulatory network, it also seems to indirectly validate the malignant function of CENPM in ccRCC.…”