CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray analysis

Abstract

BackgroundHepatocellular carcinoma (HCC) is a tumor with a high recurrence rate, poor prognosis, and rapid progression. Therefore, it is necessary to find a novel biomarker for HCC. Coiled-coil domain containing 25 (CCDC25) has been identified as a target molecule that mediates liver metastasis in colon cancer. However, the molecular mechanisms of CCDC25 in HCC are unknown. This study aimed to explore the role of CCDC25 in HCC.MethodsThe expression of CCDC25 in HCC was identified through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic curve (ROC) curves were drawn to evaluate the diagnostic value of CCDC25 for HCC. The effect of CCDC25 on the prognosis of HCC was analyzed by using the Kaplan–Meier plotter. Co-expressed genes and Gene Set Enrichment Analysis (GSEA) were used to explore the related functions and regulatory signaling pathways of CCDC25. Moreover, we employed the Tumor Immune Estimation Resource (TIMER) database and CIBERSORT algorithm to investigate the relationship between CCDC25 and the tumor immune microenvironment (TME) in HCC. Meanwhile, the effect of CCDC25 on the sensitivity of HCC patients to chemotherapy drugs was evaluated. Finally, we explored the prognostic methylation sites of CCDC25 using the MethSurv database.ResultsCCDC25 expression was low in HCC. Low CCDC25 expression was significantly associated with poor overall survival of HCC and may be comparable to the ability of AFP to diagnose HCC. Dysregulation of glucose metabolism, fatty acid metabolism, amino acid metabolism, ubiquitination modification, and apoptosis inhibition caused by CCDC25 downregulation may be the causes and results of HCC. In addition, CCDC25 was positively correlated with the infiltration level of various adaptive antitumor immune cells. The levels of immune cell infiltration and immune checkpoint expression were lower in the samples with high CCDC25 expression. What is more, we found that downregulated CCDC25 may increase the sensitivity or resistance of HCC patients to multiple drugs, including sorafenib. We also identified a methylation site for CCDC25, which may be responsible for poor prognosis and low CCDC25 expression in HCC patients. Finally, CCDC25 may be associated with HCC ferroptosis.ConclusionsCCDC25 may be a potential diagnostic and prognostic marker for HCC and is associated with immune infiltration and ferroptosis.

Coiled‐coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK‐NF‐κB signaling pathway

“…A study in nature found that CCDC25 is a plasma membrane‐bound extracellular DNA sensor, which can be used as a target molecule for neutrophil extracellular trap (NET)‐mediated metastasis to further inhibit cancer cell metastasis 9 . Furthermore, Deng et al 10 . and Saeraneere et al 11 .…”

“…Recent studies have revealed that CCDC25 is a plasma membrane‐bound extracellular DNA sensor that has been described as an NET‐mediated cancer spread target 9 . Furthermore, Deng et al 10 . and Saeraneere et al 11 .…”

“…8 Recent studies have revealed that CCDC25 is a plasma membrane-bound extracellular DNA sensor that has been described as an NET-mediated cancer spread target. 9 Furthermore, Deng et al 10 and Saeraneere et al 11 reported that CCDC25 is a potential diagnostic and prognostic marker of cholangiocarcinoma and hepatocellular carcinoma. Nevertheless, the role of CCDC25 in ccRCC is currently unclear.…”

Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy

“…However, a contradiction here is that HCCs with low expression of CCDC25 are more sensitive to sorafenib, lapatinib, and gefitinib. The specific mechanism here may involve the process of ferroptosis[ 58 ]. Sorafenib also influences lipid metabolism; for example, it can increase the level of erythropoietic acid (EETs) in the blood, and these EETs, in turn, affect the efficacy of sorafenib.…”

“…A study showed that CCDC25 is positively correlated with the infiltration of CD8 + T cells, macrophages, and dendritic cells, while negatively correlated with regulatory T cells (Treg) infiltration and the expression level of immune checkpoints such as PDCD1, CTLA4, and TIGIT. CCDC25 also blocked the immune escape of tumors by upregulating tumor killer cells, downregulating immunosuppressive cells, and inhibiting immune checkpoints[ 58 ].…”