RBM12 drives PD-L1-mediated immune evasion in hepatocellular carcinoma by increasing JAK1 mRNA translation.

Immunosuppression characterizes the tumour microenvironment in HCC, and recent studies have implicated RNA-binding proteins (RBPs) in the development of HCC. Here, we conducted a screen and identified RBM12 as a key protein that increased the expression of PD-L1, thereby driving immune evasion in HCC. Furthermore, RBM12 was found to be significantly upregulated in HCC tissues and was associated with a poor prognosis for HCC patients. Through various molecular assays and high-throughput screening, we determined that RBM12 could directly bind to the JAK1 mRNA via its 4th-RRM (RNA recognition motif) domain and recruit EIF4A2 through its 2nd-RRM domain, enhancing the distribution of ribosomes on JAK1 mRNA, which promotes the translation of JAK1 and the subsequent upregulation of its expression. As a result, the activated JAK1/STAT1 pathway transcriptionally upregulates PD-L1 expression, facilitating immune evasion in HCC. In summary, our findings provide insights into the significant contribution of RBM12 to immune evasion in HCC, highlighting its potential as a therapeutic target in the future. This graphical abstract shows that elevated expression of RBM12 in HCC can augment PD-L1-mediated tumour immune evasion by increasing the efficiency of JAK1 mRNA translation.

Prognostic Value of the Combination of HB (hemoglobin) and CEA in Resectable Gastric Cancer.

Objective: In order to investigate the prognostic value of a novel biomarker combining serum carcinoembryonic antigen (CEA) and hemoglobin (HB) levels in patients with resectable gastric cancer. Introduction: This retrospective study assessed the relationship between CEA, hemoglobin levels, a novel combined prognostic biomarker (HB-CEA) and clinicopathological features of gastric cancer. Their prognostic values in gastric cancer were also analyzed. Materials and Methods: This retrospective study evaluated the CEA, hemoglobin levels and clinicopathological features of patients with resectable gastric cancer. Kaplan-Meier curves, univariate and multivariate Cox proportional models were used to determine the prognostic significance of these factors for overall survival (OS) in the training and validation sets (n=353 and n=388, respectively). Based on optimal cutoff values of CEA and hemoglobin (3.395 ng/mL and 125.5 g/L, respectively), patients were stratified into three groups: HB-CEA=0, 1, and 2 (CEA <3.395 ng/mL and HB ≥125.5 g/L; CEA ≥3.395 ng/mL or HB <125.5 g/L; and CEA ≥3.395 ng/mL and HB <125.5 g/L, respectively). Results: The area under the curve was larger for HB-CEA than for either HB or CEA alone (training set: 0.677, 0.650, and 0.629; validation set: 0.670, 0.605, and 0.605, respectively). HB-CEA was strongly associated with age, tumor size, differentiation, pathological TNM stage (pTNM), depth of tumor invasion, lymph node metastasis, and survival status (all p<0.05). A higher HB-CEA score correlated with poor survival (Kaplan-Meier curves, all p<0.05). Multivariate analysis showed that HB-CEA was an independent prognostic factor for OS (p<0.05). Conclusion: Preoperative HB-CEA, as a potential novel hematological biomarker, can predict the progression of gastric cancer and the prognosis of patients, and is of great value in guiding clinical practice. Therefore, patients with a higher HB-CEA score should receive more extensive follow-up for early detection and intervention of tumor progression.

Pan-Cancer Analysis Predicts the Immunological and Prognostic Role of ZC3H12C in KIRC.

ZC3H12C is an important member of the CCCH-zinc finger protein family and is mainly involved in host immune and inflammatory diseases. However, its abnormal expression and prognostic value in cancer have not yet been established. Through comparative analysis of the Cancer Genome Atlas (TCGA) database, we found that ZC3H12C is the most relevant to the prognosis, grade, and stage of renal clear cell carcinoma (ccRCC) across 33 cancers. With the help of patient transcription and clinical data from the TCGA and GEO (GSE53757, GSE36895) databases, we determined that in the immune environment of patients with ccRCC, ZC3H12C was clearly negatively correlated with Tregs and was significantly positively correlated with monocytes. In addition, protein phosphorylation and DNA methylation analysis also showed that ZC3H12C negatively regulates the role of cancer in ccRCC. Our research may provide new insights into ccRCC immunotherapy and bring forth novel biomarkers and therapeutic targets.

A pan-cancer analysis of the oncogenic role of dual-specificity tyrosine (Y)-phosphorylation- regulated kinase 2 (DYRK2) in human tumors.

Although there have been studies correlating DYRK2 with a number of human cancers, there has been no pan-cancer analysis. Therefore, through the TCGA database, we conducted a related study on the expression of DYRK2 in cancers.The expression of DYRK2 is obviously increased in some cancers, while the opposite is true in others, and there is a clear association between its expression and the prognosis of cancer patients.The mutation of DYRK2 is also significantly correlated with patients' prognosis in certain human tumors. In addition, phosphorylation and methylation levels of DYRK2 are different between tumor tissues and adjacent normal tissues in various tumors. In the tumour microenvironment, the expression of DYRK2 correlates with cancer-associated fibroblast infiltration, such as BLCA or HNSC. In order to fully understand the role of DYRK2 in different tumors, we conducted a pan-cancer analysis.

Downregulation of promoter methylation gene PRDM5 contributes to the development of tumor proliferation and predicts poor prognosis in gastric cancer.

Background: Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Previous studies have shown that PRDM5 is methylated and silenced in GC. However, the role of PRDM5 in GC progression has not been explored. Methods: The expression and epigenetic alterations of PRDM5 in GC were analyzed in public datasets. The mRNA and protein expression of PRDM5 in fresh tissues were detected by semi-quantitative PCR and Western blot. And expression of PRDM5 in gastric paracarcinoma and carcinoma tissues from 162 patients was detected by immunohistochemistry (IHC) and assessed the association with different clinicopathological features. The prognostic value of PRDM5 in GC patients was evaluated using Kaplan-Meier plotter. We also studied promoter region methylation of PRDM5 in GC by methylation-specific PCR (MSP). The effects of PRDM5 on cell proliferation and migration were conducted by functional experiments in vitro. Results: The expression of PRDM5 was downregulated in GC, and that was associated with poor survival and tumor progression. And PRDM5 expression was found to be an independent prognostic factor for GC. We also found that the methylation of PRDM5 promoter was closely related to the histopathological types and the progression of tumors through the public relations database. In vitro, ectopical expression of PRDM5 inhibited the growth of tumor cells, while knockdown of PRDM5 increased the proliferation and migration of tumor cells. Conclusion: These results suggest that PRDM5 may be a novel TSG methylated in GC that plays important roles in GC development. And we found PRDM5 as a potential survival biomarker for GC, especially in well differentiated GC. PRDM5 expression was significantly correlated with tumor stage and histological type.