DHX37 Is a Promising Prognostic Biomarker and a Therapeutic Target for Immunotherapy and Chemotherapy in HCC

SIMPLE SUMMARY: The DEAD/H-box RNA helicase family is widely involved in tumor progression. Previously, many studies have found that DHX9, DHX15, DDX24, DHX29, etc. are widely involved in tumor progression through various pathways, however, the role of DHX37, as an important member of the DEAD/H-box RNA helicase family, in hepatocellular carcinoma progression has been less studied. In this study, we analyzed the expression of DHX37 in hepatic hepatocellular carcinoma (HCC), its correlation with clinicopathological features, potential prognostic value, and the effect of DHX37 expression on chemotherapy and immunotherapy of hepatocellular carcinoma by using bioinformatics tools such as GDSC, HPA, STRING, TISCH, and TIMER2. Clinical HCC samples were used to validate DHX37 expression in HCC and the correlation between DHX37 expression and immune cell infiltration. Our study suggests that DHX37 is a novel prognostic marker for hepatocellular carcinoma and is valuable for predicting response to chemotherapy and immunotherapy. ABSTRACT: DHX37, a member of the DEAD/H-box RNA helicase family, has been implicated in various diseases, including tumors. However, the biological characteristics and prognostic significance of DHX37 in HCC remain unclear. In this study, we use R software 3.6.3 and multiple bioinformatics analysis tools, such as GDSC, HPA, STRING, TISCH, and TIMER2, to analyze the characterization and function of DHX37 in HCC. In addition, Western blot (WB) and immunohistochemistry (IHC) based on clinical samples validated some of the findings. DHX37 was more highly expressed in HCC samples compared to adjacent non-tumor tissues. Higher DHX37 expression is correlated with various clinicopathological characteristics in HCC, including AFP, adjacent hepatic tissue inflammation, histologic grade, T stage, and pathologic stage. Survival analysis revealed that the high DHX37 group had significantly shorter overall survival (OS), progress-free interval (PFI), and disease-specific survival (DSS) compared to the low DHX37 group. By analyzing the correlation between DHX37 and the IC50 of chemotherapeutic drugs, the results showed that DHX37 expression level was negatively correlated with the IC50 of 11 chemotherapeutic drugs. Further analysis indicated that DHX37 and its co-expressed genes may play important roles in activating the cell cycle, DNA repair, chemokine signaling pathways, and regulating the immune response, which leads to a poor prognosis in HCC. High expression of DHX37 is an independent risk factor for poor prognosis in HCC, and DHX37 is expected to be a potential target to inhibit tumor progression. Targeting DHX37 may enhance chemotherapeutic drug sensitivity and immunotherapeutic efficacy in HCC.