Hepatitis B virus (HBV) infection is associated with hepatitis and hepatocellular carcinoma (HCC). Considering that most HBV-infected individuals remain asymptomatic, the mechanism linking HBV to hepatitis and HCC remains uncertain. Herein, we demonstrate that HBV alone does not cause liver inflammation or cancer. Instead, HBV alters the chronic inflammation induced by chemical carcinogens to promote liver carcinogenesis. Long-term HBV genome expression in mouse liver increases liver inflammation and cancer propensity caused by a carcinogen, diethylnitrosamine (DEN). HBV plus DEN-activated interleukin-33 (IL-33)/regulatory T cell axis is required for liver carcinogenesis. Pitavastatin, an IL-33 inhibitor, suppresses HBV plus DEN-induced liver cancer. IL-33 is markedly elevated in HBV⁺ hepatitis patients, and pitavastatin use significantly correlates with reduced risk of hepatitis and its associated HCC in patients. Collectively, our findings reveal that environmental carcinogens are the link between HBV and HCC risk, creating a window of opportunity for cancer prevention in HBV carriers.

Background and Objectives: RAD51 plays an essential role in DNA repair via homologous recombination. RAD51 facilitates strand transfer between interrupted sequences and their undamaged homologies. Therefore, we studied the RAD51 mRNA expression levels in colorectal cancer (CRC), and evaluated the clinicopathological and prognostic significance of RAD51. Materials and Methods: The RAD51 expression was examined in 48 CRCs and paired adjacent non-tumor tissues. We further evaluated the survival to determine the prognostic value of RAD51 in our CRC and The Cancer Genome Atlas (TCGA) data. Results: We confirmed that the RAD51 expression in tumor tissues, compared with that of paired non-tumor tissues, was upregulated 2.5-fold. Additionally, the RAD51 expression was significantly associated with the T stage (p = 0.027). According to a higher T stage, the RAD51 expression showed an increasing trend. However, the RAD51 expression did not show a prognostic value statistically. Conclusions: We confirmed that RAD51 was upregulated in tumors and was significantly associated with the T stage. Although there was no statistically significant prognostic value found in our samples and TGCA data, our study will provide new insight for RAD51 in CRC.

Background and Objectives: The gene NKX3.2 plays a role in determining cell fate during development, and mutations of NKX3.2 have been studied in relation to human skeletal diseases. However, due to the lack of studies on the link between NKX3.2 and cancer, we aimed to provide insights into NKX3.2 as a new prognostic biomarker for liver hepatocellular carcinoma (LIHC). Materials and Methods: The clinical significance of LIHC was investigated using open gene expression databases. We comprehensively analyzed NKX3.2 expression in LIHC using Gene Expression Profiling Interactive Analysis 2, Tumor Immune Estimation Resource (TIMER), and Kaplan–Meier plotter databases. Then, we investigated the association between NKX3.2 expression and tumor-infiltrating immune cells (TIICs). Results: NKX3.2 expression was higher in the primary tumor group compared to the normal group, and expression was higher in fibrolamellar carcinoma (FLC) compared to other subtypes. When the prognostic value of NKX3.2 was evaluated, highly expressed NKX3.2 significantly improved the overall survival and had an unfavorable prognosis. In addition, NKX3.2 expression was associated with immune cell infiltration. Patients with low gene expression and high macrophage expression had a poorer survival rate than those with low NKX3.2 and low macrophage expression (p = 0.0309). Conclusions: High NKX3.2 expression may induce poorer prognosis in LIHC. In addition, these findings can be used as basic data due to the lack of available related research. However, further in vivo studies are essential to gain a deeper understanding of the biological role of NKX3.2 in LIHC and its potential implications for cancer development and progression.

Background and objectives: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is caused by multiple factors. To explore novel targets for HCC treatment, we comprehensively analyzed the expression of HomeoboxB13 (HOXB13) and its role in HCC. Materials and Methods: The clinical significance of HCC was investigated using open gene expression databases, such as TIMER, UALCAN, KM, OSlihc, and LinkedOmics, and immunohistochemistry analysis. We also analyzed cell invasion and migration in HCC cell lines transfected with HOXB13-siRNA and their association with MMP9, E2F1, and MEIS1. Results: HOXB13 expression was higher in fibrolamellar carcinoma than in other histological subtypes. Its expression was associated with lymph node metastasis, histological stage, and tumor grade. It was positively correlated with immune cell infiltration of B cells (R = 0.246), macrophages (R = 0.182), myeloid dendritic cells (R = 0.247), neutrophils (R = 0.117), and CD4+ T cells (R = 0.258) and negatively correlated with immune cell infiltration of CD8+ T cells (R = −0.107). A positive correlation was observed between HOXB13, MMP9 (R = 0.176), E2F1 (R = 0.241), and MEIS1 (R = 0.189) expression (p < 0.001). The expression level of HOXB13 was significantly downregulated in both HepG2 and PLC/PFR/5 cell lines transfected with HOXB13-siRNA compared to that in cells transfected with NC siRNA (p < 0.05). Additionally, HOXB13 significantly affected cell viability and wound healing. Conclusions: HOXB13 overexpression may lead to poor prognosis in patients with HCC. Additional in vivo studies are required to improve our understanding of the biological role and the exact mechanism of action of HOXB13 in HCC.

Background and Objectives: Transient receptor potential melastatin 7 (TRPM7) is a unique channel protein, and functionally responsible for transportation of calcium and magnesium. Physiologically, the TRPM7 channel is involved in homeostasis of calcium and magnesium, and cell survival. TRPM7 expression is up-regulated in many cancers as malignant behaviors of cancer cells, and its deficiency suppresses their growth. Materials and Methods: In this study, we aimed to analyze clinical and prognostic characteristics of TRPM7 expression in colorectal cancers (CRC) using The Cancer Genome Atlas. Results: High expression of TRPM7 was observed in younger patients with rectal cancer (p = 0.0002). By quantitative correlation analysis, TRPM7 was negatively correlated with age (R = −0.239, p = 0.003) and p53 (R = −0.240, p = 0.002). Furthermore, it was positively correlated with APC expression (R = 0.534, p < 0.001) and KRAS expression (R = 0.319, p < 0.001). In colon cancer, there were no variables that showed a significant correlation with TRPM7. Survival analysis found that TRPM7 expression did not have any prognostic value in colon and rectal cancers. Conclusions: Our study highlights that TRPM7 expression in CRC, particularly in rectal cancer, may be a potential marker. Future studies are needed to provide deeper insights into the role of TRPM7 in rectal cancer.

Background: Pancreatic cancer, while relatively uncommon, is extrapolated to become the second leading cause of cancer-related deaths worldwide. Despite identifying well-known markers like the KRAS gene, the exact regulation of pancreatic cancer progression remains elusive. Methods: Clinical value of PRC1 was analyzed using bioinformatics database. The role of PRC1 was further evaluated through cell-based assays, including viability, wound healing, and sensitivity with the drug. Results: We demonstrate that PRC1 was significantly overexpressed in pancreatic cancer compared to pancreases without cancer, as revealed through human databases and cell lines analysis. Furthermore, high PRC1 expression had a negative correlation with CD4+ T cells, which are crucial for the immune response against cancers. Additionally, PRC1 showed a positive correlation with established pancreatic cancer markers. Silencing PRC1 expression using siRNA significantly inhibited cancer cell proliferation and viability and increased chemotherapeutic drug sensitivity. Conclusions: These findings suggest that targeting PRC1 in pancreatic cancer may enhance immune cell infiltration and inhibit cancer cell proliferation, offering a promising avenue for developing anticancer therapies.