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To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial-mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.
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BACKGROUND: Gastric cancer (GC) is a deadly tumor with the fifth highest occurrence and highest global mortality rates. Owing to its heterogeneity, the underlying mechanism of GC remains unclear, and chemotherapy offers little benefit to individuals. AIM: To investigate the clinical outcomes of TP53 and CDH1 mutations in GC. METHODS: In this study, 202 gastric adenocarcinoma tumor tissues and their corresponding normal tissues were collected. A total of 490 genes were identified using target capture. Through t-test and Wilcoxon rank-sum test, somatic mutations, microsatellite instability, and clinical statistics, including overall survival, were detected, compared, and calculated. RESULTS: The mutation rates of 32 genes, including TP53, SPEN, FAT1, and CDH1 exceeded 10%. TP53 mutations had a slightly lower overall occurrence rate (33%). The TP53 mutation rate was significantly higher in advanced stages (stage III/IV) than that in early stages (stage I/II) (P < 0.05). In contrast, CDH1 mutations were significantly associated with diffuse GC. TP53 is related to poor prognosis of advanced-stage tumors; nevertheless, CDH1 corresponds to a diffuse type of cancer. TP53 is exclusively mutated in CDH1 and is primarily affected by two distinct GC mechanisms. CONCLUSION: Different somatic mutation patterns in TP53 and CDH1 indicate two major mechanisms of GC.
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Socioeconomic deprivation has been linked to detrimental healthcare outcomes. We sought to examine whether patients with colorectal cancer (CRC) from socioeconomically disadvantaged areas experience worse survival outcomes and how it interacts with other factors. In this population-based study, patients with CRC diagnosed between 2007 to 2015 in the SEER program were reviewed. Socioeconomic deprivation was measured using the Area Deprivation Index (ADI) linked to patients' residence addresses. The effect of ADI on cancer-specific survival and overall survival was evaluated using survival analysis. The Inverse Probability of Weighted (IPW) method and multiple regression was performed to account for the confounding bias. Subgroup analyses were used to test interactions. Multiple mediation analysis was used to estimate the mediating effects. Overall, 266,620 eligible patients were included in further analyses. Compared with low ADI patients, high ADI patients had more unfavorable characteristics and worse cancer-specific (hazard ratio [HR] 1.14, 95% CI 1.12-1.16, P<.001) and overall survival (HR 1.11, 95% CI 1.09-1.12, P<0.001). The results were similar after accounting for confounding factors using the IPW and multiple regression methods. Subgroup analyses revealed the relative robustness of ADI as a prognostic factor. They detected significant interactions between ADI and other covariates on cancer survival, such as age, race, insurance status, disease stage, and receipt of treatment. Multiple mediation analyses identified several factors mediating survival disparities, including anticancer therapy, insurance status, race, marital status, and age. This study suggested that high ADI CRC patients were associated with more unfavorable characteristics at presentation and lower cancer and noncancer survival after treatment than their low ADI counterparts. Multiple factors interacted and mediated these survival disparities associated with the ADI.
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We conducted this meta-analysis to explore the association between passive smoking and the risk of colorectal cancer. A literature search of online databases, including MEDLINE, EMBASE, the Cochrane Library, and Web of Science was performed up to June 30, 2015. A fixed-effects meta-analysis using Stata 12.0 was carried out to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for the associations. Eleven articles, including 6 case-control studies and 6 cohort studies, were included in our analysis according to inclusion and exclusion criteria. The pooled RR of all studies showed a statistically significant association between passive smoking and colorectal cancer (RR = 1.14; 95% CI = 1.05-1.24). Results of subgroup analysis showed a positive association between passive smoking and rectal cancer ((RR = 1.33; 95% CI = 1.15-1.53) and that male passive smokers were at greater risks of colorectal cancer (RR = 1.73; 95% CI = 1.37-2.19) than females. Results suggested that passive smoking is associated with an increased risk of colorectal cancer.