Recently, we found that NHE9 mRNA was upregulated in chemoradiotherapy (CRT)-resistant esophageal squamous cell carcinoma (ESCC); however, the underlying mechanisms were unclear. Here, we aimed to clarify the functional contribution of NHE9 to CRT resistance, understand the molecular basis of NHE9-dependent resistance in ESCC, and identify potential therapeutic targets. Our results showed that NHE9 prevented CRT-induced apoptosis. Importantly, we found that RACK1 is a novel binding partner of NHE9 and that NHE9-dependent induction of CRT resistance requires the activation of RACK1-associated Src/Akt/β-catenin signaling. Moreover, upregulated Bcl-2 protein was also observed in cells exhibiting NHE9-induced CRT resistance. A higher NHE9 level was associated with a poor response to CRT and less decrease in T and N stage in ESCC patients. Furthermore, combining either Dasatinib or ABT-737 with CRT significantly reduced tumor volume, and the response to CRT was restored when these inhibitors were used together with CRT in a xenograft nude mouse model with NHE9 overexpression. Taken together, our findings demonstrate that NHE9 can be an effective predictor of CRT response and may be useful in the development of targeted therapies for CRT-resistant ESCC.
The present study aimed to investigate the feasibility of detecting p33 inhibitor of growth 1b (p33ING1b) gene methylation in fecal DNA as a screening method for colorectal carcinoma (CRC) and precancerous lesions. The methylation of p33ING1b was analyzed in fecal samples from 61 patients with CRCs, 27 patients with precancerous lesions (advanced adenoma) and 20 normal individuals by nested methylation-specific polymerase chain reaction (nMSP) and fecal occult blood test. Methylated p33ING1b was detected in 73.77% of CRC patients and 62.96% of adenoma patients. By contrast, only 5% of normal individuals had methylated p33ING1b. These results indicated 73.77% sensitivity for detecting CRC, 62.96% sensitivity for detecting precancerous lesions and 95% specificity of the assay for detecting CRCs and precancerous lesions. The detection of p33ING1b methylation status by incubation of DNA contained in agarose beads for bisulfite modification, followed by nMSP, is a promising non-invasive screening method for CRCs and precancerous lesions.
Background Disulfidptosis is a newly discovered mode of cell death. However, its relationship with breast cancer subtypes remains unclear. In this study, we aimed to construct a disulfidptosis-associated breast cancer subtype prediction model. Methods We obtained 19 disulfidptosis-related genes from published articles and performed correlation analysis with lncRNAs differentially expressed in breast cancer. We then used the random forest algorithm to select important lncRNAs and establish a breast cancer subtype prediction model. We identified 132 lncRNAs significantly associated with disulfidptosis (FDR < 0.01, |R|>0.15) and selected the first four important lncRNAs to build a prediction model (training set AUC = 0.992). Results The model accurately predicted breast cancer subtypes (test set AUC = 0.885). Among the key lncRNAs, LINC02188 had the highest expression in the Basal subtype, while LINC01488 and GATA3-AS1 had the lowest expression in Basal. In the Her2 subtype, LINC00511 had the highest expression level compared to other key lncRNAs. GATA3-AS1 had the highest expression in LumA and LumB subtypes, while LINC00511 had the lowest expression in these subtypes. In the Normal subtype, GATA3-AS1 had the highest expression level compared to other key lncRNAs. Our study also found that key lncRNAs were closely related to RNA methylation modification and angiogenesis (FDR < 0.05, |R|>0.1), as well as immune infiltrating cells (P.adj < 0.01, |R|>0.1). Conclusions Our random forest model based on disulfidptosis-related lncRNAs can accurately predict breast cancer subtypes and provide a new direction for research on clinical therapeutic targets for breast cancer.
Breast cancer prevalence has increased globally, with 12.2% of breast cancer cases identified in China. Obesity and unhealthy lifestyles are major risk factors for breast cancer. We conducted a randomized control trial to assess the feasibility and evaluate the preliminary effect of the Smartphone-Based Cancer and Obesity Prevention Education (SCOPE) program among adult biological women with a waist circumference greater than 80 cm. The SCOPE program includes tailored and culturally appropriate educational information for obesity and breast cancer prevention delivered by the research team via WeChat. The control group received non-tailored general health information via WeChat. A total of 102 women (52 intervention, 50 control) participated, and 87 (85%) completed 6-month follow-up assessments. For the primary study outcome at 6 months, women using SCOPE significantly reduced waist circumference (Cohen’s d = −0.39, p < 0.001). For secondary outcomes at 6 months, women using SCOPE significantly reduced BMI (d = −0.18, p = 0.001) and increased breast cancer-related knowledge (d = 0.48, p = 0.001) and attitude (d = 1.39, p < 0.01). No significant findings were found regarding diet self-efficacy, physical self-efficacy, or breast cancer screening barriers. The results suggest the intervention has great potential to promote the health and wellness of women.
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