Background. The serum systemic inflammation biomarkers are known predictors of colorectal cancer (CRC) patient prognosis. However, their significance in human immunodeficiency virus (HIV)-infected patients with CRC has not been studied. To address this gap, we conducted a retrospective study to evaluate the prognostic value of preoperative systemic inflammation biomarkers in HIV-infected patients with CRC. Methods. The study enrolled 57 patients with colorectal cancer (CRC) and HIV who underwent surgery at the Shanghai Public Health Clinical Center between January 2015 and December 2021. Preoperative tests were conducted, and systemic inflammation biomarkers were measured. The patients were categorized into two groups using the optimal cut-off value. The Kaplan–Meier method and the log-rank test were used to determine overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional regression model. A time-dependent receiver operating characteristic (t-ROC) was used to compare the prognostic abilities of the biomarkers. Results. The study included 57 HIV-infected CRC patients, with a median age of 60 and a follow-up time ranging from 3 to 86 months. Of the patients, 49 were male and 8 were female. The cumulative three-year OS and PFS rates were 55.0% and 45.0%, respectively. The optimal cut-off value for preoperative NLR was found to be 2.8, which was significantly correlated with lower CD8+ T and CD3+ T lymphocyte counts. Multivariate Cox regression analysis revealed that a low NLR was an independent predictor of better OS and PFS (OS: HR = 0.094, 95% CI: 0.02–0.45, P = 0.003 ; PFS: HR = 0.265, 95% CI: 0.088–0.8, P = 0.019 ). The time-dependent receiver operating characteristic (t-ROC) analysis showed that NLR was a superior systemic inflammation biomarker for predicting the prognosis of HIV-infected CRC patients throughout the observation period. Conclusion. The preoperative neutrophil-to-lymphocyte ratio (NLR), an easily measurable immune biomarker, may provide useful prognostic information in HIV-infected colorectal cancer (CRC) patients.
The present study aimed to assess the anticancer cell and anticancer stem cell (CSC) effects of GANT61, and its regulatory influence on the Wnt/β-catenin and Notch signalling pathways in colorectal cancer (CRC). HT-29 and HCT-116 cells were treated with 0, 2.5, 5, 10, 20 or 40 µM GANT61, after which relative cell viability and the expression of Gli1, β-catenin and Notch1, as well as the percentage of CD133 + cells, were detected. Subsequently, HT-29/HCT-116 cells and CSCs were treated with 20 µM GANT61, 10 mM of the Wnt/β-catenin pathway agonist HLY78, and 30 mM of the Notch pathway agonist JAG1 (alone or in combination), which was followed by the assessment of cell viability and apoptosis. In both cell lines, GANT61 reduced relative cell viability in a time-and dose-dependent manner, inhibited Gli1, β-catenin and Notch1 expression, and decreased the percentage of CD133 + cells in a dose-dependent manner. Furthermore, HLY78 and JAG1 were both found to improve the relative viability, while downregulating the apoptosis of untreated and GANT61-treated HT-29 and HCT-116 cells. Moreover, Wnt/β-catenin and Notch signalling pathway activity were upregulated in CSCs isolated from HT-29 and HCT-116 cells, compared with the associated control groups. GANT61 also reduced the viability of HT-29 and HCT-116 cells and increased apoptosis, whereas HLY78 and JAG1 treatment resulted in the opposite effect. Moreover, both HLY78 and JAG1 attenuated the effects of GANT61 on cellular viability and apoptosis. In conclusion, GANT61 was found to effectively eliminate cancer cells and CSCs by blocking the Wnt/β-catenin and Notch signalling pathways in CRC.
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