Colorectal cancer is a commonly observed malignant cancer. However, the limited therapies for colorectal cancer do not bring much benefit for patients. Chondroitin synthase-1 (CHSY1) is an enzyme responsible for the biosynthesis of chondroitin sulfate and has been implicated in the tumorigenesis of several cancer types; however, there is limited information regarding the role of CHSY1 in colorectal cancer. In the present study, CHSY1 was demonstrated to be highly expressed in colorectal cancer tissues and in cell lines, and the CHSY1 expression level was associated with the 5-year survival rate of patients with colorectal cancer. Following CHSY1 knockdown, the proliferation of colorectal cancer cells was significantly decreased. The number of RKO cells decreased by 50% following CHSY1 knockdown compared with that in the control after culture for 5 days. However, the apoptosis rate of RKO cells increased to 14.15% after CHSY1 knockdown. In addition, the activity of caspase-3/7 was also enhanced. Furthermore, the expression of B-cell lymphoma 2 (Bcl-2) was reduced, whereas the levels of Bcl-2-associated X protein (Bax) and truncated caspase-3/7 were increased following CHSY1 knockdown. Additionally, the phosphorylation level of IκB and the expression of nuclear factor (NF) κB also decreased. In contrast, forced expression of CHSY1 increased the level of Bcl-2, NFκB, and phosphorylated IκB, whereas the level of bax and truncated caspase-3/7 decreased. Therefore, the data of the present study suggest that CHSY1 promoted cell proliferation by regulating NFκB signaling and suppressed cell apoptosis by regulating/caspase-3/7 signaling in colorectal cancer. The present study also suggests that CHSY1 may be a potential target for colorectal cancer therapy.
Preoperative radiation therapy has been regarded as the optional neoadjuvant treatment to decrease local recurrence of rectal cancer in addition to surgery. However, its benefit in survival remained obscure. This study was aimed to measure the efficacy of preoperative radiation therapy for survival in stage II and III rectal cancer patients. Retrospective cohort study used the database of Surveillance, Epidemiology and End Results program of the National Cancer Institute in the United States from 1988 to 2011. A total of 49,439 patients diagnosed with primary rectal cancer who underwent surgery were included. Clinicopathological characteristics and rectal cancer-specific survival between surgery alone group and surgery plus preoperative radiation therapy group were compared. Rectal cancer patients in surgery plus preoperative radiation therapy group had significantly better survival than those in surgery alone group (72.70% vs. 66.61%, p<0.001), as well as stratified by stages (stage II: 77.4% vs. 74.3%, p<0.001; stage III: 68.3% vs. 58.6%, p<0.001). However, this beneficial impact was only observed after 2000s (p<0.001). Multivariate survival analysis revealed that preoperative radiation therapy was an independent predictor for better survival in stage III (hazard ratio, 0.795; 95% CI, 0.753-0.840; p<0.001), but not in stage II (p=0.70). Preoperative radiation therapy might bring a better survival in stage II and III rectal cancer patients, but only as an independent predictor for stage III patients. As time progressed, preoperative radiation therapy might yield more profit for stage II and III rectal cancer patients.
BackgroundColorectal cancer (CRC) has become a heavy health burden around the world, accounting for about 10% of newly diagnosed cancer cases. In the present study, we aimed to establish the miRNA-based prediction signature to assess the prognosis of CRC patients.Material/MethodsA total of 451 CRC patients’ expression profiles and clinical information were download from the TCGA database. LASSO Cox regression was conducted to construct the overall survival (OS)- and recurrence-free survival (RFS)-associated prediction signatures, by which CRC patients were divided into low- and high-risk groups. Kaplan-Meier (K-M) curve and receiver operating characteristic (ROC) curves were used to explore the discriminatory ability and stability of the signatures. Functional enrichment analyses were performed to identify the probable mechanisms.ResultsmiRNA-216a, miRNA-887, miRNA-376b, and miRNA-891a were used to build the prediction formula associated with OS, while miR-1343, miR-149, miR-181a-1, miR-217, miR-3130-1, miR-378a, miR-542, miR-6716, miR-7-3, miR-7702, miR-677, and miR-891a were obtained to construct the formula related to RFS. K-M curve and ROC curve revealed the good discrimination and efficiency of OS in the training (P<0.001, AUC=0.712) and validation cohorts (P=0.019, AUC=0.657), as well as the results of RFS in the training (P<0.001, AUC=0.714) and validation cohorts (P=0.042, AUC=0.651). The function annotations for the targeted genes of these miRNAs show the potential mechanisms of CRC.ConclusionsWe established 2 novel miRNA-based prediction signatures of OS and RFS, which are reliable tools to assess the prognosis of CRC patients.
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