Background: Cervical squamous cell cancer (CESC) is a common malignancy tumor with high incidence and mortality in women globally. Increasing studies have indicated that there was an indivisible association between alternative mRNA splicing (AS) and multiple types of cancer. However, comprehensive analysis of alternative mRNA splicing events is scarce in CESC. Methods: In this study, alternative mRNA splicing events data and clinical information of 216 CESC patients were downloaded from TCGA SpliceSeq database and TCGA website. We used identified survival-associated splicing events (SASEs) to construct prognostic signatures. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve were performed to evaluate the clinical value of prognostic signatures. A nomogram was carried out to quantitatively predict individuals’ survival probability. Regulatory network between splicing factors (SFs) and SASE was analyzed to explore the upstream regulators of a certain SASE. Additionally, we explored potential downstream pathways of a certain SASE. Results: A total of 41776 alternative splicing events in 9961 genes were collected. After sorting out SASEs, multivariable regression analysis was used to acquire 70 SASEs that could be independent prognostic factors for overall survival in CESC. Kaplan-Meier survival analyses showed that the difference was statistically significant (P<0.01). The area under ROC curve (AUC) for all AS pattern was 0.932. A nomogram was constructed with a concordance index of 0.82 to predict individuals’ survival probability. EIF3A positively regulated SEC23A-27346-AP with highest correlation coefficient (P<0.001, R=0.69). Besides, the most significant SASEs and KEGG pathways were SEC23A-27346-AP and adherens junction pathway (P=0.02, R=0.65). Conclusions: Prognostic signatures of survival-associated splicing events were independent prognostic factors for overall survival among CESC patients. A nomogram could quantitatively predict individuals’ survival probability. Moreover, we proposed that splicing factor EIF3A positively regulated SEC23A-27346-AP, and adherens junction pathway may be the downstream pathway of SEC23A-27346-AP. The aforementioned signaling pathway could play a crucial role in the development of CESC.
Background: Few studies have suggested the correlation between intraoperative dexamethasone and oncological outcomes in non-small cell lung cancer (NSCLC) patients with radical resection. The existing data are inconsistent and inadequate, and more evidence is needed. We therefore undertook a propensity-matched cohort study to investigate the correlation. Methods: 832 patients with stage I to IIIa NSCLC who went through a curative resection between January 2008 and December 2013 were enrolled in our study. Propensity-score matching analysis created a population of 206 patients in the non-DEX group and 103 patients in the DEX group. Cox regression analyses were applied to compare the disease-free survival (DFS) and overall survival (OS) between patients who did not and did receive dexamethasone in the propensity score-matched cohort, as well as in the certain patients with high-risk factors of postoperative nausea and vomiting. Results: After propensity score matching, intraoperative dexamethasone was not significantly associated with DFS (HR: 1.014, 95%CI: 0.786-1.309, P = 0.913) and OS (HR: 1.221, 95%CI: 0.905-1.647, P = 0.191). Multivariable cox regression analysis revealed that intraoperative dexamethasone was not still associated with DFS and OS after curative resection for NSCLC. In the subgroup analysis, intraoperative dexamethasone was significantly associated with improved DFS (HR: 0.20, 95%CI: 0.04-0.92, P = 0.038) in the group of anesthetic time less than 2 hours. In the subgroup of VATS, intraoperative dexamethasone was significantly associated with prolonged OS (HR: 0.53, 95%CI: 0.30-0.92, P = 0.023). Conclusion: There was no correlation between intraoperative administration of dexamethasone and survival in NSCLC patients after curative surgery. While patients given intraoperative dexamethasone had better disease-free survival compared with patients not given intraoperative dexamethasone in the subgroup of anesthetic time less than 2 hours. Intraoperative administration of dexamethasone may improve overall survival in the subgroup of VATS. Our results indicate that intraoperative administration of dexamethasone is probably favorable in the aforementioned populations.
Background: Few studies have suggested the correlation between intraoperative dexamethasone and oncological outcomes in non-small cell lung cancer (NSCLC) patients with radical resection. The existing data are inconsistent and inadequate, and more evidence is needed. We therefore undertook a propensity-matched cohort study to investigate the correlation.Methods: 832 patients with stage I to IIIa NSCLC who went through lung tumor resection between January 2008 and December 2013 were enrolled in our study. Propensity-score matching analysis created a population of 260 patients in the non-DEX group and 130 patients in the DEX group. Cox regression analyses were applied to compare the disease-free survival (DFS) and overall survival (OS) between patients who did not and did receive dexamethasone in the propensity score-matched cohort, as well as in the certain patients with high-risk factors of postoperative nausea and vomiting (PONV).Results: After propensity score matching, intraoperative dexamethasone was not significantly associated with DFS (HR: 0.944, 95%CI: 0.720-1.237, P = 0.655) and OS (HR: 1.210, 95%CI: 0.927-1.581, P = 0.486). Multivariable cox regression analysis revealed that intraoperative dexamethasone was not independent prognostic factor for DFS and OS in NSCLC patients undergoing surgical resection. In the subgroup analysis, including female subgroup, nonsmoking subgroup, long anesthetic time subgroup, VATS subgroup and inhaled anesthetics subgroup, intraoperative dexamethasone was not significantly associated with DFS and OS.Conclusion: There was no correlation between intraoperative administration of dexamethasone and survival in NSCLC patients after curative surgery. In the high-risk subgroups of PONV, that is, female, nonsmoking, long anesthetic time, VATS and inhaled anesthetics, patients given intraoperative dexamethasone had no better or poorer prognosis compared with patients not given intraoperative dexamethasone.
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