ABSTRACT
Long non-coding RNA (lncRNA) is associated with a large number of tumor cellular functions together with chemotherapy resistance in a variety of tumors. LINC00963 was identified to regulate the malignant progression of various cancers. However, whether LINC00963 affects drug resistence in esophageal squamous cell carcinoma (ESCC) and the relevant molecular mechanisms have never been reported. This study aims to investigate the effect of LINC00963 on cisplatin resistance in ESCC. After detecting the level of LINC00963 in human esophageal squamous epithelial cells (HET-1 A), ESCC cells (TE-1) and cisplatin resistant cells of ESCC (TE-1/DDP), TE-1/DDP cell line and nude mouse model that interfered with LINC00963 expression were established. Then, the interaction among LINC00963, miR-10a, and SKA1 was clarified by double luciferase and RNA immunoprecipitation (RIP) assays. Meanwhile, the biological behavior changes of TE-1/DDP cells with miR-10a overexpression or SKA1 silencing were observed by CCK-8, flow cytometry, scratch, Transwell, and colony formation tests. Finally, the biological function of the LINC00963/SKA1 axis was elucidated by rescue experiments. LINC00963 was upregulated in TE-1 and TE-1/DDP cell lines. LINC00963 knockdown inhibited SKA1 expression of both cells and impaired tumorigenicity. Moreover, LINC00963 has a target relationship with miR-10a, and SKA1 is a target gene of miR-10a. MiR-10a overexpression or SKA1 silencing decreased the biological activity of TE-1/DDP cells and the expression of SKA1. Furthermore, SKA1 overexpression reverses the promoting effect of LINC00963 on cisplatin resistance of ESCC. LINC00963 regulates TE-1/DDP cells bioactivity and mediates cisplatin resistance through interacting with miR-10a and upregulating SKA1 expression.
ABSTRACT
BACKGROUND: Maintenance therapy (MT) for recurrent or metastatic cervical cancer remains non-standardized. This study assessed MT effectiveness using a comprehensive approach and identifies prognosis factors inpatients with recurrent or metastatic cervical cancer. METHODS: From January 2019 and December 2021, over 6000 patients from six Chinese institutions were retrospectively examined. Patients had recurrent/metastatic cervical cancer and underwent first-line chemotherapy with or without MT. We calculated overall and progression-free survival using Kaplan-Meier analysis, comparing via log-rank test, and conducted Cox regression for prognostic factors. RESULTS: Overall, 274 patients were stratified into an MT group (n = 77) and a non-MT group (n = 197). The 3-year OS rates were 52.5 % and 28.0 % for the MT and non-MT groups, respectively. The MT group had significantly enhanced median OS (37 vs. 21 months; HR, 0.43; 95 % CI, 0.30-0.61; P < 0.001) and PFS (21 vs. 14 months; HR, 0.65; 95 % CI, 0.47-0.90; P = 0.014) compared with the non-MT group. No significant differences in efficacy were observed among the various MT regimens, whether PD-1 monoclonal antibody, targeted therapeutic agents, or a combination of both. Extended PFS and OS were observed in patients receiving > 8 MT cycles. Multivariate analyses revealed that oligometastasis, MT, exclusive prior surgery (as opposed to combined surgery and radiotherapy), and extended interval before recurrence were independent OS predictors (P = 0.045, P < 0.001, P = 0.010, and P = 0.005, respectively); oligometastasis, concurrent radiotherapy, MT, and extended interval before recurrence were independent PFS predictors (P = 0.004, P = 0.007, P = 0.009, and P = 0.003). CONCLUSIONS: The MT integration markedly extended PFS and OS in patients diagnosed with recurrent or metastatic cervical cancer.
Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Progression-Free SurvivalABSTRACT
Background: Postoperative pulmonary complications (PPCs) significantly increase the morbidity and mortality in elderly patients with lung cancer. Considering the adverse effects of PPCs, we aimed to derive and validate a nomogram to predict pulmonary complications after video-assisted thoracoscopic surgery in elderly patients with lung cancer and to assist surgeons in optimizing patient-centered treatment plans. Methods: The study enrolled 854 eligible elderly patients with lung cancer who underwent sub-lobectomy or lobectomy. A clinical prediction model for the probability of PPCs was developed using univariate and multivariate analyses. Furthermore, data from one center were used to derive the model, and data from another were used for external validation. The model's discriminatory capability, predictive accuracy, and clinical usefulness were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis, respectively. Results: Among the eligible elderly patients with lung cancer, 214 (25.06%) developed pulmonary complications after video-assisted thoracoscopic surgery. Age, chronic obstructive pulmonary disease, surgical procedure, operative time, forced expiratory volume in one second, and the carbon monoxide diffusing capacity of the lung were independent predictors of PPCs and were included in the final model. The areas under the ROC curves (AUC) of the training and validation sets were 0.844 and 0.796, respectively. Ten-fold cross-validation was used to evaluate the generalizability of the predictive model, with an average AUC value of 0.839. The calibration curve showed good consistency between the observed and predicted probabilities. The proposed nomogram showed good net benefit with a relatively wide range of threshold probabilities. Conclusion: A nomogram for elderly patients with lung cancer can be derived using preoperative and intraoperative variables. Our model can also be accessed using the online web server https://pulmonary-disease-predictor.shinyapps.io/dynnomapp/. Combining both may help surgeons as a clinically easy-to-use tool for minimizing the prevalence of pulmonary complications after lung resection in elderly patients.
ABSTRACT
Objectives: To evaluate the short-term outcomes of uniportal video-assisted thoracoscopic surgery (UVATS) and Da Vinci robot-assisted thoracoscopic surgery (RATS) in lobectomy and lymph node (LN) dissection. Methods: The two groups of patients with primary non-small cell lung cancer (NSCLC; RATS group, UVATS group) were matched by the propensity score to compare LN dissection and recent clinical outcomes. The results were analyzed by univariate analysis. From November 2020 to November 2021, 412 NSCLC patients (54 RATS and 358 UVATS) from a single institution of the Provincial Hospital affiliated with Shandong First Medical University were included in the analysis. Age, sex, lung lobe, surgical resection scope, solid nodules, and core tumor ratios were matched according to different surgical methods. Results: From November 2020 to November 2021, 412 patients with NSCLC (54 RATS, 358 UVATS) from the Provincial Hospital affiliated with Shandong First Medical University were included in the analysis. According to our matching results, LN dissection was more thorough in the RATS group. Conclusion: RATS has potential advantages over UVATS in radical lung cancer surgery.
