MicroRNAs (miRNAs) have been reported to play crucial roles in regulating a variety of genes pivotal for tumor metastasis. MicroRNA-301a (miR-301a) is overexpressed and displays oncogenic activity in many cancers. However, little is known about the potential roles of miR-301a in colorectal cancer (CRC). Taqman probe stem-loop real-time PCR was used to quantitatively measure the expression level of miR-301a in 48 cases of CRC tissues and the matched adjacent non-tumor mucosa as well as in CRC cell lines. miR-301a mimics and inhibitors were used to up-regulate and down-regulate miR-301a in CRC cells, respectively; lentivirus was used to construct miR-301a stably up- and down-regulated CRC cell lines. Metastasis ability was evaluated by transwell and wound healing assays while invasion was measured by transwell coated with matrix gel in vitro; in vivo metastasis was performed on nude mice model. The target of miR-301a was predicted by TargetScan software and validated by qRT-PCR, immunohistochemistry, western blot and luciferase reporter gene assay. The expression of miR-301a was significantly higher in lymph node metastasis positive CRC samples compared with negative ones. Downregulation of miR-301a significantly inhibited the migration and invasion both in vitro and in vivo while forced up-regulation of miR-301a promoted migration and invasion. TGFBR2 was identified to be the downstream target of miR-301a. Knockdown of TGFBR2 in cells treated by miR-301a inhibitor elevated the previously abrogated migration and invasion. Our data indicated that miR-301a correlated with the metastatic and invasive ability in human colorectal cancers and miR-301a exerted its role as oncogene by targeting TGFBR2.

The long-term survival and perioperative outcomes of robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) in resectable non-small-cell lung cancer (NSCLC) were found to be comparable in retrospective studies, but they have not been investigated in a randomized trial setting. We conducted the RVlob trial to investigate if RAL was non-inferior to VAL in patients with resectable NSCLC. In this single-center, open-label, and parallel-arm randomized controlled trial conducted in Ruijin Hospital (Shanghai, China) between May 2017 and May 2020, we randomly assigned patients with resectable NSCLC in a 1:1 ratio to receive either RAL or VAL. One of the primary endpoints was 3-year overall survival. Secondary endpoints included 3-year disease-free survival. The Kaplan–Meier approach was used to calculate overall survival and disease-free survival at 3 years. This study was registered with ClinicalTrials.gov, NCT03134534. A total of 320 patients were randomized to receive RAL (n = 157) or VAL (n = 163). The baseline characteristics of patients were well balanced between the two groups. After a median follow-up of 58.0 months, the 3-year overall survival was 94.6% (95% confidence interval [CI], 91.0–98.3) in the RAL group and 91.5% (95% CI, 87.2–96.0) in the VAL group (hazard ratio [HR] for death, 0.65; 95% CI, 0.33–1.28; P = 0.21); noninferiority of RAL was confirmed according to the predefined margin of −5% (absolute difference, 2.96%; a one-sided 90% CI, −1.39% to ∞; P = 0.0029 for noninferiority). The 3-year disease-free survival was 88.7% (95% CI, 83.6–94.1) in the RAL group and 85.4% (95% CI, 80.0–91.2) in the VAL group (HR for disease recurrence or death, 0.87; 95% CI, 0.50–1.52; P = 0.62). This study is the first randomized trial to show that RAL resulted in non-inferior overall survival compared with VAL in patients with resectable NSCLC. Based on our results, RAL is an equally oncologically effective treatment and can be considered as an alternative to VAL for resectable NSCLC. 10.13039/501100001809 National Natural Science Foundation of China (82072557), 10.13039/501100012166 National Key Research and Development Program of China (2021YFC2500900), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20172005, the 2nd round of disbursement), program of 10.13039/501100012247 Shanghai Academic Research Leader from 10.13039/501100003399 Science and Technology Commission of Shanghai Municipality (20XD1402300), Novel Interdisciplinary Research Project from 10.13039/100017950 Shanghai Municipal Health Commission (2022JC023), and Interdisciplinary Program of 10.13039/501100004921 Shanghai Jiao Tong University (YG2023ZD04).

Lung cancer, the leading cause of cancer-related mortality globally, exhibits remarkable histological plasticity, with non-small cell lung cancer (NSCLC) frequently transforming into small cell lung cancer (SCLC) as a resistance mechanism to targeted therapies and immunotherapies. The molecular mechanisms and treatments for SCLC transformation remain unclear. This review analyzes the mechanisms, molecular features, and treatment landscape of histological transformation, particularly in EGFR-mutant NSCLC. Key findings include: (1) RB1 and TP53 co-inactivation is a hallmark of transformed SCLC, enabling lineage plasticity via epigenetic and neuroendocrine changes; (2) the tumor immune microenvironment becomes immunosuppressive during transformation; and (3) new therapies targeting DLL3 and AURKA show promise in early trials. This study offers a comprehensive framework to understand histological transformation in lung cancer. It underscores the importance of routine re-biopsies for early detection and supports the development of biomarker-guided therapies. Future research should validate predictive biomarkers and optimizing combination therapies for transformed SCLC.

Background: New clinically important postoperative atrial fibrillation (POAF) is the most common arrhythmia after thoracoscopic anatomical lung cancer surgery and is associated with increased morbidity and mortality. The full spectrum of predictors remains unclear, and effective assessment tools are lacking. This study aimed to develop and externally validate a novel model for predicting new clinically important POAF. Methods: This retrospective study included 14 074 consecutive patients who received thoracoscopic anatomical lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital. Based on the split date of 1 January 2018, we selected 8717 participants for the training cohort and 5357 participants for the testing cohort. For external validation, we pooled 2941 consecutive patients who received this surgical treatment from July 2016 to July 2021 in Shanghai Ruijin Hospital. Independent predictors were used to develop a model and internally validated using a bootstrap-resampling approach. The area under the receiver operating characteristic curves (AUROCs) and Brier score were performed to assess the model discrimination and calibration. The decision curve analysis (DCA) was used to evaluate clinical validity and net benefit. New clinically important POAF was defined as a new-onset of POAF that causes symptoms or requires treatment. Results: Multivariate analysis suggested that age, hypertension, preoperative treatment, clinical tumor stage, intraoperative arrhythmia and transfusion, and operative time were independent predictors of new clinically important POAF. These seven candidate predictors were used to develop a nomogram, which showed a concordance statistic (C-statistic) value of 0.740 and good calibration (Brier score; 0.025). Internal validation revealed similarly good discrimination (C-statistic, 0.736; 95% CI: 0.705–0.768) and calibration. The decision curve analysis showed positive net benefits with the threshold risk range of 0–100%. C-statistic value and Brier score were 0.717 and 0.028 in the testing cohort, and 0.768 and 0.012 in the external validation cohort, respectively. Conclusions: This study identified seven predictors of new clinically important POAF, among which preoperative treatment, intraoperative arrhythmia, and operative time were rarely reported. The established and externally validated model has good performance and clinical usefulness, which may promote the application of prevention and treatment in high-risk patients, and reduce the development and related adverse outcomes of this event.

Background: Lung cancer is the leading cause of cancer-related death worldwide, and the timely and serial assessment of low-dose computed tomography (LDCT) in high-risk populations remains a challenge. Furthermore, testing a single biomarker for the diagnosis of lung cancers is of relatively low effectiveness. Thus, a stronger diagnostic combination of blood biomarkers is needed to improve the diagnosis of non-small cell lung cancer (NSCLC). Methods: The blood levels of individual biomarkers [IDH1, DNA methylation of short stature homeobox 2 gene (SHOX2), and prostaglandin E receptor 4 gene (PTGER4)] were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. In total, 221 candidates were enrolled and randomly assigned into two groups for the training and validation of a diagnostic panel. Additionally, a subgroup analysis was performed in the whole cohort. Results: A newly combined 3-marker diagnostic model for lung cancers was established and validated with area under the receiver operating characteristic (ROC) curve (AUC) values ranging from 0.835 to 0.905 in independent groups showing significantly stronger diagnostic value compared with a single tested biomarker. The sensitivity of the diagnostic model was as high as 86.1% and 80.0% in the training and validation sets, respectively. Although no apparent differences were found between the 3-marker and 2-marker models, the high clinical T-stage and histological type specificity of IDH1 and two other methylated DNA biomarkers were demonstrated in the subgroup analysis. Conclusions: The combination of single biomarkers with high stage-specificity and histological type specificity (SHOX2 and PTGER4 DNA methylation and IDH1) showed better diagnostic performance in the detection of lung cancers compared with single marker assessment. A greater clinical utility of the panel may be developed by adding demographic/epidemiologic characteristics.

Secreted clusterin (sCLU), a 75–80 kDa disulfide-linked heterodimeric protein, plays crucial roles in various pathophysiological processes, including lipid transport, tissue remodeling, cell apoptosis and reproduction. Our previous studies demonstrated that sCLU could influence cell apoptosis, proliferation, and invasion of non-small cell lung cancer (NSCLC) cells. In this study, clusterin’s function in regulating transdifferentiation of NSCLC cells was investigated. In addition, we examined the correlation between clusterin and clinicopathological features of lung cancer. We found that clusterin was increased in lung adenocarcinoma tissues and decreased in lung squamous cell carcinoma tissues through immunohistochemical technique. In cultured lung adenocarcinoma cell lines, clusterin addition could increase SP-C protein expression in 2.75-fold, and decrease p63 protein expression in 0.65-fold (1.54 to 1). And also clusterin addition could increase SP-C mRNA expression in 4.05-fold, decreased p63 mRNA expression in 0.51-fold. Our study demonstrated that clusterin could promote EMT and influence transdifferentiation from lung squamous cell carcinoma to lung adenocarcinoma. However, we found that clusterin expression have no correlation with malignance associate clinicopathological data. Our study may help to further elucidate the development and progression of NSCLC, also it may contribute to the research of therapies targeting sCLU.