BackgroundFor many years, lung cancer has been the most common and deadly cancer worldwide. Early diagnosis of non‐small cell lung cancer (NSCLC) in particular is very difficult because the symptoms are often ignored. The five‐year survival rate is very low despite great improvements to therapy. Thus, there is an urgent need to identify prognostic biomarkers and target molecules for the clinical diagnosis and individualized treatment of NSCLC.MethodsWe performed quantitative real‐time PCR to determine the expression levels of the long non‐coding RNA (lncRNA) linc01433 in NSCLC and normal matched lung tissue. Subsequently, we established cell lines with overexpression or knockdown of linc01433 to evaluate the effects on proliferation and metastasis in vitro. Epithelial‐to‐mesenchymal transition was examined using Western blot.ResultsLinc01433 was significantly overexpressed in NSCLC tissues compared to normal lung tissues. In addition, linc01433 levels were associated with smoking history. Linc01433 overexpression in lung cancer cells increased proliferation, migration, and invasion abilities, as well as epithelial‐to‐mesenchymal transition.ConclusionsLinc01433 is a cancer‐related lncRNA that may have an oncogene‐like effect in NSCLC.

The sex difference in cancer occurrence is a consistent finding in cancer epidemiology. Several solid tumors, including lung cancer, colorectal cancer, hepatic carcinoma, and renal carcinoma, are generally more common in males. Although sexual dimorphism is attributed to hormonal or behavioral differences, evidence for the function of lncRNA is lacking in sex-specific cancers. We show here that LINC00263 is one of the most dysregulated lncRNAs in lung adenocarcinomas and is upregulated in lung adenocarcinoma, colorectal cancer, and renal carcinoma, especially in male patients compared to females. LINC00263 functions as an oncogene by promoting translocation of p65 into the nucleus to activate the NF-κB-signaling pathway through interaction with IKKα in the cytoplasm. The expression of LINC00263 is strongly correlated with ESR1, and it is decreased after treatment with estrogen. Ligand-activated ER could inhibit the function of LINC00263 by inhibiting NF-κB from cytoplasmic translocation into the nucleus. The inhibitory effect of estrogen on LINC00263 indicates its differential expression in male and female patients. Our findings indicate that LINC00263 is linked to male sex and estrogen as an oncogene, and these findings might help in the exploration of the mechanisms of differential gene regulation in sex-specific cancers.

IntroductionApproximately 30% of patients diagnosed with stage Ia-b NSCLC die of recurrent disease after surgery. This study aimed to identify immune-related biomarkers that might predict tumor recurrence in stage Ia-b NSCLC within 40 months after curative resection.MethodsGene expression data of stage Ia-b NSCLC samples was retrieved from the TCGA database, the GEO databases, and the Second Xiangya hospital (XXEYY) database. 22 types of tumors infiltrating immune cells and the expression of immune-associated genes were investigated using CIBERSORT, immunohistochemical staining, and GSEA analyses in a total of 450 patients (80 in the training cohort and 370 in the validation cohorts). Recurrence-related immune features were selected based on the LASSO Cox regression model.ResultsHigh density of Tregs, Macrophages M0 and M1 cell could be observed in recurrence group while the memory B cell was more frequently enriched in controls, yet Tregs alone was significantly associated with tumor early recurrence in TCGA cohort, XYEYY cohort and GSE37745 dataset. A handful of immune-related genes were identified in the recurrence group. Based on Lasso regression analysis, the expressions of five immune-related genes, RLTPR, SLFN13, MIR4500HG, HYDIN and TPRG1 were closely correlated with tumor early recurrence. In the training cohort (TCGA), the combination of these five genes has sensitivity and specificity of 85% and 85%, with AUC of 0.91 (95% CI 0.84-0.98) for lung cancer early recurrence prediction, whereas in validation cohorts, the sensitivity and specificity using this panel was 61-89% and 54-82%, with AUC of 0.62-0.84.ConclusionOur study demonstrated that the immune microenvironment signatures were closely related to tumor early recurrence. Compared to tumor-infiltrating lymphocytes, the expression of five immune-related genes could be robust biomarkers to predict early recurrence of stage Ia-b NSCLC after curative resection.

Background Diagnosing and treating synchronous multiple primary lung cancers (sMPLC) are complex and challenging. This study aimed to report real‐world data on the comprehensive diagnosis and treatment of patients with early‐stage sMPLC. Materials and Methods A single‐center cohort study was carried out and a large number of patients with early‐stage sMPLC were included. A single‐ or two‐stage surgery was performed to remove the primary and co‐existing lesions. The “X” strategies, including ablation, SBRT, and EGFR‐TKIs treatment, were applied to treat the high‐risk residual lesions. Wide panel‐genomic sequencing was performed to assess the genetic heterogeneity of the co‐existing lesions. Results A total of 465 early‐stage sMPLC patients with 1198 resected lesions were included. Despite most patients being histologically different or harboring different genetic alternations, about 7.5% of the patients had the same histological type and driver gene mutation changes, comprehensive re‐evaluation is thus needed. The “Surgery + X” strategy showed remarkable efficacy and safety in treating multiple lesions. Follow‐up data revealed that the T2 stage (p = 0.014) and the solid presence of a primary lesion (p < 0.001) were significantly related to tumor recurrence. And a T2‐stage primary tumor had a significantly higher rate of developing new lesions after the initial surgery (p < 0.001). Conclusions In real‐world practice, histopathological and radiological evaluation combined with genetic analyses could be a robust diagnostic approach for sMPLC. The “Surgery + X” treatment strategy showed remarkable efficacy, superiority, and safety in the clinical treatment of early‐stage sMPLC.