A gene-based survival score for lung adenocarcinoma by multiple transcriptional datasets analysis.

BACKGROUND: Lung adenocarcinoma (LUAD) remains a crucial factor endangering human health. Gene-based clinical predictions could be of great help for cancer intervention strategies. Here, we tried to build a gene-based survival score (SS) for LUAD via analyzing multiple transcriptional datasets. METHODS: We first acquired differentially expressed genes between tumors and normal tissues from intersections of four LUAD datasets. Next, survival-related genes were preliminarily unscrambled by univariate Cox regression and further filtrated by LASSO regression. Then, we applied PCA to establish a comprehensive SS based on survival-related genes. Subsequently, we applied four independent LUAD datasets to evaluate prognostic prediction of SS. Moreover, we explored associations between SS and clinicopathological features. Furthermore, we assessed independent predictive value of SS by multivariate Cox analysis and then built prognostic models based on clinical stage and SS. Finally, we performed pathway enrichments analysis and investigated immune checkpoints expression underlying SS in four datasets. RESULTS: We established a 13 gene-based SS, which could precisely predict OS and PFS of LUAD. Close relations were elicited between SS and canonical malignant indictors. Furthermore, SS could serve as an independent risk factor for OS and PFS. Besides, the predictive efficacies of prognostic models were also reasonable (C-indexes: OS, 0.7; PFS, 0.7). Finally, we demonstrated enhanced cell proliferation and immune escape might account for high clinical risk of SS. CONCLUSIONS: We built a 13 gene-based SS for prognostic prediction of LUAD, which exhibited wide applicability and could contribute to LUAD management.

TCF19 promotes cell proliferation and tumor formation in lung cancer by activating the Raf/MEK/ERK signaling pathway.

OBJECTIVE: This study aimed to investigate TCF19's role in lung cancer development, specifically its involvement in the RAF/MEK/ERK signaling pathway. METHODS: Lung cancer tissue analysis revealed significant TCF19 overexpression. In vitro experiments using A549 and Hop62 cells with TCF19 overexpression demonstrated enhanced cell growth. Transgenic mouse models confirmed TCF19's role in primary tumor development. Transcriptome sequencing identified altered gene expression profiles, linking TCF19 to RAF/MEK/ERK pathway activation. Functional assays elucidated underlying mechanisms, revealing increased phosphorylation of Raf1, MEK1/2, and ERK1/2. Inhibiting RAF1 or ERK through shRaf1 or ERK inhibitor reduced cell cycle-related proteins and inhibited TCF19-overexpressing cell growth. RESULTS: TCF19 was identified as an oncogene in lung carcinoma, specifically impacting the RAF/MEK/ERK pathway. Elevated TCF19 levels in lung cancer suggest targeting TCF19 or its associated pathways as a promising strategy for disease management. CONCLUSION: This study unveils TCF19's oncogenic role in lung cancer, emphasizing its modulation of the RAF/MEK/ERK pathway and presenting a potential therapeutic target for TCF19-overexpressing lung cancers.

Effects of postoperative adjuvant radiotherapy on stage IIIA-N2 non-small cell lung cancer and prognostic analysis.

PURPOSE: We aimed to explore the efficacy and safety of postoperative adjuvant radiotherapy in the treatment of non-small cell lung cancer (NSCLC) (stage IIIA-N2), and to analyze the influencing factors for the prognosis of patients. METHODS: A total of 142 patients with NSCLC (stage IIIA-N2) were collected for retrospective analysis. Postoperative adjuvant radiotherapy was performed in 71 cases (Radiotherapy group), while it was not conducted in the remaining 71 cases (Control group). The survival status of patients was recorded during follow-up. Moreover, the possible influencing factors for the prognosis of patients were analyzed. RESULTS: The median survival time was 34.7±5.4 months and 31.9±4.9 months, the 5-year overall survival (OS) rate was 32.4% and 26.8%, and the 5-year progression-free survival (PFS) rate was 25.4% and 12.7%, respectively, in the Radiotherapy group and the Control group. The 5-year OS was significantly correlated with smoking history, tumor T stage, ratio of positive lymph nodes, number of cycles of postoperative chemotherapy, and whether postoperative adjuvant radiotherapy was combined. Moreover, tumor T stage, ratio of positive lymph nodes and whether adjuvant radiotherapy was combined were independent influencing factors for postoperative OS of patients. The lower tumor T stage, lower ratio of positive lymph nodes and adjuvant radiotherapy combined corresponded to the higher OS rate. CONCLUSIONS: Postoperative adjuvant radiotherapy is safe and feasible in the treatment of NSCLC (stage IIIA-N2), which can increase the survival of patients and the local control rate of tumors. Patients with a lower tumor T stage and a lower ratio of positive lymph nodes have higher survival rates.