Construction of a Prognostic Immune Signature for Squamous-Cell Lung Cancer to Predict Survival.

Background: Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods: We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results: A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion: Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.

Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway.

BACKGROUND: During tumor formation and expansion, increasing glucose metabolism is necessary for unrestricted growth of tumor cells. Expression of key glycolytic enzyme alpha-enolase (ENO1) is controversial and its modulatory mechanisms are still unclear in non-small cell lung cancer (NSCLC). METHODS: The expression of ENO1 was examined in NSCLC and non-cancerous lung tissues, NSCLC cell lines, and immortalized human bronchial epithelial cell (HBE) by quantitative real-time reverse transcription PCR (qRT-PCR), immunohistochemistry, and Western blot, respectively. The effects and modulatory mechanisms of ENO1 on cell glycolysis, growth, migration, invasion, and in vivo tumorigenesis and metastasis in nude mice were also analyzed. RESULTS: ENO1 expression was increased in NSCLC tissues in comparison to non-cancerous lung tissues. Similarly, NSCLC cell lines A549 and SPCA-1 also express higher ENO1 than HBE cell line in both mRNA and protein levels. Overexpressed ENO1 significantly elevated NSCLC cell glycolysis, proliferation, clone formation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo by regulating the expression of glycolysis, cell cycle, and epithelial-mesenchymal transition (EMT)-associated genes. Conversely, ENO1 knockdown reversed these effects. More importantly, our further study revealed that stably upregulated ENO1 activated FAK/PI3K/AKT and its downstream signals to regulate the glycolysis, cell cycle, and EMT-associated genes. CONCLUSION: This study showed that ENO1 is responsible for NSCLC proliferation and metastasis; thus, ENO1 might serve as a potential molecular therapeutic target for NSCLC treatment.