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CENPA regulates tumor stemness in lung adenocarcinoma.

ABSTRACT: Lung adenocarcinoma is a malignant and fatal respiratory disease. However, due to its complex pathogenesis and poorly effective therapeutic options, accurate early diagnosis and prognosis remain elusive. Now, there is increasing evidence that tumor stem cells are involved in tumorigenesis, metastasis, relapse, resistance to chemotherapy and radiotherapy and are one of the reasons why tumors cannot be cured. The mRNA expression based-stemness index (mRNAsi) is a parameter obtained by Malta and his colleagues applying innovative one-class logistic regression machine learning algorithm (OCLR) on mRNA expression in normal stem cells and their progeny. It is a valid evaluation parameter and is currently employed to evaluate the degree of differentiation of a certain tumor. In this study, we first used WGCNA and the software Cytoscape to obtain key modules and hub genes. We then applied LASSO regression analysis to calculate the genes in the key module to obtain a six-gene risk model. Moreover, the accuracy of this model was validated. Finally, we took the intersection of hub genes and risk genes and validated CENPA as both a tumor stemness regulator and a tumor prognostic factor in lung cancer.

SUBMITTER: Yu QY

PROVIDER: S-EPMC9320546 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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CENPA regulates tumor stemness in lung adenocarcinoma.

Yu Qi-Ying QY Liu Hui H Liu Chen C Xiang Yuan Y Zong Qi-Bei QB Wang Jun J Zhang Hui-Min HM Xu Cheng-Chen CC Li Jia-Peng JP Liao Xing-Hua XH

Aging 20220711 13

Lung adenocarcinoma is a malignant and fatal respiratory disease. However, due to its complex pathogenesis and poorly effective therapeutic options, accurate early diagnosis and prognosis remain elusive. Now, there is increasing evidence that tumor stem cells are involved in tumorigenesis, metastasis, relapse, resistance to chemotherapy and radiotherapy and are one of the reasons why tumors cannot be cured. The mRNA expression based-stemness index (mRNAsi) is a parameter obtained by Malta and hi ...[more]

PMID: 35816352

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Project description:BackgroundLung cancer is the second common cancer type in western countries and has a high mortality. During the development and progression of the tumor, the nutrients in its environment play a central role. The tumor cells depend crucially on glucose metabolism and uptake. Tumor cell metabolism is dominated by the Warburg effect, where tumor cells produce large amounts of lactate from pyruvate under aerobic conditions. We thus reasoned that, reducing carbohydrates in the diet might support anti-tumoral effects of current immunotherapy and additionally target tumor immune escape.ObjectivesThe link between reducing carbohydrates to improve current immunotherapy is not clear. We thus aimed at analyzing the effects of different glucose levels on the tumor development, progression and the anti-tumoral immune response.MethodsWe correlated the clinical parameters of our LUAD cohort with different metabolic markers. Additionally, we performed cell culture experiments with A549 tumor cell line under different glucose levels. Lastly, we investigated the effect of low and high carbohydrate diet in an experimental murine model of lung cancer on the tumor progression and different immune subsets.ResultsHere we found a positive correlation between the body mass index (BMI), blood glucose levels, reduced overall survival (OS) and the expression of Insulin-like growth factor-1 receptor (IGF1R) in the lung tumoral region of patients with lung adenocarcinoma (LUAD). Furthermore, increasing extracellular glucose induced IGF1R expression in A549 LUAD cells. Functional studies in a murine model of LUAD demonstrated that, glucose restricted diet resulted in decreased tumor load in vivo. This finding was associated with increased presence of lung infiltrating cytotoxic CD8+ T effector memory (TEM), tissue resident memory T (TRM) and natural killer cells as well as reduced IGFR mRNA expression, suggesting that glucose restriction regulates lung immunity in the tumor microenvironment.ConclusionsThese results indicate that, glucose restricted diet improves lung immune responses of the host and suppresses tumor growth in experimental lung adenocarcinoma. As glucose levels in LUAD patients were negatively correlated to postoperative survival rates, glucose-restricted diet emerges as therapeutic avenue for patients with LUAD.

Dataset Information

CENPA regulates tumor stemness in lung adenocarcinoma.

Publications

CENPA regulates tumor stemness in lung adenocarcinoma.

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