Construction and investigation of a combined hypoxia and stemness index lncRNA-associated ceRNA regulatory network in lu
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RESEARCH ARTICLE
Open Access
Construction and investigation of a combined hypoxia and stemness index lncRNA‑associated ceRNA regulatory network in lung adenocarcinoma Lili Guo1, Hongxia Li1, Weiying Li2 and Junfang Tang1*
Abstract Hypoxia and stemness are important factors in tumor progression. We aimed to explore the ncRNA classifier associated with hypoxia and stemness in lung adenocarcinoma (LUAD). We found that the prognosis of LUAD patients with high hypoxia and stemness index was worse than that of patients with low hypoxia and stemness index. RNA expression profiles of these two clusters were analyzed, and 6867 differentially expressed (DE) mRNAs were screened. Functional analysis showed that DE mRNAs were associated with cell cycle and DNA replication.Protein–protein interaction network analysis revealed 20 hub genes, among which CENPF, BUB1, BUB1B, KIF23 and TTK had significant influence on prognosis. In addition, 807 DE lncRNAs and 243 DE miRNAs were identified. CeRNA network analysis indicated that AC079160.1-miR-539-5p-CENPF may be an important regulatory axis that potentially regulates the progression of LUAD. The expression of AC079160.1 and CENPF were positively correlated with hypoxia and stemness index, while miR-539-5p expression level was negatively correlated with hypoxia and stemness index. Overall, we identified CENPF, BUB1, BUB1B, KIF23 and TTK as potentially key genes involved in regulating hypoxia-induced tumor cell stemness, and found that AC079160.1-miR-539-5p-CENPF axis may be involved in regulating hypoxia induced tumor cell stemness in LUAD. Keywords: Lung adenocarcinoma, Hypoxia, Stemness, ceRNA, Differentially expressed gene Introduction Lung cancer is one of the malignant tumors with the highest morbidity and mortality in the world [1]. Lung adenocarcinoma (LUAD) is one of the common pathological types of lung cancer [2]. In recent years, the incidence of LUAD in many countries and regions has exceeded that of squamous cell carcinoma, becoming the most common pathological type of lung cancer [3]. The
*Correspondence: [email protected] 1 Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 1 Beiguandajie, Tongzhou District, Beijing 101149, China Full list of author information is available at the end of the article
5-year survival rate of LUAD is only about 15% [4]. The prognosis of LUAD patients is extremely unsatisfactory [4]. Therefore, the treatment of LUAD must start from the "root". Cancer stem cell theory proposes that in addition to ordinary tumor cells, there are a small number of tumor-propagating cells that can self-renew, continue to proliferate and differentiate [5, 6]. These cells are the seed of a poor prognosis such as tumor recurrence, metastasis and chemotherapy resistance [4, 5]. In recent years, cancer stem cells have been successfully isolated from more and more different types of cancer cells, which provides a solid basis for stem cell theory and makes cancer st
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