Systematically integrative analysis identifies diagnostic and prognostic candidates and small-molecule drugs for lung adenocarcinoma

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer (LC).However, the early-stage diagnostic rate is still low, and the 5-year overall survival (OS) rate remains poor. The present study aimed to identify critical genes as diagnostic and prognostic markers and small-molecule drugs for combating LUAD using a systematic bioinformatics analysis.Methods: Five gene expression profiling datasets were systematically integrated and analyzed. First, gene coexpression modules were identified, and differentially expressed genes (DEGs) were screened. Second, the functional changes of these DEGs were systematically investigated. Third, the protein-protein interaction network, high correlation module and key genes were identified. Fourth, prognosis and diagnostic analyses were performed. Fifth, small-molecule drugs were predicted for guiding LUAD therapy.Results: Finally, 12-gene and 2-gene signatures were identified as diagnostic and prognostic markers.The areas under the curves (AUCs) of two signatures associated with 3-year survival were 0.686 and 0.603, respectively. The AUCs of two signatures were over 95% and 94% in diagnostic model, separately. Eleven small-molecule drugs were found and irinotecan was simultaneously predicted in three drug databases. Conclusions:The present study identified some key dysregulated genes involved in LUAD and potential drugs by a comprehensive analysis, which provides novel insights into the pathological mechanism involved in LUAD and may shed light on the diagnosis, prognosis and treatment of LUAD patients.

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma

“…Developing a robust prognostic signature is very important to effectively predict the survival of LUAD patients. In recent years, many types of molecular prognostic signatures have been developed, including protein, mRNA, miRNA and lncRNA [6][7][8][9][10]. Some signatures have also showed better predictive capability [38,39,42,45].…”

“…However, due to the high heterogeneity of LUAD, the prognoses of LUAD patients within the same TNM group presented heterogeneous outcomes [6], which suggests that some new prognostic methods should be developed and used to refine risk stratification, such as molecular prognostic marker [6]. In recent years, with the progress of molecular biology, some molecular prognostic markers including protein, mRNA, miRNA, lncRNA, and oncogene were identified [6][7][8][9][10]. In addition, liquid biopsies based on circulating tumor cells (CTCs) and circulating free DNA (cfDNA) and tumor microenvironment (TME) based on tumor-infiltrating immune cells (TICs) are of much interest to many scientists in predicting the survival, and some valuable results have been obtained [6,11,12].…”

High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses

“…To date, ANXA3 has been found to not only maintain genomic integrity and facilitate cell proliferation and differentiation but also contributes to tumor initiation and growth. We synthesized the relevant literature and found that that ANXA3 expression was dysregulated in a large number of tumor populations, such as bladder urothelial carcinoma ( 23 ), BRCA ( 17 ), CHOL ( 16 ), COAD ( 24 ), esophageal carcinoma ( 25 ), head and neck squamous cell carcinoma ( 26 ), kidney chromophobe ( 27 ), kidney renal papillary cell carcinoma ( 28 ), hepatocellular carcinoma ( 29 ), LUAD ( 30 ), LUSC ( 31 ), pancreatic adenocarcinoma ( 32 ), PRAD ( 33 ), READ ( 34 ), stomach adenocarcinoma ( 25 ), thyroid carcinoma ( 35 ), and uterine corpus endometrial carcinoma ( 13 ). In this study, an increased ANXA3 expression was associated with a favorable prognosis, suggesting that ANXA3 might play a pivotal role in decreasing cancer risk in patients with OV.…”