Identification of mutant genes with high‐frequency, high‐risk, and high‐expression in lung adenocarcinoma

Abstract

Background: To identify mutant genes with high-frequency-risk-expression between lung adenocarcinoma and normal samples. Methods:The ribonucleic acid RNA-Seq data GSE34914 and GSE37765 were downloaded from the Gene Expression Omnibus database, including 12 lung adenocarcinoma samples and six controls. All RNA-Seq reads were processed and the geneexpression level was calculated. Single nucleotide variation (SNV) was analyzed and the locations of mutant sites were recorded. In addition, the frequency and risk-level of mutant genes were calculated. Gene Ontology (GO) functional analysis was performed. The reported cancer genes were searched in tumor suppressor genes, Cancer Genes, and the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Results: The SNV annotations of somatic mutation sites showed that 70% of mutation sites in the exon region occurred in the coding sequence (CDS). Thyroid hormone receptor interactor (TRIP)12 was identified with the highest frequency. A total of 118 mutant genes with high frequency and high-risk were selected and significantly enriched into several GO terms. No base mutation of cyclin C (CCNC) or RAB11A was recorded. At fragments per kilobase per million reads (FPKM) ≥ 56.5, reported tumor suppressor genes catenin (cadherin-associated protein), delta (CTNND)1, dual specificity phosphatase (DUSP)6, malate dehydrogenase (MDH)1 and RNA binding motif protein (RBM)5, were identified. Notably, signal transducer and activator of transcription 2 (STAT2) was the only transcription factor (TF) with high-risk mutation and its expression was detected. Conclusion: For the mutant genes with high-frequency-risk-expression, CTNND1, DUSP6, MDH1 and RBM5 were identified. TRIP12 might be a potential cancer-related gene, and expression of TF STAT2 with high-risk was detected. These mutant gene candidates might promote the development of lung adenocarcinoma and provide new diagnostic potential targets for treatment.

Characterization of the Role of the Malate Dehydrogenases to Lung Tumor Cell Survival

“…MDH1 has also been shown to be highly expressed in muscle metastases from pancreatic adenocarcinomas 18 . While mutations in the MDH1 have been reported in lung cancer, it is not known if these mutations affect its enzymatic activity 19 .…”

Dysregulation of miR-605-5p/STAT2 axis predicts an unfavorable survival in patients with gastric cancer

“…The upregulation of STAT2 has been reported associated with a poor prognosis in cancers. 3,4 We found that high expression of STAT2 was associated with a poor survival and acted as an independent prognostic factor of poor survival in GC patients. Furthermore, the upregulation of STAT2 was attributable to the post-transcriptional modulation rather than its genetic and epigenetic alterations in GC.…”

Cancer gene mutations in congenital pulmonary airway malformation patients

“…Following the cancer angle, the inhibitor of growth gene ING , involved in head and neck squamous cell carcinoma, is also de novo mutated. Although not reported in the current databases, an exhaustive literature search described TRIP12 as a potential lung adenocarcinoma gene [19]. CEP295 , a key gene in centriole formation, has a loss-of-function variant.…”