Abstract
Alternative splicing (AS), an essential process for the maturation of mRNAs, is involved in tumorigenesis and tumor progression, including angiogenesis, apoptosis, and metastasis. AS changes can be frequently observed in different tumors, especially in geriatric lung adenocarcinoma (GLAD). Previous studies have reported an association between AS events and tumorigenesis but have lacked a systematic analysis of its underlying mechanisms. In the present study, we obtained splicing event information from SpliceSeq and clinical information regarding GLAD from The Cancer Genome Atlas. Survival-associated AS events were selected to construct eight prognostic index (PI) models. We also constructed a correlation network between splicing factors (SFs) and survival-related AS events to identify a potential molecular mechanism involved in regulating AS-related events in GLAD. Our study findings confirm that AS has a strong prognostic value for GLAD and sheds light on the clinical significance of targeting SFs in the treatment of GLAD.
Highlights
Cancer morbidity and mortality rates are rapidly increasing worldwide
Cancer-related Alternative splicing (AS) events were selected in 59 normal controls and 513 tumor tissues from the The Cancer Genome Atlas (TCGA) SpliceSeq database
Splicing of pre-mRNA is essential for the maturation of mRNAs, and it is an important step in regulating the expression of protein and genes
Summary
Lung cancer is the most common cause of cancer-related mortality [1]. Adenocarcinoma is the most common type, accounting for approximately 60% of NSCLCs [3]. A study analyzing the genetic characteristics of 184 patients with lung adenocarcinoma showed that distinctive genetic profile including the Kristen rat sarcoma viral oncogene, serine/threonine kinase 11 (STK11), and epidermal growth factor receptor (EGFR) exon 20 mutation were common in the older patient group. Tumor biomarkers, tumor stages, and molecular markers are common indicators that predict the prognosis of patients with lung adenocarcinoma (LUAD) [5,6,7]. The number of biomarkers that can be used clinically is limited and no prognostic model was built exclusively for elderly patients. Novel and effective prediction methods are needed to predict the prognosis of GLAD
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