1. A functional SNP in MRPL43 modulates lung cancer susceptibility and survival through alternative splicing of its isoforms
- Author
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Ana I. Robles, Andrew C. McClary, Yun Yokota, Jessica Roberts, Bríd M. Ryan, Dominic Esposito, Kara Calhoun, Hirokazu Okayama, Rama Modali, Kouya Shiraishi, Majda Haznadar, Takashi Kohno, Elise Eowman, Cassidy Alexandre, and Mohammed Safwan Ali Khan
- Subjects
Gene isoform ,Pulmonary and Respiratory Medicine ,business.industry ,Alternative splicing ,Gene signature ,Bioinformatics ,Lung cancer susceptibility ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Gene expression ,Medicine ,SNP ,030212 general & internal medicine ,Signal transduction ,business ,Gene - Abstract
two cohorts by incorporating the resulting coefficients of multivariable Cox regression model into a score that utilizes linear gene expression values. This gene expression classifier was validated in 6 additional publicly available datasets of stage I/II lung SCC (N 1⁄4 358). The classifier identified high-risk patients in multiple large-scale and geographically diverse cohorts (N 1⁄4 570). The results appear to be independent of race and gene expression platform. Canonical pathways associated with this signature encompass proteins involved in signal transduction, tissue remodeling, and cell motility that would broadly lead to cancer cell migration, invasion and proliferation, suggesting that the gene signature identifies molecular subsets of patients with clinical relevance. This gene classifier could be used to guide clinical decisions after surgical resection. Thus, we would advocate that this classifier be incorporated into prospective trials for further evaluation of its clinical effectiveness.
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