Abstract
BackgroundTo evaluate the insulin receptor isoform mRNA expression status in non-small cell lung cancer (NSCLC) patients.MethodsRNA-seq data from 614 NSCLC [355 adenocarcinomas (LUAD) and 259 squamous cell carcinomas (LUSC)] and 92 normal lung specimens were obtained from The Cancer Genome Atlas (TCGA) to evaluate the mRNA expression of insulin receptor isoform A (IR-A) and insulin receptor isoform B (IR-B). The differential expression status of the insulin receptor isoforms in NSCLC patients was confirmed using qRT-PCR assays with lung cancer cDNA arrays and primary tumor samples.ResultsThe mRNA expression levels of IR-B were significantly lower in some NSCLC samples compared to normal lung specimens, including both LUAD and LUSC. Notably, no IR-B transcripts were detected - only the IR-A isoform was expressed in 11% of NSCLC patients. This decrease in IR-B expression contributed to an elevated IR-A/IR-B ratio, which was also associated with lower epithelial-mesenchymal transition gene signatures in NSCLC and longer patient survival under standard of care in LUSC. In addition to NSCLC, RNA-seq data from TCGA revealed a similar increase in IR-A/IR-B ratio in many other cancer types, with high prevalence in acute myeloid leukemia, glioblastoma multiforme, and brain lower grade glioma.ConclusionsOur results indicate a common reduction of the mRNA expression level of IR-B and an increased IR-A/IR-B mRNA ratio in NSCLC and other tumor types. The relationship of altered IR-A/IR-B ratios with cancer progression and patient survival should be prospectively explored in future studies.
Highlights
To evaluate the insulin receptor isoform mRNA expression status in non-small cell lung cancer (NSCLC) patients
Our results suggest that the isoform A (IR-A)/ isoform B (IR-B) mRNA ratio may serve as a prognostic maker to guide clinical treatment decisions of Lung squamous cell carcinoma (LUSC); and characterizing the specific relationship of this biomarker with prognosis and treatment response might be valuable for other cancer indications
Higher IR-A/IR-B mRNA ratio is observed in NSCLC patients using a large patient population from The Cancer Genome Atlas (TCGA) To evaluate the expression of IR-A and IR-B mRNAs in NSCLC, we utilized the large RNA-seq database from TCGA
Summary
To evaluate the insulin receptor isoform mRNA expression status in non-small cell lung cancer (NSCLC) patients. Insulin is a crucial growth factor that binds to the insulin receptor (INSR) and subsequently activates the PI3K-AKT pathway. This pathway is mainly responsible for mediating the metabolic effects of insulin and regulating the MAP kinase pathway that influences important biological processes, such as cell growth and differentiation [3]. The relative level of mRNA encoding IR-A and IR-B is regulated in a tissue-specific manner [4,5], and depends on the stage of cell development and differentiation. In fetal tissues and cancerous cells, IR-A is the predominant isoform [5]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
