title: Increased IR-A/IR-B ratio in non-small cell lung cancers associates with lower epithelial-mesenchymal transition signature and longer survival in squamous cell lung carcinoma.
abstract: BACKGROUND
  To evaluate the insulin receptor isoform mRNA expression status in non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  RNA-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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors.forename: Liyan
authors.initials: L
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Katie
authors.initials: K
authors.lastname: Streicher
authors.forename: Chris
authors.initials: C
authors.lastname: Morehouse
authors.forename: Philip
authors.initials: P
authors.lastname: Brohawn
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Ge
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Dong
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yin
authors.forename: Guanshan
authors.initials: G
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.forename: Koustubh
authors.initials: K
authors.lastname: Ranade
authors.forename: Brandon W
authors.initials: BW
authors.lastname: Higgs
authors.affiliation: MedImmune Inc,, LLC, One MedImmune Way, 20878 Gaithersburg, MD, USA. yaoy@medimmune.com.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yao
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Huang
mesh_terms: D017398:Alternative Splicing; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D059368:RNA Isoforms; D012333:RNA, Messenger / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics*
chemical_list: D059368:RNA Isoforms; D012333:RNA, Messenger; D011972:Receptor, Insulin