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Open Access Highly Accessed Research article

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

Liyan Jiang1, Wei Zhu2, Katie Streicher2, Chris Morehouse2, Philip Brohawn2, Xiaoxiao Ge1, Zhengwei Dong3, Xiaolu Yin3, Guanshan Zhu3, Yi Gu3, Koustubh Ranade2, Brandon W Higgs2, Yihong Yao2* and Jiaqi Huang2*

Author Affiliations

1 Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

2 MedImmune Inc., LLC, One MedImmune Way, 20878 Gaithersburg, MD, USA

3 Innovation Center China, AstraZeneca Global R&D, Shanghai, China

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BMC Cancer 2014, 14:131  doi:10.1186/1471-2407-14-131

Published: 26 February 2014

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.