High integrin a3 expression is associated with poor prognosis in patients with non-small cell lung cancer

Qianping Li, Weijie Ma, Shuai Chen, Eddie C. Tian, Sixi Wei, Reggie R. Fan, Tao Wang, Chihong Zhou, Tianhong Li

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We previously showed that a3ß1 integrin is a novel cancer biomarker and drug target in nonsmall cell lung cancer (NSCLC). This study characterized the integrin a3 (ITGA3) expression on patient specimens. Methods: Tissue microarrays (TMAs) were prepared from archival tissue blocks containing 161 patients, which included 91 adenocarcinoma (LUAD), 46 squamous carcinomas (LUSC), and 24 other histology types. TMA sections were stained and scored for ITGA3 expression by immunohistochemistry (IHC). Kaplan- Meier curves and log-rank tests were used to compare overall survival (OS) between IHC score groups. Propensity-score-weighted Kaplan-Meier curves and weighted Cox models were used to adjust for covariate imbalance between IHC score groups. Logistic regression was used to determine ITGA3 transcriptome expression in NSCLC in The Cancer Genome Atlas (TCGA). Results: ITGA3 IHC expression (1+ to 3+) was detected in 107/161 (66.5%) of the NSCLC samples, and was associated with poor prognosis at the edge of significance (HR =1.30, 95% CI: 0.99-1.71, P=0.056), but significant (P<0.05) in subgroups of female patients, smokers and tumors with grade I and II differentiation using propensity-score-weighted survival analysis after adjusting for confounders. Multivariate survival analysis based on multiple imputation for missing variables showed ITGA3 expression, old age and metastasis were associated with poor prognosis (P<0.05). ITGA3 IHC expression was associated with poor prognosis in LUSC (HR =2.27, P<0.05) but not in LUAD (HR =1.49, P=0.16). Median ITGA3 expression was significantly higher in LUAD than LUSC (P<0.0001) in the TCGA transcriptome datasets. Using a higher cutoff than LUSC (70.6 vs. 19.5 FPKM), high ITGA3 RNA expression was also associated with poor prognosis in LUAD (P=0.023). ITGA3 interacted with key genes regulating epithelial to mesenchymal transition, angiogenesis, invasion and metastasis in both LUAD and LUSC. Conclusions: High ITGA3 IHC expression was associated with poor prognosis in NSCLC patients. Further study is warranted for targeting a3ß1 integrin in NSCLC.

Original languageEnglish (US)
Pages (from-to)1361-1378
Number of pages18
JournalTranslational Lung Cancer Research
Volume9
Issue number4
DOIs
StatePublished - Aug 2020

Keywords

  • Integrin a3 subunit (ITGA3 subunit)
  • ITGA3
  • Non-small cell lung cancer (NSCLC)
  • Prognosis
  • Tissue microarray (TMA)

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'High integrin a3 expression is associated with poor prognosis in patients with non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this