Author of

• 30780

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  P2.03 - Biology (ID 162)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30837

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    P2.03-55 - High Integrin α3 Expression Is Associated with Poor Prognosis in Patients with NSCLC (ID 2543)

    10:15 - 18:15  |  Author(s): Tao Wang
    • Abstract

    Background
    

    Integrin α3β1 belongs to a family of heterodimeric transmembrane glycoprotein receptors that mediates cell adhesion and cytoskeleton function. We recently showed that integrin α3β1 is a promising novel cancer biomarker and drug target in NSCLC. While the integrin α3 unit (INTA3) mediates the binding to various ligands and substrates, the integrin β1 unit (INTB1) mainly is primarily responsible for the complex biological functions. INTA3 only binds to INTB1 as the binding partner. This study was undertaken to evaluate if INTA3 expression was correlated with clinicopathological parameters and survival in patients with non-small cell lung cancer (NSCLC).

    Method
    

    Tissue microarrays (TMAs) were made from archival formalin-fixed and paraffin-embedded tissue blocks of 161 NSCLC patients, which included 91 adenocarcinoma (LUAD), 46 squamous carcinomas (LUSC), and 24 other histology types. TMA sections were stained for INTA3 expression using anti-integrin α3 antibody (ab131055, dilution 1:100; Abcam) by immunohistochemistry (IHC) stain. Staining intensity was graded as 0 (0-5%, negative), 1+ (6-20%, weak), 2+ (21-50%, moderate), and 3+ (51-100%, strong). Kaplan-Meier curves and log-rank test were used to compare overall survival of IHC score groups. To adjust for covariate imbalance between IHC score groups, propensity-score-weighted Kaplan-Meier curves and weighted Cox models were used. Logistic regression was used to study association between INTA3 expression and patient clinicopathological parameters.

    Result
    

    INTA3 IHC expression was detected in 107/161 (66.5%) of the NSCLC samples. Weak (1+), moderate (2+) and strong (3+) INTA3 expression was detected in 66 (41.0%), 33 (20.5%), and 8 (5.0%) cases, respectively. Kaplan-Meier curves indicated that weak (1+) and strong (3+) INTA3 expression was significantly associated with poor overall survival in NSCLC patients (p < 0.05 and p < 0.001, respectively). Propensity-score-weighted survival analysis demonstrated that INTA3 IHC expression (1+-3+) was associated with poor prognosis (HR = 1.39, 95% CI: 1.06-1.83, p =0.02) for all NSCLC patients, as well as in subgroups of female patients (HR =1.99, 95% CI: 1.32-3.01, p < 0.01), smokers (HR =2.46, 95% CI: 1.66-3.65 p < 0.01) and differentiation grade I&II (HR =3.0, 95% CI: 1.91-4.59 p < 0.01), but not in LUSC patients (p=0.11), LUAD patients (p=0.07), male patients (p=0.06), non-smokers (p=0.34), differentiation grade III (p=0.98). Logistic regression indicated that high INTA3 expression is associated with no smoke history (OR=2.7, 95% CI:1.3-5.7, p=0.01).

    Conclusion
    

    INTA3 was expressed in the majority of NSCLC by IHC and was associated with poor prognosis. Further study is warranted for targeting integrin α3(β1) in NSCLC.