Integrin expression profiling identifies integrin alpha5 and beta1 as prognostic factors in early stage non-small cell lung cancer

Abstract

Background: Selection of early stage non-small cell lung cancer patients with a high risk of recurrence is warranted in order to select patients who will benefit from adjuvant treatment strategies. We evaluated the prognostic value of integrin expression profiles in a retrospective study on frozen primary tumors of 68 patients with early stage non-small cell lung cancer.

Methods: A retrospective study was performed on frozen primary tumors of 68 early stage non-small cell lung cancer patients with a follow up of at least 10 years. From all tumor tissues, RNA was isolated and reverse transcribed into cDNA. qPCR was used to generate mRNA expression profiles including integrins alpha1, 2, 3, 4, 5, 6, 7, 11, and V as well as integrins beta1, 3, 4, 5, 6, and 8.

Results: The expression levels of integrins alpha5, beta1 and beta3 predicted overall survival and disease free survival in early stage NSCLC patients. There was no association between integrin expression and lymph node metastases. Comparison between the histological subtypes revealed a distinct integrin signature for squamous cell carcinoma while the profiles of adenocarcinoma and large cell carcinoma were largely the same.

Conclusion: Integrin expression in NSCLC is important for the development and behavior of the tumor and influences the survival of the patient. Determining the integrin expression profile might serve as a tool in predicting the prognosis of individual patients.

Figure 1

Integrin expression profile in NSCLC. A) Agarose gel electrophoresis of the specific integrin fragments. M = 100 bp DNA marker. B) Representative dilution curves of 4 integrins showing a broad linear range of detection. Ct = Cycle threshold. C) Box plot of the overall integrin expression profile in NSCLC tissues.

Figure 2

Integrin expression profile and overall survival in NSCLC. Kaplan Meier plot of overall survival (OS) of patients with detectable or undetectable integrin beta3 expression and of patients with low (below median) or high (above median) expression of the indicated integrins.

Figure 3

Integrin expression and disease free survival in NSCLC. Kaplan Meier plots of disease free survival (DFS) of patients with detectable or undetectable integrin beta3 expression and of patients with low (below median) or high (above median) expression of the indicated integrins.

Figure 4

Integrin expression profile and survival in subtypes of NSCLC. A) Bar graph showing the subtype specific integrin expression. B) Scatter plot showing the correlation in integrin expression between the different subtypes of NSCLC. C) Kaplan Meier plots of overall survival of patients with low (below median) or high (above median) expression of the indicated integrins in squamous carcinoma.