Oncotarget

Research Papers:

Cav3.1 overexpression is associated with negative characteristics and prognosis in non-small cell lung cancer

Aleksi Suo _, Allison Childers, Adrijana D’Silva, Lars F. Petersen, Shannon Otsuka, Michelle Dean, Haocheng Li, Emeka K. Enwere, Brant Pohorelic, Alexander Klimowicz, Ivana A. Souza, Jawed Hamid, Gerald W. Zamponi, DGwyn Bebb

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Oncotarget. 2018; 9:8573-8583. https://doi.org/10.18632/oncotarget.24194

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Abstract

Aleksi Suo1, Allison Childers2, Adrijana D’Silva1, Lars F. Petersen2, Shannon Otsuka1, Michelle Dean2,3, Haocheng Li1,4, Emeka K. Enwere2,3, Brant Pohorelic3, Alexander Klimowicz3, Ivana A. Souza5, Jawed Hamid5, Gerald W. Zamponi5 and DGwyn Bebb1,2

1Department of Oncology, Tom Baker Cancer Centre, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

2Translational Laboratories, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada

3Functional Tissue Imaging Unit, Translational Laboratory, Tom Baker Cancer Centre, Calgary, AB, Canada

4Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada

5Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

Correspondence to:

Aleksi Suo, email: aleksi.suo@albertahealthservices.ca

Keywords: T-type VGCC; Cav3.1; NSCLC

Received: April 04, 2017     Accepted: December 05, 2017     Published: January 12, 2018

ABSTRACT

Introduction: Voltage-gated calcium channels (VGCC) have been found to be differentially expressed in several different tumor types, but their role in tumor growth, malignant invasion, metastases and impact on clinical outcomes has not been clarified.

Materials and Methods: From a cohort database of 193 patients with early-stage NSCLC, 163 formalin-fixed paraffin-embedded specimens were available for analysis to construct tissue microarrays. Cav3.1 protein expression was detected using fluorescence immunohistochemistry, and quantified using automated image acquisition and analysis.

Results: Among the cohort of 193 NSCLC patients, adenocarcinoma (53.9%) and squamous cell carcinoma (SCC) (30.1%) were the most common histologies. There was no difference between SCC and non-SCC subtypes in overall survival (OS) or relapse-free survival (RFS); 74.2 vs 90.1 months (p = 0.543) and 48.8 vs 52.6 months (p = 0.766), respectively. T-type VGCC 3.1 (Cav3.1) overexpression was assessed by tissue microarray immunohistochemistry analysis from 163 available patient samples. Eighteen (11.0%) NSCLC primaries were found to have Cav3.1 overexpression levels, and were significantly associated with SCC histology (p < 0.001), larger tumor size (p < 0.001) and later stage disease at diagnosis (p = 0.019). Median OS was 48.6 vs 106.7 months for Cav3.1 overexpressing and non-overexpressing patients, respectively (p = 0.032). Regression analysis revealed a significantly negative effect for Cav3.1 overexpression on RFS (Hazard ratio [HR] = 2.02, p = 0.048).

Conclusions: Cav3.1 overexpression is a potential biomarker for poorer patient outcomes. These results bring supportive evidence for calcium channels inducing an aggressive phenotype in NSCLC and potentially may serve as a therapeutic target in overexpressing tumors.


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