CACNA1B (Cav2.2) Overexpression and Its Association with Clinicopathologic Characteristics and Unfavorable Prognosis in Non-Small Cell Lung Cancer

Abstract

CACNA1B (Ca_v2.2) encodes an N-type voltage-gated calcium channel (VGCC) ubiquitously expressed in brain and peripheral nervous system that is important for regulating neuropathic pain. Because intracellular calcium concentration is a key player in cell proliferation and apoptosis, VGCCs are implicated in tumorigenesis. Recent studies have identified CACNA1B (Ca_v2.2) being overexpressed in prostate and breast cancer tissues when compared to adjacent normal tissues; however, its role in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we determined the mRNA and protein expression of CACNA1B (Ca_v2.2) in NSCLC tumorous and adjacent nontumorous tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC), respectively. CACNA1B (Ca_v2.2) protein expressions in tumorous tissues were correlated with NSCLC patients' clinical characteristics and overall survival. CACNA1B (Ca_v2.2) mRNA and protein expression levels were higher in NSCLC tumorous tissues than in nontumorous tissues. High CACNA1B (Ca_v2.2) protein expression was associated with higher TNM stages, and CACNA1B (Ca_v2.2) protein expression is an independent prognostic marker in NSCLC. Based on our results, we conclude that CACNA1B (Ca_v2.2) plays a role in NSCLC development and progression. Elucidating the underlying mechanism may help design novel treatment by specifically targeting the calcium regulation pathway for NSCLC, a devastating disease with increasing incidence and mortality in China.

Figure 1

CACNA1B (Ca_v2.2) mRNA level was significantly higher in NSCLC tumorous tissues than in adjacent nontumorous tissues. CACNA1B (Ca_v2.2) mRNA was determined by qRT-PCR and relative quantification analysis by normalizing to GAPDH mRNA.

Figure 2

Representative immunohistochemistry (IHC) images showing expression of CACNA1B (Ca_v2.22) in tissue microarray sections of NSCLC. (a1) and (a2) show strong positive staining in the cytoplasm of squamous cell carcinoma tissues. (b1) and (b2) show moderate positive staining in the cytoplasm of adenocarcinoma tissues. (c1) and (c2) show a negative IHC reaction in matched adjacent normal tissues. Original magnification was ×40 for (a1) and (b1) and ×400 for (a2) and (b2).

Figure 3

Survival curves of NSCLC patients by the Kaplan–Meier method and the log-rank test. (a) NSCLC patients with high CACNA1B (Ca_v2.2) expression (green line, 1) had significantly worse overall survival than NSCLC patients with low or no CACNA1B (Ca_v2.2) expression (blue line, 0); (b) NSCLC patients with larger tumor (3 cm) (green line, 1) had significantly worse overall survival than NSCLC patients with smaller tumor (<3 cm) (blue line, 0).