Prognostic value of Bcl-2 expression in patients with non-small-cell lung cancer: a meta-analysis and systemic review

Abstract

ObjectiveB-cell-lymphoma-2 (Bcl-2) is a proto-oncogene that plays an important role in the regulation of apoptosis and cell survival. However, there are much conflicting data in the literature concerning the association between Bcl-2 and prognosis in non-small-cell lung cancer (NSCLC). There is little in the way of meta-analysis focused on Bcl-2 and its effect on NSCLC prognosis. This study was performed to provide an assessment of whether expression levels of Bcl-2 are associated with prognosis in patients with NSCLC.Materials and methodsWe searched PubMed, the Cochrane Library, and China National Knowledge Infrastructure for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival were evaluated.ResultsFifty published studies including 6,863 patients with lung cancer were included in this meta-analysis. Overall, Bcl-2 was expressed in 33% of the NSCLC tumors studied. Our analysis indicates that NSCLC patients with Bcl-2-positive expression have a better prognosis than those with Bcl-2-negative expression in both Asian and non-Asian study populations (HR 0.79, 95% CI 0.72–0.87, P<0.00001). However, Bcl-2-positive expression seems to have no significant impact on survival of stage I NSCLC patients.ConclusionOur results indicated that Bcl-2 might be a useful prognostic marker for NSCLC generally. Larger clinical trials are needed to confirm the prognostic value of Bcl-2 in stage I NSCLC.

Bcl‐2 family in non‐small cell lung cancer: its prognostic and therapeutic implications

“…Bcl-2 positivity in carcinoma cells turned out an indicator of better OR in all the stage of NSCLC patients (HR ¼ 0.79, 95%CI, 0.72-0.87, P < 0.0001), but no significant correlation was detected between Bcl-2 and survival in stage I NSCLC. 4 The great majority of the study, however, did not detect statistical significance in adenocarcinoma (HR ¼ 0.92, 95% CI, 0.56-1.51, P ¼ 0.73). 4 Prognostic roles of other anti-apoptotic Bcl-2 family proteins Bcl-xL is another well characterized major anti-apoptosis protein, 19 but there are very limit data about the prognostic values of Bcl-xL in lung cancer patients.…”

“…The great majority of the study, however, did not detect statistical significance in adenocarcinoma (HR = 0.92, 95%CI, 0.56–1.51, P = 0.73) …”

“…A recent meta‐analysis also demonstrated that the results are consistent with the previous two studies above. Bcl‐2 positivity in carcinoma cells turned out an indicator of better OR in all the stage of NSCLC patients (HR = 0.79, 95%CI, 0.72–0.87, P < 0.0001), but no significant correlation was detected between Bcl‐2 and survival in stage I NSCLC …”

“…Most anti‐cancer therapeutic agents employed in clinical practice usually induce apoptosis and the status or regulation of the factors involved in the process of apoptosis in carcinoma cells could contribute to the differences in sensitivity or resistance to current anti‐cancer therapies and flaws in apoptotic programs in carcinoma cells could also contribute to the treatment failure of the patients treated. Various apoptotic proteins have been reported to have prognostic and predictive significances with relation to response to cancer therapy . It has recently become evident that subsets of non‐small cell lung cancer (NSCLC) can be further sub classified at the molecular level by the patterns of recurrent 'driver' mutations which could occur in multiple oncogenes, including EGFR, KRAS , ALK, MET .…”

“…Various apoptotic proteins have been reported to have prognostic and predictive significances with relation to response to cancer therapy. [2][3][4] It has recently become evident that subsets of non-small cell lung cancer (NSCLC) can be further sub classified at the molecular level by the patterns of recurrent 'driver' mutations which could occur in multiple oncogenes, including EGFR, KRAS, ALK, MET. 5 These findings regarding the molecular pathogenesis of lung cancer have indeed resulted in the successful application of targeted therapeutic strategies of the patients.…”