Bcl-2 and β1-integrin predict survival in a tissue microarray of small cell lung cancer

Abstract

Introduction:Survival in small cell lung cancer (SCLC) is limited by the development of chemoresistance. Factors associated with chemoresistance in vitro have been difficult to validate in vivo. Both Bcl-2 and β1-integrin have been identified as in vitro chemoresistance factors in SCLC but their importance in patients remains uncertain. Tissue microarrays (TMAs) are useful to validate biomarkers but no large TMA exists for SCLC. We designed an SCLC TMA to study potential biomarkers of prognosis and then used it to clarify the role of both Bcl-2 and β1-integrin in SCLC.Methods:A TMA was constructed consisting of 184 cases of SCLC and stained for expression of Bcl-2 and β1-integrin. The slides were scored and the role of the proteins in survival was determined using Cox regression analysis. A meta-analysis of the role of Bcl-2 expression in SCLC prognosis was performed based on published results.Results:Both proteins were expressed at high levels in the SCLC cases. For Bcl-2 (n=140), the hazard ratio for death if the staining was weak in intensity was 0.55 (0.33–0.94, P=0.03) and for β1-integrin (n=151) was 0.60 (0.39–0.92, P=0.02). The meta-analysis showed an overall hazard ratio for low expression of Bcl-2 of 0.91(0.74–1.09).Conclusions:Both Bcl-2 and β1-integrin are independent prognostic factors in SCLC in this cohort although further validation is required to confirm their importance. A TMA of SCLC cases is feasible but challenging and an important tool for biomarker validation.

Characterization of human dental pulp cells-derived spheroids in serum-free medium: Stem cells in the core

“…N‐cadherin (CDH2) (also a neural marker) has been demonstrated involving in intercellular adhesion‐dependent cell survival [Peluso et al, ; Lelièvre et al, ]. Integrin‐β1 (ITGB1) signaling pathway not only provides an adhesive interaction but also regulates cell growth and prevents apoptosis [Gary and Mattson, ; Bouchard et al, ; Lawson et al, ]. Our data showed that FGF3 and FGF4 were expressed at both central and intermediate zone as same as the stem cells markers STRO‐1 and CD146, and the expression of CDH2 and ITGB1 was increased in a time‐dependent manner in spheroids suggesting FGF signaling and intercellular adhesion molecules likely played roles in stem cell survival.…”

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

“…According to Kononen and colleagues [29] tissue microarrays (TMAs) were developed to allow high throughput analysis of protein expression in tumors tissues and many authors agree that they can be used to validate biomarkers [30-32]. Here, β1 integrin expression and its relationship with survival of patients with IDC were analyzed in a tissue microarray.…”

Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1

“…Despite the lack of kinase activities, integrins can form a cluster and allow the intracellular domain of their β subunit to recruit and activate kinases, such as focal adhesion kinases (FAKs), SRC family kinases (SFKs), and other signaling proteins, which then elicit specific intracellular signaling events in response to various environmental stimuli (22). In SCLC, integrin β1 is the predominant integrin β subunit and known as a potential marker of poor prognosis (17,18,(23)(24)(25). Functionally, integrin β1 may facilitate SCLC development via promotion of cell migration and invasion through the formation of various α2β1, α3β1, α6β1, and αvβ1 integrins (26,27).…”