title: Combinations of laminin 5 with PTEN, p-EGFR and p-Akt define a group of distinct molecular subsets indicative of poor prognosis in patients with non-small cell lung cancer.
abstract: Laminin 5 (Ln5) is an extracellular matrix protein that plays an important role in cell migration and tumor invasion. This study explored the expression of Ln5 and the role of its relationships with PTEN, phospho-EGFR (p-EGFR) and phospho-Akt (p-Akt) in the prognosis of patients with non-small cell lung cancer (NSCLC). The protein expression of Ln5, PTEN, p-EGFR and p-Akt was assessed by immunohistochemical analysis, and their relationships to prognosis were analyzed. Protein expression of Ln5, p-EGFR and p-Akt was detected in 61.2 (60/98), 60.2 (59/98) and 45.3% (43/95) of patients with NSCLC, respectively. Loss of PTEN expression was found in 67.7% of tumors (65/96). Ln5 expression was related to patient gender, histology and p-Akt expression (χ(2)=3.901, 4.549 and 6.985, respectively; P=0.048, 0.033 and 0.008, respectively). Patients with positive Ln5 expression had marginally poorer survival than Ln5-negative patients (median survival time 56.4 months vs. not reached; χ(2)=3.346; P=0.067). Overall survival was significantly different in patients with positive Ln5 expression combined with loss of PTEN, positive p-EGFR expression or positive p-Akt expression. Cox regression analysis showed that stage, co-expression of Ln5 and p-Akt, and PTEN were the three most independent prognostic factors for patients with NSCLC (χ(2)=27.906; P<0.0005). The results highlight the complex relationships between extracellular matrix proteins and key signaling pathway molecules in tumorigenesis. Changes in the expression of Ln5 plus PTEN, p-EGFR or p-Akt define a distinct subset of lung cancers. Patients with such cancers have poorer survival and require early treatment that impacts survival.
authors.affiliation: Guangdong Lung Cancer Institute, Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080,  P.R. China.
authors.forename: She-Juan
authors.initials: SJ
authors.lastname: An
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.forename: Xu-Chao
authors.initials: XC
authors.lastname: Zhang
authors.forename: Hai-Yu
authors.initials: HY
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Chen
authors.forename: Wei-Bang
authors.initials: WB
authors.lastname: Guo
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu