title: Overexpression and cytoplasmic accumulation of Hepl is associated with clinicopathological parameters and poor prognosis in non-small cell lung cancer.
abstract: Hepl, first described in 2008, is the fourth member of the Crk-associated substrate (CAS) family and is specifically expressed in the lung. Compared to other CAS proteins, Hepl has a varying effect on cell migration in different cell types. We speculated that Hepl may play a role in lung cancer invasion and metastasis. We quantified the expression and subcellular localization of Hepl in 143 non-small cell lung cancer (NSCLC) tissues, adjacent noncancerous tissues, and eight lung cancer cell lines using Western blotting, immunohistochemistry, and immunofluorescent staining. Expression of Hepl was correlated with the clinicopathological features of NSCLC. Hepl was overexpressed in 72.3 % (103/143) of the NSCLC tissues, compared to the adjacent noncancerous lung tissues (P = 0.022). Overexpression of Hepl was associated with lymph node metastasis and high TNM stage (P = 0.005 and P = 0.045, respectively). Kaplan-Meier survival curves and the log-rank test indicated that overexpression of Hepl correlated with poorer overall survival in NSCLC (P < 0.001), and Cox regression analysis demonstrated that overexpression of Hepl was an independent prognostic factor in NSCLC. Furthermore, cytoplasmic accumulation of Hepl was observed in a high metastatic potential lung cancer cell lines (H1299 and BE1), but not in low metastatic potential cell lines (LTE and A549). This study reveals that Hepl is overexpressed in the nucleus and aberrantly accumulates in the cytoplasm of NSCLC cells, and indicates that Hepl may play a role in the progression of lung cancer, including lymph node metastasis and TNM stage. Additionally, Hepl may be a useful prognostic factor in lung cancer.
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Li
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Liu
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Cao
authors.forename: Xiu-Peng
authors.initials: XP
authors.lastname: Zhang
authors.forename: Gui-Yang
authors.initials: GY
authors.lastname: Jiang
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C533047:CASS4 protein, human