title: Overexpression of RhoE in Non-small Cell Lung Cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes.
abstract: RhoE, a small G protein, is constitutively GTP bound within the cell and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments. Although emerging evidence suggests that RhoE is causally involved in cancer formation and progression, little is known about its significance in solid cancer, including lung cancer. In the present study, the expression of RhoE was analyzed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), real-time RT-PCR, immunohistochemistry and western blot in 30 patients with Non-small Cell Lung Cancer (NSCLC). Then the correlation of RhoE overexpression with clinical parameters was evaluated. Furthermore, the possible reasons contributing to the RhoE expression were examined by real-time genomic PCR and mutation analysis on DNA sequence and cDNA sequence. Our results revealed that RhoE expression was dramatically increased in lung cancer tissues compared with adjacent nontumoral lung tissues (p <0.01). Immunohistochemistry showed a strong cytoplasmic staining in cancer cells compared with positive membrane staining in adjacent nontumoral proliferative alveolar epitheliums. Moreover, the overexpression of RhoE was significantly associated with the patients' smoking history (p <0.05). 72% tumor tissues displayed DNA copy number changes based on the DNA levels in the matched adjacent nontumoral lung tissues and this copy number changes correlated significantly with RhoE expression and smoking history (p <0.05). Three polymorphisms were identified but no correlation was found with the clinicopathological features. To our knowledge, this is the first report demonstrating that overexpression of RhoE correlated with smoking and DNA copy number changes, suggesting that RhoE may serve as a molecular marker to identify high-risk individuals and assist in the identification of additional pathways of carcinogenesis.
authors.affiliation: Department of Surgery, Cancer Hospital (Institute), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Cuiyan
authors.forename: Hang
authors.initials: H
authors.lastname: Jie
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Kezhi
authors.forename: Wan
authors.initials: W
authors.lastname: Junting
authors.forename: Shi
authors.initials: S
authors.lastname: Susheng
authors.forename: Feng
authors.initials: F
authors.lastname: Xiaoli
authors.forename: Li
authors.initials: L
authors.lastname: Ning
authors.forename: Mu
authors.initials: M
authors.lastname: Xinhua
authors.forename: Chen
authors.initials: C
authors.lastname: Zhaoli
authors.forename: Shao
authors.initials: S
authors.lastname: Kang
authors.forename: Qiu
authors.initials: Q
authors.lastname: Bin
authors.forename: Li
authors.initials: L
authors.lastname: Baozhong
authors.forename: Chang
authors.initials: C
authors.lastname: Sheng
authors.forename: Xiong
authors.initials: X
authors.lastname: Meihua
authors.forename: He
authors.initials: H
authors.lastname: Jie
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics*; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C508705:RND3 protein, human; D020741:rho GTP-Binding Proteins