title: Prediction of survival prognosis of non-small cell lung cancer by APE1 through regulation of Epithelial-Mesenchymal Transition.
abstract: The DNA base excision repair gene APE1 involves in DNA damage repair pathway and overexpression in a variety of human cancers. Analyses of patients with non-small cell lung cancer (NSCLC) suggested that multiple factors associated with prognosis of NSCLC patients. Further investigation showed that APE1 expression was able to predict the progression-free survival and overall survival in patients with NSCLC and correlated with lymph node metastasis. Intriguingly, as a stratification of APE1-141 SNPs in APE1 positive expression, we also found APE1-141 GT/GG was identified as a marker for prediction of poor survival in NSCLC patients. In the in vitro experiments, the results showed that when APE1 expression was inhibited by siRNA or AT101 (an APE1 inhibitor), the migration and invasion of NSCLC cells were suppressed. Furthermore, Epithelial-Mesenchymal Transition (EMT) markers was tested to provide evidence that APE1 promoted NSCLC EMT through interaction with SirT1. Using NSCLC xenograft models, we confirmed that AT101 shrank tumor volumes and inhibited lymph node metastasis. In conclusion, APE1 could be a potential target for patients with NSCLC metastasis and AT101 is a potent inhibitor in further treatment of NSCLC patients.
authors.affiliation: Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wei
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Senior Ward, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Chongbiao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: The Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Luo
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xin
authors.affiliation: Department of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006072:Gossypol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D006072:Gossypol; C028178:gossypol acetic acid
keywords: APE1; Epithelial-Mesenchymal Transition (EMT); lymph node metastasis; non-small cell lung cancer (NSCLC)