title: Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma.
abstract: Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC.
authors.affiliation: Cancer Research Centre, Shantou University Medical College, Shantou 515063, China. gjf88900406@126.com.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Gan
authors.affiliation: Department of Information, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China. zyl88900406@126.com.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Research Centre, Shantou University Medical College, Shantou 515063, China. kxr_2014_88900406@126.com.|Department of Biotherapy, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China. kxr_2014_88900406@126.com.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Ke
authors.affiliation: Department of General Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China. cht_22003@126.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Pathology, Central Hospital of Kaifeng, Kaifeng 475000, China. hongzh_ren@126.com.
authors.forename: Hongzheng
authors.initials: H
authors.lastname: Ren
authors.affiliation: Cancer Research Centre, Shantou University Medical College, Shantou 515063, China. dhm88900406@126.com.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dong
authors.affiliation: Cancer Research Centre, Shantou University Medical College, Shantou 515063, China. jjl_2014_88900406@126.com.|Department of Biotherapy, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China. jjl_2014_88900406@126.com.
authors.forename: Jiali
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Thoracic Surgery, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China. shbin2442_c@126.com.
authors.forename: Shaobin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Tumor Tissue Bank, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China. zyx88900406@126.com.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Cancer Research Centre, Shantou University Medical College, Shantou 515063, China. haozhang@stu.edu.cn.|Department of Biotherapy, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China. haozhang@stu.edu.cn.|Tumor Tissue Bank, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China. haozhang@stu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004249:DNA Damage; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: C468783:H2AX protein, human; D006657:Histones; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: DNA damage; metastasis; p21-activated kinase 1; primary esophageal small cell carcinoma; prognosis; γH2AX