title: Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients.
abstract: Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: De-Qing
authors.initials: DQ
authors.lastname: Liu
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Li
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Jiang-Bo
authors.initials: JB
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Affiliated Hospital of Luzhou Medical College, 319 Zhongshan Road, Luzhou, 646000, China.
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Zhou
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Wen-Qiong
authors.initials: WQ
authors.lastname: Xue
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zheng
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Chen
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liao
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Shao-Dan
authors.initials: SD
authors.lastname: Zhang
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Ye-Zhu
authors.initials: YZ
authors.lastname: Hu
authors.affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D014746:Vimentin / Q000737:chemistry / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005353:Fibronectins; D034741:RNA, Small Interfering; D014746:Vimentin; C417187:RIPK4 protein, human; D017346:Protein Serine-Threonine Kinases; D020778:Matrix Metalloproteinase 2