title: PFN2, a novel marker of unfavorable prognosis, is a potential therapeutic target involved in esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressively malignant tumors with dismal prognosis. Profilin 2 (PFN2) is an actin-binding protein that regulates the dynamics of actin polymerization and plays a key role in cell motility. Recently, PFN2 have emerged as significant regulators of cancer processes. However, the clinical significance and biological function of PFN2 in ESCC remain unclear.
  
  
  
  PFN2 protein expression was validated by immunohistochemistry (IHC) on tissue microarray from Chinese Han and Kazakh populations with ESCC. The associations among PFN2 expression, clinicopathological features, and prognosis of ESCC were analyzed. The effects on cell proliferation, invasion and migration were examined using MTT and Transwell assays. Markers of epithelial-mesenchymal transition (EMT) were detected by Western blot analysis.
  
  
  
  Compared with normal esophageal epithelium (NEE), PFN2 protein expression was markedly increased in low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and ESCC, increased gradually from LGIN to ESCC, and finally reached high grade in HGIN in the Han population. Similarly, PFN2 protein was more overexpressed in ESCC than in NEE in the Kazakh population. The results of Western blot analysis also showed that PFN2 expression was significantly higher in the ESCC tissue than in a matched adjacent non-cancerous tissue. PFN2 expression was positively correlated with invasion depth and lymph node metastasis. High PFN2 expression was significantly correlated with short overall survival (OS) (P = 0.023). Cox regression analysis revealed that PFN2 expression was an independent prognostic factor for poor OS in ESCC. Downregulation of PFN2 inhibited, rather than proliferated, cell invasion and migration, as well as induced an EMT phenotype, including increased expression of epithelial marker E-cadherin, decreased mesenchymal marker Vimentin, Snail, Slug and ZEB1, and morphological changes in ESCC cells in vitro.
  
  
  
  Our findings demonstrate that PFN2 has a novel role in promoting ESCC progression and metastasis and portending a poor prognosis, indicating that PFN2 could act as an early biomarker of high-risk population. Targeting PFN2 may offer a promising therapeutic strategy for ESCC treatment.
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.|Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Cui
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Shu-Mao
authors.initials: SM
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, Zhengzhou First People's Hospital, Zhengzhou, 450000, China.
authors.forename: Yue-Xun
authors.initials: YX
authors.lastname: Xu
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Dang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Liu
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Liang-Hai
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Hu
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Liang
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Jiang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, 832002, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of CT and MRI, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, 832002, China. 24363941@qq.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China. cyz0515@sina.com.
authors.forename: Yun-Zhao
authors.initials: YZ
authors.lastname: Chen
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, 832002, China. lifeng7855@126.com.|Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China. lifeng7855@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005006:Ethnicity; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D051304:Profilins / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000378:metabolism; D012372:ROC Curve; D014162:Transfection; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D051304:Profilins; D034741:RNA, Small Interfering
keywords: ESCC; Metastasis; Precursor lesions; Profilin 2; Prognosis