PFN2, a novel marker of unfavorable prognosis, is a potential therapeutic target involved in esophageal squamous cell carcinomaReport as inadecuate




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Journal of Translational Medicine

, 14:137

Disease Biomarkers

Abstract

BackgroundEsophageal 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.

MethodsPFN2 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.

ResultsCompared 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.

ConclusionsOur 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.

KeywordsProfilin 2 ESCC Precursor lesions Prognosis Metastasis AbbreviationsESCCesophageal squamous cell carcinoma

PFN2profilin 2

IHCimmunohistochemistry

EMTepithelial–mesenchymal transition

NEEnormal esophageal epithelium

LGINlow-grade intraepithelial neoplasia

HGINhigh-grade intraepithelial neoplasia

ESINesophageal squamous intraepithelial neoplasia

OSoverall survival

OSCCoral squamous cell carcinoma

TNMtumor node metastasis

TMAtissue microarray

HEhematoxylin and eosin

ISimmunohistochemistry score

ROCreceiver operating characteristic

Xiao-bin Cui and Shu-mao Zhang contributed equally to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-0884-y contains supplementary material, which is available to authorized users.

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Author: Xiao-bin Cui - Shu-mao Zhang - Yue-xun Xu - Hong-wei Dang - Chun-xia Liu - Liang-hai Wang - Lan Yang - Jian-ming Hu - Wei-

Source: https://link.springer.com/







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