Dataset Information

Downregulation of 14-3-3? correlates with multistage carcinogenesis and poor prognosis of esophageal squamous cell carcinoma.

ABSTRACT:

Aims

The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3? protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis.

Materials and methods

Western blot was used to examine 14-3-3? protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to IV stage and various esophageal epithelial cell lines with different biological behavior. Immunohistochemistry was used to estimate 14-3-3? protein in 110 biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had follow-up data. Support vector machine (SVM) was used to develop a classifier for prognosis.

Results

14-3-3? decreased progressively from NEE to LGIN, to HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed high expression of 14-3-3? protein compared with non-chemoresistant ESCC cell lines and immortalized NEC. Furthermore, the downregulation of 14-3-3? correlated significantly with histological grade (P?=?0.000) and worse prognosis (P?=?0.004). Multivariate Cox regression analysis indicated that 14-3-3? protein (P?=?0.016) and T stage (P?=?0.000) were independent prognostic factors for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological grade, lymph node metastasis, clinical stage and 14-3-3?, distinguished significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P?=?0.000).

Conclusions

Downregulation of 14-3-3? arises early in the development of ESCC and predicts poor survival, suggesting that 14-3-3? may be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. Our seven-feature SVM classifier for ESCC prognosis may help to inform clinical decisions and tailor individual therapy.

SUBMITTER: Qi YJ

PROVIDER: S-EPMC3990633 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Downregulation of 14-3-3σ correlates with multistage carcinogenesis and poor prognosis of esophageal squamous cell carcinoma.

Qi Yi-Jun YJ Wang Ming M Liu Rui-Min RM Wei Hua H Chao Wei-Xia WX Zhang Tian T Lou Qiang Q Li Xiu-Min XM Ma Jin J Zhu Han H Yang Zhen-Hua ZH Liu Hai-Qing HQ Ma Yuan-Fang YF

PloS one 20140417 4

<h4>Aims</h4>The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis.<h4>Materials and methods</h4>Western blot was used to examine 14-3-3σ protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade in ...[more]

PMID: 24743601

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