ZNF750 Expression as a Novel Candidate Biomarker of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma.

ZNF750, an epidermal differentiation regulator, has been suggested to act as a tumor suppressor of esophageal squamous cell carcinoma (ESCC). Although a correlation between the epidermal differentiation gene and resistance to chemoradiotherapy (CRT) has been posited, no data regarding the ZNF750 status in ESCC have been reported. The aim of the present study was to evaluate the relationship between ZNF750 expression and response to CRT in ESCC. Eighty-seven patients who had been pathologically diagnosed with ESCC were evaluated in the present study. All patients underwent neoadjuvant CRT, followed by curative esophagectomy. The expression of ZNF750 in pretreatment biopsy samples was immunohistochemically investigated and compared to the histopathological effectiveness of CRT in surgical specimens. High expression of ZNF750 was closely correlated with good sensitivity to CRT (p = 0.016). A univariate analysis showed that high/intermediate expression of ZNF750 was a significant predictive factor for good sensitivity to CRT (p = 0.006). High/intermediate expression of ZNF750 (30% or more) remained an independent predictive factor for sensitivity to CRT in a multivariate analysis (p = 0.033). ZNF750 expression predicts sensitivity to CRT and can be a biomarker that reliably predicts the response of ESCC to CRT.

Otsuka R ，Akutsu Y ，Sakata H ，Hanari N ，Murakami K ，Kano M ，Takahashi M ，Matsumoto Y ，Sekino N ，Yokoyama M ，Iida K ，Matsubara H ... -  《-》

ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma.

ZNF750, a transcriptional regulator of epidermal differentiation, has been identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the clinical and prognostic significance of ZNF750 expression and to evaluate the effect of ZNF750 knockdown on cell proliferation, migration, and invasion in ESCC. A total of 124 patients with ESCC who underwent curative esophagectomy were evaluated in this study. The expression of ZNF750 in surgical specimens was immunohistochemically assessed and used in the analysis of clinicopathological features and overall survival (OS). The molecular role of ZNF750 was investigated by ZNF750 knockdown using small interfering RNA (siRNA) in ESCC cell lines. Low ZNF750 expression had a significant correlation with positive lymph node metastasis (p = 0.028). Furthermore, there was a significant relationship between low expression of ZNF750 in ESCC and a poor OS, and a multivariate analysis showed that low ZNF750 expression was an independent prognostic factor (p = 0.020). The cell growth, migration, and invasion were significantly increased by downregulation of ZNF750. The low expression of ZNF750 was significantly associated with a poor prognosis, and ZNF750 expression may, therefore, be a reliable prognostic biomarker in ESCC.

Otsuka R ，Akutsu Y ，Sakata H ，Hanari N ，Murakami K ，Kano M ，Toyozumi T ，Takahashi M ，Matsumoto Y ，Sekino N ，Yokoyama M ，Okada K ，Shiraishi T ，Komatsu A ，Iida K ，Matsubara H ... -  《-》

Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer.

Zhang JL ，Wang HY ，Yang Q ，Lin SY ，Luo GY ，Zhang R ，Xu GL ... -  《-》

MiRNA Expression Analysis of Pretreatment Biopsies Predicts the Pathological Response of Esophageal Squamous Cell Carcinomas to Neoadjuvant Chemoradiotherapy.

Wen J ，Luo K ，Liu H ，Liu S ，Lin G ，Hu Y ，Zhang X ，Wang G ，Chen Y ，Chen Z ，Li Y ，Lin T ，Xie X ，Liu M ，Wang H ，Yang H ，Fu J ... -  《-》

Gene expression analysis of pretreatment biopsies predicts the pathological response of esophageal squamous cell carcinomas to neo-chemoradiotherapy.

Neoadjuvant chemoradiotherapy (neo-CRT) followed by surgery has been shown to improve esophageal squamous cell carcinoma (ESCC) patients' survival compared with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method can currently predict CRT response. In this study, we aim to identify mRNA markers useful for ESCC CRT-response prediction. Gene expression analyses were carried out on pretreated cancer biopsies from 28 ESCCs who received neo-CRT and surgery. Surgical specimens were assessed for pathological response to CRT. The differentially expressed genes identified by expression profiling were validated by real-time quantitative polymerase chain reaction (qPCR), and a classifying model was built from qPCR data using Fisher's linear discriminant analysis. The predictive power of this model was further assessed in a second set of 32 ESCCs. The profiling of the 28 ESCCs identified 10 differentially expressed genes with more than a twofold change between patients with pathological complete response (pCR) and less than pCR (<pCR). A prediction model based on the qPCR values of three genes was generated, which provided a predictive accuracy of 86% upon leave-one-out cross-validation. Furthermore, the predictive power of this model was validated in another cohort of 32 ESCCs, among which a predictive accuracy of 81% was achieved. Importantly, the discriminant score was found to be the only independent factor that affected neo-CRT response in both the training (P = 0.015) and validation (P = 0.017) sets, respectively. The expression levels of three genes determined by qPCR provide a possible model for ESCC CRT prediction, which will facilitate the individualization of ESCC treatment. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power.

Wen J ，Yang H ，Liu MZ ，Luo KJ ，Liu H ，Hu Y ，Zhang X ，Lai RC ，Lin T ，Wang HY ，Fu JH ... -  《-》