Epidermal Growth Factor Receptor Is a Prognosis Predictor in Patients With Esophageal Squamous Cell Carcinoma

Zhang, Wencheng; Zhu, Hongxia; Liu, Xiao; Wang, Qifeng; Zhang, Xun; He, Jie; Sun, Kelin; Li, Xiangyang; Zhou, Zongmei; Xu, Ningzhi; Xiao, Zefen

doi:10.1016/j.athoracsur.2014.03.015

Cited by 48 publications

(49 citation statements)

References 31 publications

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“…At this stage, the role of EGFR as a predictive factor in ESCC still remained unclear. Some researchers believed that the EGFR overexpression in ESCC patients could predict prognosis 21,23,24. In this research, the patients with low expression of EGFR had better OS and DFS than those with high expression of EGFR, which was consistent with the abovementioned studies.…”

Section: Discussionsupporting

confidence: 89%

“…Although overexpression of EGFR in 40%–80% of esophageal cancer had been reported in previous literature,21,22 Jia et al15 found that the objective response rate of combined nimotuzumab and chemotherapy in ESCC was 55.6% in the EGFR-high group and 54.1% in the control group, suggesting that a high expression of EGFR in patients using nimotuzumab could not be an ideal prediction. Preexisting literature showed that an abnormal expression of EGFR was closely related to clinicopathological features such as differentiation, lymphatic metastasis, and stage 21–23. Besides lymphatic metastasis and stage, the high expression of EGFR was also significantly correlated with invasion depth in this study; however, there was no relationship between differentiation and EGFR expression.…”

Section: Discussioncontrasting

confidence: 60%

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Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

Jia¹,

Wang²,

Ji³

et al. 2016

OTT

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BackgroundBoth periostin (PN) and epidermal growth factor receptor (EGFR) can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC) still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC.Patients and methodsIn this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS) and overall survival (OS).ResultsThe high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044), differentiation grade (P=0.003), venous invasion (P=0.010), invasion depth (P=0.007), lymphatic metastasis (P=0.000), and tumor stage (P=0.000). The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000), invasion depth (P=0.022), and tumor stage (P=0.000). Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000) and DFS (P=0.000), which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS in the ESCC patients (P<0.05). Moreover, the risk of death for the ESCC patients with low expression of two biomarkers and high expression of single biomarker was 0.243 times (P=0.000) and 0.503 times (P=0.030), respectively, than that for patients with high expression of two biomarkers.ConclusionPN and EGFR are related to miscellaneous clinicopathologic characteristics. Coexpression of PN and EGFR is more closely to be of predictive value on ESCC development and progression, which may offer a novel and potential target strategy for ESCC treatment in the future.

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Section: Discussionsupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 60%

Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

Jia¹,

Wang²,

Ji³

et al. 2016

OTT

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“…Despite improvements in diagnostic approaches and the introduction of adjuvant chemotherapy, the 5-year survival rate in patients with esophageal cancer remains less than 30% (2). Previous studies have described complicated genetic and epigenetic alterations involved in ESCC progression (3,4), but the underlying mechanisms have not been fully elucidated. Therefore, to develop better approaches for ESCC diagnosis and therapy, a comprehensive understanding of the molecular variables that affect ESCC pathways is needed.…”

Section: Introductionmentioning

confidence: 99%

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Liu

Jiang

et al. 2015

Clinical Cancer Research

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Purpose: MicroRNAs (miRNA) are involved in and are controlled by epigenetic regulation, and thereby form a reciprocal regulatory circuit. Using next-generation sequencing (NGS)-based miRNA profiling, this study aimed to discover esophageal squamous cell carcinoma (ESCC)-specific miRNAs and miRNArelated epigenetic modulations.Experimental Design: NGS-based miRNA profiles were generated for four pairs of ESCC tissues and adjacent normal tissues. In situ hybridization was used to assess miRNA expression and its correlation with prognosis. miRNA-related DNA methylations were identified using bisulfite genomic sequencing, and the role of DNA methyltransferase 1 (DNMT1) was investigated using RNA interference. miRNA targets were screened by mRNA sequencing, and functional validation was performed in vitro and in vivo.Results: NGS-based miRNA profiling identified 78 differentially expressed miRNAs in ESCC. Among them, microRNA126-3p (miR-126) was significantly downregulated, and its downregulation correlated with poor ESCC prognosis. Downregulation of miR-126 was due to promoter hypermethylation of its host gene, Egfl7. DNMT1 was aberrantly upregulated in ESCC and responsible for the hypermethylation of Egfl7. Intriguingly, DNMT1 was suppressed by overexpression of miR-126, indicating the existence of a regulatory feedback circuit. ADAM9 was identified as a key target of miR-126. Ectopic expression of miR-126 or silencing of ADAM9 reduced ESCC cell proliferation and migration by inhibiting epidermal growth factor receptor-AKT signaling.Conclusions: Our results indicate that miR-126 is a potential prognostic indicator for ESCC and suggest that a novel "DNMT1-miR-126 epigenetic circuit" is involved in ESCC progression. Consequently, miR-126-based epigenetic modulations may provide a basic rationale for new approaches to antitumor therapeutics.

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“…Nonetheless, the models are limited by the retrospective nature of the data collection, which prevented the incorporation of several commonly recognized prognostic parameters (e.g. EGFR expression [56] and the circumferential resection margin [57]).…”

Section: Discussionmentioning

confidence: 99%

Nomogram and recursive partitioning analysis to predict overall survival in patients with stage IIB-III thoracic esophageal squamous cell carcinoma after esophagectomy

Zhang

et al. 2016

Oncotarget

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We have developed statistical models for predicting survival in patients with stage IIB–III thoracic esophageal squamous cell carcinoma (ESCC) and assessing the efficacy of adjuvant treatment. From a retrospective review of 3,636 patients, we created a database of 1,004 patients with stage IIB–III thoracic ESCC who underwent esophagectomy with or without postoperative radiation. Using a multivariate Cox regression model, we assessed the prognostic impact of clinical and histological factors on overall survival (OS). Logistic analysis was performed to identify factors to include in a recursive partitioning analysis (RPA) to predict 5-year OS. The nomogram was evaluated internally based on the concordance index (C-index) and a calibration plot. The median survival time in the training dataset was 30.9 months, and the 5-year survival rate was 33.9%. T stage, differentiated grade, adjuvant treatment, tumor location, lymph node metastatic ratio (LNMR), and the presence of vascular carcinomatous thrombi were statistically significant predictors of 5-year OS. The C-index of the nomogram was 0.70 (95% CI 0.67–0.73). RPA resulted in a three-class stratification: class 1, LNMR ≤ 0.15 with adjuvant treatment; class 2, LNMR ≤ 0.15 without adjuvant treatment and LNMR > 0.15 with adjuvant treatment; and class 3, LNMR > 0.15 without adjuvant treatment. The three classes were statistically significant for OS (P < 0.001). Thus, the nomogram and RPA models predicted the prognosis of stage IIB–III ESCC patients and could be used in decision-making and clinical trials.

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Epidermal Growth Factor Receptor Is a Prognosis Predictor in Patients With Esophageal Squamous Cell Carcinoma

Cited by 48 publications

References 31 publications

Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Nomogram and recursive partitioning analysis to predict overall survival in patients with stage IIB-III thoracic esophageal squamous cell carcinoma after esophagectomy

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