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一种分子预后模型可预测食管鳞状细胞癌的预后。

A molecular prognostic model predicts esophageal squamous cell carcinoma prognosis.

作者信息

Cao Hui-Hui, Zheng Chun-Peng, Wang Shao-Hong, Wu Jian-Yi, Shen Jin-Hui, Xu Xiu-E, Fu Jun-Hui, Wu Zhi-Yong, Li En-Min, Xu Li-Yan

机构信息

The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, China.

Departments of Oncology Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong, China.

出版信息

PLoS One. 2014 Aug 25;9(8):e106007. doi: 10.1371/journal.pone.0106007. eCollection 2014.

Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.

METHODS

We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset).

RESULTS

The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.

CONCLUSIONS

This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

摘要

背景

食管鳞状细胞癌(ESCC)在中国具有最高的死亡率。尽管手术切除和辅助放化疗等治疗方法有所改进,但ESCC的5年生存率仍然很低,而且目前的临床分期方法在有效区分患者治疗方案方面能力有限。因此,本研究的目的是开发一种基于免疫组织化学的预后模型,以改善ESCC患者的临床风险评估。

方法

我们基于表皮生长因子受体(EGFR)、磷酸化特异性蛋白1(p-Sp1)和Fascin蛋白轴的联合表达开发了一种分子预后模型。对130例福尔马林固定、石蜡包埋的食管根治性切除标本(生成数据集)分析了该预后模型的存在情况及相关临床结果,并使用185例标本的独立队列(验证数据集)进行了验证。

结果

利用这三个基因在蛋白质水平的表达构建了一个分子预后模型,该模型在生成数据集和验证数据集中均能高度预测ESCC的生存情况(P = 0.001)。回归分析表明,该分子预后模型对总生存具有强烈且独立预测作用(风险比 = 2.358 [95% CI,1.391 - 3.996],在生成数据集中P = 0.001;风险比 = 1.990 [95% CI,1.256 - 3.154],在验证数据集中P = 0.003)。此外,这3种生物标志物联合使用的预测能力比单个生物标志物更强。

结论

这种技术上简单的基于免疫组织化学的分子模型能准确预测ESCC患者的生存情况,因此可作为当前临床风险分层方法的补充。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe78/4143329/9f7269753b84/pone.0106007.g001.jpg

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