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RPN2 表达预测食管鳞癌对多西他赛的反应。

RPN2 expression predicts response to docetaxel in oesophageal squamous cell carcinoma.

机构信息

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo, Japan.

出版信息

Br J Cancer. 2012 Oct 9;107(8):1233-8. doi: 10.1038/bjc.2012.396. Epub 2012 Sep 6.

Abstract

BACKGROUND

Neoadjuvant chemotherapy - often using docetaxel in various combinatorial regimens - is a standard treatment choice for advanced oesophageal squamous cell carcinoma (ESCC) in Japan. However, no useful markers exist that predict docetaxel's effects on ESCC. Ribophorin II (RPN2) silencing, which reduces glycosylation of P-glycoproteins and decreases membrane localisation, promotes docetaxel-dependent apoptosis. We investigated whether RPN2 expression in ESCC biopsy specimens could be a predictive biomarker in docetaxel-based neoadjuvant chemotherapy.

METHODS

We evaluated RPN2 expression immunohistochemically in biopsy specimens from 79 patients with node-positive ESCC, who received docetaxel-based adjuvant chemotherapy, and compared clinical and pathological responses between the RPN2-positive and RPN2-negative groups. We also studied susceptibility of RPN2-suppressed ESCC cells to docetaxel.

RESULTS

The RPN2-negative group had better clinical and pathological responses to docetaxel than the RPN2-positive group. We also found RPN2 suppression to alter docetaxel susceptibility in vitro.

CONCLUSION

Expression of RPN2 in biopsy specimens could be a useful predictive marker for response to docetaxel-based neoadjuvant chemotherapy in ESCC.

摘要

背景

新辅助化疗——常采用多西紫杉醇联合各种方案——是日本晚期食管鳞癌(ESCC)的标准治疗选择。然而,目前尚不存在预测多西紫杉醇对 ESCC 疗效的有用标志物。核糖蛋白 II(RPN2)沉默可减少 P 糖蛋白的糖基化,减少其膜定位,从而促进多西紫杉醇依赖性细胞凋亡。我们研究了 ESCC 活检标本中 RPN2 的表达是否可以作为基于多西紫杉醇的新辅助化疗的预测生物标志物。

方法

我们采用免疫组织化学方法检测了 79 例接受多西紫杉醇辅助化疗的淋巴结阳性 ESCC 患者活检标本中 RPN2 的表达情况,并比较了 RPN2 阳性和 RPN2 阴性组的临床和病理反应。我们还研究了 RPN2 抑制对 ESCC 细胞对多西紫杉醇敏感性的影响。

结果

RPN2 阴性组对多西紫杉醇的临床和病理反应优于 RPN2 阳性组。我们还发现 RPN2 抑制可改变 ESCC 细胞对多西紫杉醇的敏感性。

结论

活检标本中 RPN2 的表达可能是 ESCC 患者基于多西紫杉醇的新辅助化疗反应的有用预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9d0/3494434/6e74cb294a3d/bjc2012396f1.jpg

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