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高基质 SPARC 表达与接受吉西他滨联合 S-1 辅助治疗或单独接受吉西他滨辅助治疗的可切除胰腺导管腺癌患者的不良生存独立相关。

The high stromal SPARC expression is independently associated with poor survival of patients with resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine in combination with S-1 or adjuvant gemcitabine alone.

机构信息

Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

出版信息

Pancreatology. 2018 Mar;18(2):191-197. doi: 10.1016/j.pan.2017.12.014. Epub 2017 Dec 26.

Abstract

BACKGROUND

Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential.

OBJECTIVES

To investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone).

METHODS

Stromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed.

RESULTS

In multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P < .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS.

CONCLUSIONS

High stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.

摘要

背景

尽管术后辅助化疗可改善胰腺导管腺癌(PDAC)患者的生存,但疗效在个体间存在差异。寻找能够预测 PDAC 患者辅助化疗疗效的生物标志物至关重要。

目的

探讨富含半胱氨酸的酸性分泌蛋白(SPARC)在接受吉西他滨联合 S-1(辅助 GS)或单独吉西他滨(辅助 G 单独)辅助化疗的 PDAC 患者中的表达情况,评估其对 PDAC 患者辅助化疗疗效的预测价值。

方法

对 211 例行辅助 GS 或 G 单独化疗的 PDAC 患者的肿瘤组织标本进行免疫组化检测,分析 SPARC 表达与临床病理特征、无病生存(DFS)和总生存(OS)的关系。

结果

多因素分析显示,边缘可切除伴动脉侵犯(BR-A)(P=0.002)、术前 CA 19-9 水平较高(≥91 U/ml)(P=0.005)、中低分化(P=0.003)、淋巴结转移(P=0.012)和间质 SPARC 高表达(P=0.013)是 DFS 较差的独立预测因素。此外,BR-A(P=0.003)、术前 CA 19-9 水平较高(≥91 U/ml)(P=0.007)和间质 SPARC 高表达(P<0.001)是 OS 较差的独立预测因素。而细胞质 SPARC 表达与 DFS 和 OS 无关。

结论

间质 SPARC 高表达是接受辅助 GS 或 G 单独化疗的 PDAC 患者 DFS 和 OS 较差的独立预测因素。间质 SPARC 表达可能是预测接受辅助 GS 或 G 单独化疗的 PDAC 患者预后的一个相关生物标志物。

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