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预测胰腺癌 S-1 辅助化疗效果的新型候选因素。

Novel candidate factors predicting the effect of S-1 adjuvant chemotherapy of pancreatic cancer.

机构信息

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

Sci Rep. 2021 Mar 22;11(1):6541. doi: 10.1038/s41598-021-86099-0.

Abstract

The collagen gel droplet-embedded drug sensitivity test (CD-DST) was revealed to be useful for predicting the effect of S-1 adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC). However, collection of an adequate number of PDAC cells is difficult due to the surrounding fibroblasts. Thus, the aim of this study was to discover novel biomarkers to predict chemosensitivity based on the CD-DST results. Proteomics analysis was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Candidate proteins were validated in patients with 5-FU CD-DST results via immunohistochemistry (IHC). The relationships between the candidate proteins and the effect of the adjuvant S-1 were investigated via IHC. Among the 2696 proteins extracted by LC-MS/MS, C1TC and SAHH could accurately predict the CD-DST results. Recurrence-free survival (RFS) was significantly improved in the IHC-positive group compared with the IHC-negative group in both factors. The negative group did not show a significant difference from the group that did not receive S-1. The double-positive group was associated with significantly prolonged RFS compared to the no adjuvant chemotherapy group. C1TC and SAHH have been shown to be useful biomarkers for predicting 5-FU sensitivity as a substitute for the CD-DST in adjuvant chemotherapy for PDAC.

摘要

胶原凝胶微滴药物敏感性测试(CD-DST)被证明对预测胰腺导管腺癌(PDAC)患者 S-1 辅助化疗的效果有用。然而,由于周围的成纤维细胞,收集足够数量的 PDAC 细胞是困难的。因此,本研究旨在发现基于 CD-DST 结果预测化疗敏感性的新型生物标志物。使用液相色谱串联质谱(LC-MS/MS)进行蛋白质组学分析。通过免疫组织化学(IHC)在具有 5-FU CD-DST 结果的患者中验证候选蛋白。通过 IHC 研究候选蛋白与辅助 S-1 效果之间的关系。在 LC-MS/MS 提取的 2696 种蛋白质中,C1TC 和 SAHH 可以准确预测 CD-DST 结果。在两个因素中,IHC 阳性组的无复发生存率(RFS)明显优于 IHC 阴性组。阴性组与未接受 S-1 治疗的组之间无显著差异。与未接受辅助化疗的组相比,双阳性组的 RFS 明显延长。C1TC 和 SAHH 已被证明是预测 PDAC 辅助化疗中 5-FU 敏感性的有用生物标志物,可以替代 CD-DST。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e232/7985196/c735d9b4f0a6/41598_2021_86099_Fig1_HTML.jpg

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