研究动态
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基质 IV 型胶原蛋白与新辅助化疗治疗的胰腺癌预后的关系。

Association of stromal type IV collagen and prognosis in neoadjuvant chemotherapy-treated pancreatic cancer.

发表日期:2024 Aug 24
作者: Yasuhiro Nakamura, Takehiro Yasukawa, Yuki Fukumura, Yoshinori Takeda, Hiroshi Imamura, Yang Shi, Mu Li, Masaaki Abe, Saya Uyama, Kazunori Kajino, Muneaki Ishijima, Akio Saiura, Akira Orimo
来源: MOLECULAR & CELLULAR PROTEOMICS

摘要:

胰腺导管腺癌(PDAC)由于手术资格低且对化疗耐药,预后较差。丰富的基质是 PDAC 的特征,癌症相关成纤维细胞 (CAF) 是主要的基质成分,有助于化疗耐药。由于新辅助化疗 (NAC) 作为标准方案包含在 PDAC 治疗中,因此必须研究 CAF 在 NAC 耐药中的作用。尽管 PDAC 肿瘤中存在 IV 型胶原蛋白 (COLIV),但 COLIV 与 NAC 治疗的 PDAC 疾病进展之间的关联尚不清楚。我们使用一组接受 NAC 治疗的 PDAC 患者,检查了临床病理学数据,并对以下患者进行了免疫组织化学分析:从手术切除的胰腺中制备的组织标本中存在 COLIV。我们的分析显示,约 50% 的病例间质中 COLIV 呈阳性,弥漫性 COLIV 染色是一个独立的不良预后因素,与 NAC 治疗前高血清 CA19-9 一起 (>37 U /mL) 和术后残留肿瘤。基于这些发现,我们建议基质 COLIV 染色可用于预测接受 NAC 治疗的 PDAC 患者术后的预后。此外,这些发现表明基质 COLIV 染色可能表明 PDAC 对抗癌药物产生耐药性和/或导致 PDAC 发生恶性肿瘤。© 作者 2024。由牛津大学出版社出版。
Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to its low surgical eligibility and resistance to chemotherapy. Abundant stroma is characteristic of PDAC, and cancer-associated fibroblasts (CAFs) are a major stromal constituent, contributing to chemoresistance. Because neoadjuvant chemotherapy (NAC) is included in PDAC treatment as a standard regimen, the role of CAFs in NAC resistance must be studied. Although type IV collagen (COLIV) is present in the tumor of PDAC, the association between COLIV and disease advancement of NAC-treated PDAC is unclear.Using a cohort of NAC-treated patients with PDAC, we examined clinicopathological data and conducted immunohistochemical analysis of COLIV in tissue specimens prepared from surgically resected pancreas.Our analysis revealed that ~50% of the cases were positive for COLIV in the stroma and diffuse COLIV staining was an independent poor prognosis factor alongside high serum CA19-9 before NAC treatment (>37 U/mL) and postsurgical residual tumors. Based on these findings, we propose that stromal COLIV staining can be used to predict prognosis in NAC-treated patients with PDAC after surgery. Additionally, these findings suggest a possibility that stromal COLIV staining indicates resistance to anticancer drugs and/or contributes to malignancy in PDAC.© The Author(s) 2024. Published by Oxford University Press.