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

基质 IV 型胶原与新辅助化疗治疗的胰腺癌预后的关系

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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

Background

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.

Conclusions

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.

Methods

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.

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