Nakamura Yasuhiro, Yasukawa Takehiro, Fukumura Yuki, Takeda Yoshinori, Imamura Hiroshi, Shi Yang, Li Mu, Abe Masaaki, Uyama Saya, Kajino Kazunori, Ishijima Muneaki, Saiura Akio, Orimo Akira
Department of Orthopaedics, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Jpn J Clin Oncol. 2024 Dec 7;54(12):1261-1271. doi: 10.1093/jjco/hyae118.
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.
胰腺导管腺癌（PDAC）由于手术可切除性低和对化疗耐药，预后较差。丰富的间质是PDAC的特征，癌症相关成纤维细胞（CAFs）是主要的间质成分，导致化疗耐药。由于新辅助化疗（NAC）作为标准方案纳入PDAC治疗，必须研究CAFs在NAC耐药中的作用。虽然IV型胶原（COLIV）存在于PDAC肿瘤中，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患者队列，检查临床病理数据，并对手术切除的胰腺制备的组织标本进行COLIV免疫组化分析。
我们的分析显示，约50%的病例间质中COLIV呈阳性，弥漫性COLIV染色是独立的不良预后因素，与NAC治疗前高血清CA19-9（>37 U/mL）和术后残留肿瘤一起。基于这些发现，我们提出间质COLIV染色可用于预测NAC治疗的PDAC患者术后的预后。此外，这些发现提示间质COLIV染色可能表明对抗癌药物耐药和/或促成PDAC的恶性程度。
