Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita City, Osaka, Japan.
Osaka Central Hospital, 3-3-30, Umeda, Kitaku, Osaka City, Osaka, Japan.
Sci Rep. 2024 May 26;14(1):12028. doi: 10.1038/s41598-024-62498-x.
Obesity is a risk factor for pancreatic cancer development, partly due to the tissue environment of metabolic disorder-related inflammation. We aimed to detect a tissue environment marker triggered by obesity-related metabolic disorders related to pancreatic cancer progression. In murine experiments, Bl6/j mice fed a normal diet (ND) or a high-fat diet (HFD) were orthotopically injected with mPKC1, a murine-derived pancreatic cancer cell line. We used stocked sera from 140 pancreatic cancer patients for analysis and 14 colon polyp patients as a disease control. Compared with ND-fed mice, HFD-fed mice exhibited obesity, larger tumors, and worse prognoses. RNA sequencing of tumors identified tenascin C (TNC) as a candidate obesity-related serum tissue environment marker with elevated expression in tumors of HFD-fed mice. Serum TNC levels were greater in HFD-fed mice than in ND-fed mice. In pancreatic cancer patients, serum TNC levels were greater than those in controls. The TNC-high group had more metabolic disorders and greater CA19-9 levels than did the TNC-low group. There was no relationship between serum TNC levels and disease stage. Among 77 metastatic patients treated with chemotherapy, a high serum TNC concentration was an independent poor prognostic factor. Pancreatic cancer patients with high serum TNC levels experienced progression more rapidly.
肥胖是胰腺癌发展的一个风险因素,部分原因是与代谢紊乱相关的炎症的组织环境。我们旨在检测与肥胖相关的代谢紊乱相关的组织环境标记物,这些标记物与胰腺癌的进展有关。在小鼠实验中,将 Bl6/j 小鼠用正常饮食(ND)或高脂肪饮食(HFD)进行同源注射,使用来源于 140 名胰腺癌患者的储存血清进行分析,并用 14 名结肠息肉患者作为疾病对照。与 ND 喂养的小鼠相比,HFD 喂养的小鼠表现出肥胖、更大的肿瘤和更差的预后。肿瘤的 RNA 测序将 tenascin C(TNC)鉴定为候选肥胖相关血清组织环境标记物,其在 HFD 喂养的小鼠肿瘤中的表达升高。HFD 喂养的小鼠血清 TNC 水平高于 ND 喂养的小鼠。在胰腺癌患者中,血清 TNC 水平高于对照组。TNC 高水平组比 TNC 低水平组有更多的代谢紊乱和更高的 CA19-9 水平。血清 TNC 水平与疾病阶段之间没有关系。在 77 名接受化疗治疗的转移性患者中,高血清 TNC 浓度是独立的不良预后因素。血清 TNC 水平高的胰腺癌患者进展更快。