Journal Article

The serum tenascin C level is a marker of metabolic disorder-related inflammation affecting pancreatic cancer prognosis

Kudo, Shinnosuke, Fukumoto, Kenji, Yoshioka, Teppei, Sasaki, Yutaka, Nishio, Akira, Sung, Jihyun, Tatsumi, Tomohide, Soma, Kazumasa, Shigekawa, Minoru, Sasaki, Yoichi, Murai, Kazuhiro, Shirai, Kumiko, Hikita, Hayato, Sato, Katsuhiko, Kodama, Takahiro, Tahata, Yuki, Kato, Seiya, Saito, Yoshinobu, Yamauchi, Ryohei, Takehara, Tetsuo

2024

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/67/1504/1713 / 631/67/2195 / Aged / Animals / Biomarkers, Tumor - blood / Cell Line, Tumor / Chemotherapy / Diet, High-Fat - adverse effects / Disease control / Female / High fat diet / Humanities and Social Sciences / Humans / Inflammation / Inflammation - blood / Male / Medical prognosis / Metabolic Diseases - blood / Metabolic disorders / Metastases / Mice / Mice, Inbred C57BL / Middle Aged / multidisciplinary / Obesity / Obesity - blood / Obesity - complications / Pancreatic cancer / Pancreatic Neoplasms - blood / Pancreatic Neoplasms - pathology / Polyps / Prognosis / Risk factors / Science / Science (multidisciplinary) / Tenascin / Tenascin - blood / Tenascin C / Tumors