High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer

Autoři: Ryotaro Ohkuma aff001;  Erica Yada aff004;  Shumpei Ishikawa aff005;  Daisuke Komura aff005;  Hidenobu Ishizaki aff006;  Koji Tamada aff007;  Yutaro Kubota aff002;  Kazuyuki Hamada aff002;  Hiroo Ishida aff002;  Yuya Hirasawa aff002;  Hirotsugu Ariizumi aff002;  Etsuko Satoh aff002;  Midori Shida aff001;  Makoto Watanabe aff001;  Rie Onoue aff001;  Kiyohiro Ando aff001;  Junji Tsurutani aff002;  Kiyoshi Yoshimura aff002;  Takehiko Yokobori aff011;  Tetsuro Sasada aff004;  Takeshi Aoki aff012;  Masahiko Murakami aff012;  Tomoko Norose aff013;  Nobuyuki Ohike aff013;  Masafumi Takimoto aff013;  Masahiko Izumizaki aff003;  Shinichi Kobayashi aff009;  Takuya Tsunoda aff002;  Satoshi Wada aff001
Působiště autorů: Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan aff001;  Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, Tokyo, Japan aff002;  Department of Physiology, Graduate School of Medicine, Showa University, Tokyo, Japan aff003;  Kanagawa Cancer Center Research Institute, Kanagawa, Japan aff004;  Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan aff005;  Noile-Immune Biotech, Inc., Tokyo, Japan aff006;  Department of Immunology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan aff007;  Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan aff008;  Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan aff009;  Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan aff010;  Department of Innovative Immune-Oncology Therapeutics, Graduate School of Medicine, Gunma University, Gunma, Japan aff011;  Department of Surgery, Division of General and Gastroenterological Surgery, School of Medicine, Showa University, Tokyo, Japan aff012;  Department of Pathology and Laboratory Medicine, School of Medicine, Showa University, Tokyo, Japan aff013
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0226707


Pancreatic cancer has an extremely poor prognosis, and identification of novel predictors of therapeutic efficacy and prognosis is urgently needed. Chemoresistance-related molecules are correlated with poor prognosis and may be effective targets for cancer treatment. Here, we aimed to identify novel molecules correlated with chemoresistance and poor prognosis in pancreatic cancer. We established 10 patient-derived xenograft (PDX) lines from patients with pancreatic cancer and performed next-generation sequencing (NGS) of tumor tissues from PDXs after treatment with standard drugs. We established a gene-transferred tumor cell line to express chemoresistance-related molecules and analyzed the chemoresistance of the established cell line against standard drugs. Finally, we performed immunohistochemical (IHC) analysis of chemoresistance-related molecules using 80 pancreatic cancer tissues. From NGS analysis, we identified olfactomedin-4 (OLFM4) as having high expression in the PDX group treated with anticancer drugs. In IHC analysis, OLFM4 expression was also high in PDXs administered anticancer drugs compared with that in untreated PDXs. Chemoresistance was observed by in vitro analysis of tumor cell lines with forced expression of OLFM4. In an assessment of tissue specimens from 80 patients with pancreatic cancer, Kaplan-Meier analysis showed that patients in the low OLFM4 expression group had a better survival rate than patients in the high OLFM4 expression group. Additionally, multivariate analysis showed that high expression of OLFM4 was an independent prognostic factor predicting poor outcomes. Overall, our study revealed that high expression of OLFM4 was involved in chemoresistance and was an independent prognostic factor in pancreatic cancer. OLFM4 may be a candidate therapeutic target in pancreatic cancer.

Klíčová slova:

Adenocarcinomas – Cancer detection and diagnosis – Cancer chemotherapy – Cancer treatment – Differentiated tumors – Mouse models – Pancreatic cancer – Prognosis


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