Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma

Masahiko Kubo, Kunihito Gotoh, Hidetoshi Eguchi, Shogo Kobayashi, Yoshifumi Iwagami, Yoshito Tomimaru, Hirofumi Akita, Tadafumi Asaoka, Takehiro Noda, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki

Research output: Contribution to journalArticle

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Abstract

Background: CD36, a multi-ligand scavenger receptor, has been associated with several cancers. Many studies have revealed that CD36 contributed to cancer malignancy. This study aimed to reveal the function of CD36 expression in pancreatic ductal adenocarcinoma (PDAC). Methods: CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with PDAC. We divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. Gemcitabine-resistant (GR) PDAC cell lines were transfected with small interfering RNA (siRNA) that specifically targeted CD36 to evaluate chemoresistance and apoptosis. Results: In resected PDAC samples, CD36 expression was significantly correlated with microinvasion into the venous system (p = 0.0284). Patients with high CD36 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates than patients with low expression; thus, CD36 was an independent prognostic factor for OS and RFS. In subgroup analyses, CD36 was an independent risk factor for OS and RFS in 59 patients treated with gemcitabine adjuvant chemotherapy. CD36 expression was upregulated in PDAC–GR cell lines compared with the PDAC parent cell line. Transduction with siRNA downregulated CD36, which reduced PDAC cell resistance to gemcitabine and inhibited anti-apoptosis proteins. Conclusion: CD36 expression influenced gemcitabine resistance by regulating anti-apoptosis proteins. High CD36 expression was a significant, unfavorable prognostic factor in PDAC. Anti-CD36 treatment might serve as an optional treatment for lowering resistance to gemcitabine.

Original languageEnglish
JournalAnnals of Surgical Oncology
DOIs
Publication statusAccepted/In press - Jan 1 2019

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gemcitabine
Adenocarcinoma
Survival
Cell Line
Apoptosis
Recurrence
Small Interfering RNA
Scavenger Receptors
Neoplasms
Adjuvant Chemotherapy
Proteins
Down-Regulation
Survival Rate
Immunohistochemistry
Ligands
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Kubo, M., Gotoh, K., Eguchi, H., Kobayashi, S., Iwagami, Y., Tomimaru, Y., ... Doki, Y. (Accepted/In press). Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma. Annals of Surgical Oncology. https://doi.org/10.1245/s10434-019-07927-2

Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma. / Kubo, Masahiko; Gotoh, Kunihito; Eguchi, Hidetoshi; Kobayashi, Shogo; Iwagami, Yoshifumi; Tomimaru, Yoshito; Akita, Hirofumi; Asaoka, Tadafumi; Noda, Takehiro; Takeda, Yutaka; Tanemura, Masahiro; Mori, Masaki; Doki, Yuichiro.

In: Annals of Surgical Oncology, 01.01.2019.

Research output: Contribution to journalArticle

Kubo, M, Gotoh, K, Eguchi, H, Kobayashi, S, Iwagami, Y, Tomimaru, Y, Akita, H, Asaoka, T, Noda, T, Takeda, Y, Tanemura, M, Mori, M & Doki, Y 2019, 'Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma', Annals of Surgical Oncology. https://doi.org/10.1245/s10434-019-07927-2
Kubo, Masahiko ; Gotoh, Kunihito ; Eguchi, Hidetoshi ; Kobayashi, Shogo ; Iwagami, Yoshifumi ; Tomimaru, Yoshito ; Akita, Hirofumi ; Asaoka, Tadafumi ; Noda, Takehiro ; Takeda, Yutaka ; Tanemura, Masahiro ; Mori, Masaki ; Doki, Yuichiro. / Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma. In: Annals of Surgical Oncology. 2019.
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abstract = "Background: CD36, a multi-ligand scavenger receptor, has been associated with several cancers. Many studies have revealed that CD36 contributed to cancer malignancy. This study aimed to reveal the function of CD36 expression in pancreatic ductal adenocarcinoma (PDAC). Methods: CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with PDAC. We divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. Gemcitabine-resistant (GR) PDAC cell lines were transfected with small interfering RNA (siRNA) that specifically targeted CD36 to evaluate chemoresistance and apoptosis. Results: In resected PDAC samples, CD36 expression was significantly correlated with microinvasion into the venous system (p = 0.0284). Patients with high CD36 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates than patients with low expression; thus, CD36 was an independent prognostic factor for OS and RFS. In subgroup analyses, CD36 was an independent risk factor for OS and RFS in 59 patients treated with gemcitabine adjuvant chemotherapy. CD36 expression was upregulated in PDAC–GR cell lines compared with the PDAC parent cell line. Transduction with siRNA downregulated CD36, which reduced PDAC cell resistance to gemcitabine and inhibited anti-apoptosis proteins. Conclusion: CD36 expression influenced gemcitabine resistance by regulating anti-apoptosis proteins. High CD36 expression was a significant, unfavorable prognostic factor in PDAC. Anti-CD36 treatment might serve as an optional treatment for lowering resistance to gemcitabine.",
author = "Masahiko Kubo and Kunihito Gotoh and Hidetoshi Eguchi and Shogo Kobayashi and Yoshifumi Iwagami and Yoshito Tomimaru and Hirofumi Akita and Tadafumi Asaoka and Takehiro Noda and Yutaka Takeda and Masahiro Tanemura and Masaki Mori and Yuichiro Doki",
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AU - Kubo, Masahiko

AU - Gotoh, Kunihito

AU - Eguchi, Hidetoshi

AU - Kobayashi, Shogo

AU - Iwagami, Yoshifumi

AU - Tomimaru, Yoshito

AU - Akita, Hirofumi

AU - Asaoka, Tadafumi

AU - Noda, Takehiro

AU - Takeda, Yutaka

AU - Tanemura, Masahiro

AU - Mori, Masaki

AU - Doki, Yuichiro

PY - 2019/1/1

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N2 - Background: CD36, a multi-ligand scavenger receptor, has been associated with several cancers. Many studies have revealed that CD36 contributed to cancer malignancy. This study aimed to reveal the function of CD36 expression in pancreatic ductal adenocarcinoma (PDAC). Methods: CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with PDAC. We divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. Gemcitabine-resistant (GR) PDAC cell lines were transfected with small interfering RNA (siRNA) that specifically targeted CD36 to evaluate chemoresistance and apoptosis. Results: In resected PDAC samples, CD36 expression was significantly correlated with microinvasion into the venous system (p = 0.0284). Patients with high CD36 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates than patients with low expression; thus, CD36 was an independent prognostic factor for OS and RFS. In subgroup analyses, CD36 was an independent risk factor for OS and RFS in 59 patients treated with gemcitabine adjuvant chemotherapy. CD36 expression was upregulated in PDAC–GR cell lines compared with the PDAC parent cell line. Transduction with siRNA downregulated CD36, which reduced PDAC cell resistance to gemcitabine and inhibited anti-apoptosis proteins. Conclusion: CD36 expression influenced gemcitabine resistance by regulating anti-apoptosis proteins. High CD36 expression was a significant, unfavorable prognostic factor in PDAC. Anti-CD36 treatment might serve as an optional treatment for lowering resistance to gemcitabine.

AB - Background: CD36, a multi-ligand scavenger receptor, has been associated with several cancers. Many studies have revealed that CD36 contributed to cancer malignancy. This study aimed to reveal the function of CD36 expression in pancreatic ductal adenocarcinoma (PDAC). Methods: CD36 expression was characterized using immunohistochemistry in 95 clinical specimens resected from patients with PDAC. We divided patients into two groups, with different CD36 expression levels, and analyzed and compared their prognoses. CD36 expression was also assessed in PDAC cell lines. Gemcitabine-resistant (GR) PDAC cell lines were transfected with small interfering RNA (siRNA) that specifically targeted CD36 to evaluate chemoresistance and apoptosis. Results: In resected PDAC samples, CD36 expression was significantly correlated with microinvasion into the venous system (p = 0.0284). Patients with high CD36 expression had significantly lower overall survival (OS) and recurrence-free survival (RFS) rates than patients with low expression; thus, CD36 was an independent prognostic factor for OS and RFS. In subgroup analyses, CD36 was an independent risk factor for OS and RFS in 59 patients treated with gemcitabine adjuvant chemotherapy. CD36 expression was upregulated in PDAC–GR cell lines compared with the PDAC parent cell line. Transduction with siRNA downregulated CD36, which reduced PDAC cell resistance to gemcitabine and inhibited anti-apoptosis proteins. Conclusion: CD36 expression influenced gemcitabine resistance by regulating anti-apoptosis proteins. High CD36 expression was a significant, unfavorable prognostic factor in PDAC. Anti-CD36 treatment might serve as an optional treatment for lowering resistance to gemcitabine.

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