Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma
Impact of CD36 on Chemoresistance in Pancreatic Ductal Adenocarcinoma
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DOI：
10.1245/s10434-019-07927-2
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发表时间：
2019-10-11
影响因子：
3.7
通讯作者：
Doki, Yuichiro
中科院分区：
文献类型：
--
作者：
Kubo, Masahiko;Gotoh, Kunihito;Doki, Yuichiro
CD36是一种多配体清道夫受体，与多种癌症有关。许多研究表明CD36与癌症恶性有关。本研究旨在揭示CD36在胰腺导管腺癌（pancreatic ductal adencarcinoma， PDAC）中的表达功能。方法采用免疫组化方法对95例PDAC患者临床标本进行CD36表达检测。我们将患者分为两组，CD36表达水平不同，并分析和比较其预后。CD36在PDAC细胞系中的表达也被评估。用特异性靶向CD36的小干扰RNA （siRNA）转染吉西他滨耐药（GR） PDAC细胞系，以评估化疗耐药和细胞凋亡。结果在切除的PDAC样本中，CD36表达与静脉系统微侵入有显著相关性（p = 0.0284）。CD36高表达患者的总生存期（OS）和无复发生存率（RFS）明显低于低表达患者；因此，CD36是OS和RFS的独立预后因素。在亚组分析中，CD36是59例吉西他滨辅助化疗患者OS和RFS的独立危险因素。与PDAC亲本细胞系相比，PDAC- gr细胞系中CD36表达上调。siRNA转导下调CD36，降低PDAC细胞对吉西他滨的耐药性，抑制抗凋亡蛋白。结论CD36表达通过调控抗凋亡蛋白影响吉西他滨耐药。高CD36表达是PDAC中重要的不利预后因素。抗cd36治疗可作为降低吉西他滨耐药的可选治疗。
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.