Cao Jing-Zhu, Niu Dan-Dan, Huang Zhi-Ping, Hong Yong-Gang, Wang Zhen-Guang, Yang Le, Zhao Bo-Lun, Qiao Guang-Lei, Ouyang Liu
Department of Endocrinology and Metabolism, Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China.
J Gastrointest Oncol. 2022 Aug;13(4):1761-1771. doi: 10.21037/jgo-22-561.
For patients with colon or stomach adenocarcinoma, 5-fluorouracil (5-FU) is an essential component of systemic chemotherapy in the palliative and adjuvant settings. The post-transcriptional regulatory factor cytoplasmic polyadenylation element-binding protein 1 (CPEB1) has been reported to be linked to tumor metastasis. This study aimed to investigate the relationship between CPEB1 expression and 5-FU treatment response in patients with colon and stomach adenocarcinomas.
The expression of in stomach adenocarcinoma and colorectal cancer (CRC) tissues and in cell lines was determined by quantitative real-time PCR (qRT-PCR) and immunohistochemistry analyses. Transwell assays were employed to analyze the effects of on the migration and invasion abilities of gastric cancer (GC) and CRC cells.
The expression levels of were increased in colon and stomach adenocarcinoma and were negatively correlated with malignancy and poor patient survival. Data suggested that patients with CRC or GC who had strong CPEB1 expression responded poorly to 5-FU treatment. Furthermore, knockdown of CPEB1 inhibited the migration and invasion of CRC and GC cells via a mechanism involving decreased expression of matrix metalloprotein ()2, 7, and 9. Finally, our methylated RNA immunoprecipitation PCR (meRIP qPCR) data suggested that the increased CPEB1 expression in colon and stomach adenocarcinomas might be mediated by FTO (FTO alpha-ketoglutarate dependent dioxygenase)-dependent mA demethylation of CPEB1 mRNA.
Our results indicate that the level of CPEB1 expression may be valuable for predicting the benefit of 5-FU treatment for patients with colon and stomach adenocarcinomas. We therefore propose that low CPEB1 expression may represent a novel biomarker for personalized 5-FU therapy.
对于结肠或胃腺癌患者，5-氟尿嘧啶（5-FU）是姑息和辅助治疗中全身化疗的重要组成部分。据报道，转录后调节因子细胞质聚腺苷酸化元件结合蛋白1（CPEB1）与肿瘤转移有关。本研究旨在探讨CPEB1表达与结肠和胃腺癌患者5-FU治疗反应之间的关系。
通过定量实时PCR（qRT-PCR）和免疫组织化学分析，测定胃腺癌和结直肠癌（CRC）组织及细胞系中CPEB1的表达。采用Transwell试验分析CPEB1对胃癌（GC）和CRC细胞迁移和侵袭能力的影响。
CPEB1在结肠和胃腺癌中的表达水平升高，且与恶性程度和患者预后不良呈负相关。数据表明，CPEB1表达强的CRC或GC患者对5-FU治疗反应较差。此外，敲低CPEB1通过降低基质金属蛋白酶（MMP）2、7和9的表达，抑制CRC和GC细胞的迁移和侵袭。最后，我们的甲基化RNA免疫沉淀PCR（meRIP qPCR）数据表明，结肠和胃腺癌中CPEB1表达的增加可能是由FTO（FTOα-酮戊二酸依赖性双加氧酶）依赖的CPEB1 mRNA mA去甲基化介导的。
我们的结果表明，CPEB1表达水平对于预测结肠和胃腺癌患者5-FU治疗的获益可能具有重要价值。因此，我们提出低CPEB1表达可能代表一种用于个性化5-FU治疗的新型生物标志物。
