Low CPEB1 levels may predict the benefit of 5-fluorouracil treatment in patients with colon or stomach adenocarcinoma

Jing-Zhu Cao; Dan-Dan Niu; Zhi-Ping Huang; Yong-Gang Hong; Zhen-Guang Wang; Le Yang; Bo-Lun Zhao; Guang-Lei Qiao; Liu Ouyang

doi:10.21037/jgo-22-561

Low CPEB1 levels may predict the benefit of 5-fluorouracil treatment in patients with colon or stomach adenocarcinoma

J Gastrointest Oncol. 2022 Aug;13(4):1761-1771. doi: 10.21037/jgo-22-561.

Authors

Jing-Zhu Cao^#¹, Dan-Dan Niu^#², Zhi-Ping Huang^#³, Yong-Gang Hong^#⁴, Zhen-Guang Wang⁵, Le Yang⁵, Bo-Lun Zhao⁶, Guang-Lei Qiao⁷, Liu Ouyang⁸

Affiliations

¹ Department of Endocrinology and Metabolism, Changhai Hospital, Naval Medical University, Shanghai, China.
² Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China.
³ Department of Hepatobiliary Surgery, General Hospital of Southern Theatre Command, Guangzhou, China.
⁴ Department of Colorectal Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
⁵ The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
⁶ School of Nursing, Dalian University, Dalian, China.
⁷ Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁸ Department of the HBP Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.

^# Contributed equally.

Abstract

Background: 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.

Methods: The expression of CPEB1 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 CPEB1 on the migration and invasion abilities of gastric cancer (GC) and CRC cells.

Results: The expression levels of CPEB1 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 (MMP)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 m⁶A demethylation of CPEB1 mRNA.

Conclusions: 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.

Keywords: 5-fluorouracil treatment (5-FU treatment); Cytoplasmic polyadenylation element-binding protein 1 (CPEB1); biomarker; colon adenocarcinoma; stomach adenocarcinoma.