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Upregulated OCT3 has the potential to improve the survival of colorectal cancer patients treated with (m)FOLFOX6 adjuvant chemotherapy

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

To investigate the influence of organic cation transporter 3 (OCT3) expression on the effect of the combination regimen of 5-fluorouracil, folinic acid and oxaliplatin ((m)FOLFOX6) in colorectal cancer (CRC) patients.

Methods

This is a retrospective study conducted at a single centre (Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, China). Patients with stage IIb-IV resectable CRC who were being postoperatively treated with (m)FOLFOX6 as a first-line adjuvant chemotherapy regimen for at least 5 cycles and had resected primary tumour samples available were eligible for the study. Patients who preoperatively received chemotherapy and/or radiotherapy or were treated with targeted drugs or other anticancer drugs were excluded from the study. Immunohistochemical staining and digital image analysis were used to assess OCT3 expression in tumour samples. According to OCT3 expression level, the receiver operating characteristic curve (ROC curve) was used to divide the patients into two groups. Cox proportional risk regression was performed with the forward LR (forward stepwise regression based on maximum likelihood estimation) method using SPSS17.0 software. The primary endpoint was the 2-year progression-free survival.

Results

In total, 57 patients were included between 2014 and 2016 according to the inclusion and exclusion criteria (22 had low OCT3 expression, and 35 had high OCT3 expression). The mean age was 55.7 (30–74) years, and 37 of the total patients were male. According to TNM stage, 5 patients had stage IV disease, 44 patients had stage III disease, and 8 patients had stage II disease. Through Cox regression analysis, we found that among patients receiving the (m)FOLFOX6 regimen, those with higher OCT3 expression had a higher two-year progression-free survival rate than those with lower OCT3 expression (P = 0.038). The hazard ratio of patients with high OCT3 expression compared with patients with low OCT3 expression was 0.247. Besides, it was found that the age of patients was negatively correlated with expression level of OCT3, which can explain why patients over 70 years do not benefit from oxaliplatin-containing chemotherapy.

Conclusions

High OCT3 expression in CRC tissues may be a protective factor for CRC patients treated with (m)FOLFOX6.

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Acknowledgements

We thank to Liu Huan, Wu Xingwei for technical assistance in data collecting of patients.

Author information

Authors and Affiliations

  1. Department of pharmacy, Affiliated hospital of Zunyi Medical University, Guizhou, 563003, China

    Juan Gu

  2. Department of Clinical Pharmacy, West China School of Pharmacy, Sichuan University, No. 3, section 17, Renmin South Road, Wuhou District, Chengdu City, 610041, Sichuan, China

    Juan Gu, Enwu Long, Shiwei Tang, Suqin Feng, Ling Wang & Xuehua Jiang

  3. Department of Pathology, Sichuan academy of medical sciences, Sichuan province people’s hospital, Sichuan, 610072, China

    Dandan Dong

  4. Department of pharmacy, Sichuan academy of medical sciences, Sichuan province people’s hospital, Sichuan, 610072, China

    Enwu Long

  5. Department of pharmacy, People’s hospital of Xishuangbanna, Dai Autonomous prefecture, 666100, Yunnan, China

    Tingting Li

  6. School of Pharmacy, Zunyi Medical University, Zunyi, 563006, China

    Xuehua Jiang

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  1. Juan Gu
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Contributions

Conception and design: JG, LW, XJ. Acquisition of data: JG, EL, DD, Analysis and interpretation of data: JG, TL. Drafting the manuscript: JG, ST, SF. Final approval of the version to be published: JG, XJ. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xuehua Jiang.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the ethics committees at Sichuan academy of medical Sciences & Sichuan Provincial People’s Hospital in China. Written informed consent was not obtained from the patients or their relatives due to the retrospective study design of using the electronic health records and no additional interventions were given to the subjects.

Competing of interests

The authors have no competing interests to declare.

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Juan Gu and Dandan Dong are Co-first author

A brief description

This study explored the relationship of transporter OCT3 protein expression level in colorectal cancer tissues and the effect of oxaliplatin on colorectal cancer. The population we investigated were patients with stage IIb-IV resectable CRC who were postoperatively treated with (m)FOLFOX6 as a first-line adjuvant chemotherapy regimen. We found that the prognosis differed between patients with high OCT3 expression level and low OCT3 expression level, and the age of patients was negatively correlated with expression level of OCT3. These findings could help in implementing appropriate CRC treatment regimens.

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Gu, J., Dong, D., Long, E. et al. Upregulated OCT3 has the potential to improve the survival of colorectal cancer patients treated with (m)FOLFOX6 adjuvant chemotherapy. Int J Colorectal Dis 34, 2151–2159 (2019). https://doi.org/10.1007/s00384-019-03407-x

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