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Correlation between mismatch repair and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy

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Abstract

Background

Almost all adjuvant chemotherapy regimens for gastric cancer recommended by guidelines are fluorouracil (5-FU) based, and 5-FU-based adjuvant chemotherapy plays an important role in reducing the recurrence of gastric cancer after surgery. However, the effect of mismatch repair (MMR) status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer remains controversial.

Materials and methods

We prospectively included patients with gastric cancer who underwent radical gastrectomy between March 14, 2017 and September 30, 2021. The included patients received 5-FU-based adjuvant chemotherapy or surgery alone. The MMR status of patients was divided into MMR proficient (pMMR) and MMR defective (dMMR) according to four MMR proteins. Peripheral blood was collected for systemic inflammation analysis. The main purpose of this study was to analyze the effect of MMR status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer. We also analyzed the differences in systemic inflammation levels in different MMR status and their impact on survival.

Results

A total of 479 patients were enrolled, with a median follow-up period of time was 36 months. In the surgery alone group, dMMR gastric cancer had better disease-free survival (DFS) (hazard ratio [HR] = 4.33, 95% confidence interval [CI] 1.25–15.02, p = 0.02) than pMMR, and in the adjuvant chemotherapy group, there was no significant difference in DFS (HR = 1.16, 95% CI 0.65–2.07, p = 0.61) between dMMR and pMMR gastric cancer. The same results were seen for overall survival (OS). In addition, the result show that in the dMMR group, there was no difference in DFS (HR = 1.62, 95% CI 0.46–5.77, p = 0.45) between patients receiving adjuvant chemotherapy and those receiving surgery alone. In the pMMR group, the DFS values (HR = 0.59, 95%CI 0.35–0.99, p = 0.04) of patients receiving adjuvant chemotherapy were better than those of patients receiving surgery alone, and the same results were observed for OS. In addition, among pMMR patients, patients with a low platelet lymphocyte ratio (PLR) who received 5-FU adjuvant chemotherapy and those with a low neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) who received surgery alone had better DFS and OS.

Conclusion

To our knowledge, this is the first prospective study to specifically explore the correlation between MMR and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. The results showed that gastric cancer patients with pMMR can benefit from 5-FU-based adjuvant chemotherapy, but those with dMMR cannot. Among pMMR patients, lower PLR and SII values with surgery alone and lower NLRs in those receiving 5-FU-based adjuvant chemotherapy were associated with higher DFS and OS.

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Funding

This work was supported by the Project of Basic Research for application in the Science and Technology Department of Qinghai Province (2019-ZJ-7003) and Science and Technology plan project contract Qinghai Province (2020-ZJ-779).

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Authors and Affiliations

  1. Research Center for High Altitude Medicine, Key Laboratory of Plateau Medicine, Ministry of Education, Qinghai Key Laboratory of Plateau Medical Application Foundation (Qinghai-Utah Joint Research Key Laboratory for High Altitude Medicine), Qinghai University, Qinghai University, Xining, People’s Republic of China

    Fuxing Zhao & Jiuda Zhao

  2. Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, People’s Republic of China

    Fuxing Zhao, Guoshuang Shen, Dengfeng Ren, Miaozhou Wang, Yi Zhao, Zhen Liu, Qiqi Xie, Zhilin Liu, Zitao Li & Jiuda Zhao

  3. Department of Medical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, People’s Republic of China

    Fuxing Zhao, Dengfeng Ren, Jinhua Ma & Jiuda Zhao

  4. Department of Medical Oncology, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China

    Enxi Li

  5. The Fifth People’s Hospital of Qinghai Province, The First Ward of Oncology, Xining, People’s Republic of China

    Qiuxia Dong & Lihong Gao

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  1. Fuxing Zhao
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Contributions

Fuxing Zhao is the first author of this manuscript. All authors made important contributions to the work in this study, including in the presentation of concepts, the design and implementation of the research, the acquisition, analysis, and statistical analysis of data, and drafting and revision of the article. Finally, the forthcoming edition was jointly approved, the authors agreed to the submission of the article to the journal, and they agreed to be responsible for all aspects of the work.

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Correspondence to Jiuda Zhao.

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535_2023_1990_MOESM1_ESM.tif

Supplementary file1 Survival analysis of patients receiving surgery alone before and after propensity score matching. (A: Comparison of DFS between dMMR and pMMR group before PSM. B: Comparison of OS between dMMR and pMMR group before PSM. C: Comparison of DFS between dMMR and pMMR group after PSM. D: Comparison of OS between dMMR and pMMR group after PSM.) (TIF 290 KB)

Supplementary file2 (DOCX 19 KB)

Supplementary file3 (DOCX 14 KB)

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Zhao, F., Li, E., Shen, G. et al. Correlation between mismatch repair and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. J Gastroenterol 58, 622–632 (2023). https://doi.org/10.1007/s00535-023-01990-z

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