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Impact of Smad4 and p53 mutations on the prognosis of patients with pancreatic ductal adenocarcinoma undergoing chemotherapy

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Abstract

Background

This prospective cohort study evaluated the feasibility of using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) samples for comprehensive mutational analysis of cancer-related genes using microtissues.

Methods

Fifty patients with suspected pancreatic cancer presenting consecutively at the Kindai University Hospital between January 2018 and January 2019 were enrolled. Cancerous tissues from EUS-FNB were obtained from each tumor and subjected to histological examination and mutational analysis. The primary endpoint was the collection rate of EUS-FNB specimens suitable for comprehensive cancer panels using deep sequencing. Clinical history and genetic variations between the disease control and progressive disease groups of patients on chemotherapy were evaluated as secondary endpoints.

Results

The collection rate of EUS-FNB specimens suitable for comprehensive cancer panels using deep sequencing was 93.6%. The cancer panel was sequenced for 25 patients with pancreatic cancer treated initially with systemic chemotherapy. Mutation in p53 and Smad4 were positively and negatively associated, respectively, with disease control at the initial evaluation. The median time to progression in 15 patients with p53 and without Smad4 mutations was 182.0 days; whereas, it was 92.5 days in other 10 patients; this difference was significant (p = 0.020).

Conclusions

Tissue samples from EUS-FNB were suitable for mutational analysis. Pancreatic cancers with p53 and without Smad4 mutations responded better to chemotherapy and had a better prognosis than those others.

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Acknowledgements

The authors thank Ms. Miyuki Kodama for secretarial support.

Funding

This work was supported by a Grant-in-Aid from the Japan Research Foundation for Clinical Pharmacology (K. Kamata), JSPS KAKENHI (Grant number 21K07184, to N. Nishida), and by a grant from the Smoking Research Foundation (to N. Nishida).

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan

    Ken Kamata, Mamoru Takenaka, Naoshi Nishida, Akane Hara, Yasuo Otsuka, Hidekazu Tanaka, Shunsuke Omoto, Kosuke Minaga, Kentaro Yamao, Tomohiro Watanabe & Masatoshi Kudo

  2. Clinical Research Center, Kindai University Hospital, Osaka-Sayama, Japan

    Yasutaka Chiba

  3. Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan

    Kazuko Sakai & Kazuto Nishio

Authors
  1. Ken Kamata
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  2. Mamoru Takenaka
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  3. Naoshi Nishida
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  4. Akane Hara
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  5. Yasuo Otsuka
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  6. Hidekazu Tanaka
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  7. Shunsuke Omoto
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  8. Kosuke Minaga
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  9. Kentaro Yamao
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  10. Yasutaka Chiba
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  11. Kazuko Sakai
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  12. Kazuto Nishio
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  13. Tomohiro Watanabe
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  14. Masatoshi Kudo
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Contributions

KK wrote and revised the manuscript, conceived, and designed the study, and performed data collection and endosonographic studies. MT critically revised the manuscript for the quality of the intellectual content. NN wrote and revised the manuscript and evaluated the results of hereditary cancer panel testing. AH, YO and HT performed data collection. SO, KM, and KY performed endosonographic studies. YC performed statistical analysis. KS and KN performed hereditary cancer panel testing. TW and MK critically revised the manuscript with respect to important intellectual content.

Corresponding author

Correspondence to Naoshi Nishida.

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Conflict of interest

The authors have no conflicts of interest to disclose.

Institutional review board

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Kindai University Faculty of Medicine (protocol code: R03-029, 13/12/2017).

Informed consent

All subjects provided informed consent to participate in the study.

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Kamata, K., Takenaka, M., Nishida, N. et al. Impact of Smad4 and p53 mutations on the prognosis of patients with pancreatic ductal adenocarcinoma undergoing chemotherapy. Int J Clin Oncol 28, 1511–1519 (2023). https://doi.org/10.1007/s10147-023-02396-w

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  • DOI: https://doi.org/10.1007/s10147-023-02396-w

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