2020 Fiscal Year Final Research Report
Novel candidate factors predicting the effect of S-1 adjuvant chemotherapy of pancreatic cancer
| Project/Area Number |
18K16337
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 膵癌 / 抗癌剤感受性 / プロテオミクス / CD-DST |
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| Outline of Final Research Achievements |
The aim of this study was to discover novel biomarkers to predict chemosensitivity based on the CD-DST results.Proteomics analysis was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Candidate proteins were validated in patients with 5-FU CD-DST results via immunohistochemistry (IHC). The relationships between the candidate proteins and the effect of the adjuvant S-1 were investigated via IHC.Among the 2696 proteins extracted by LC-MS/MS, C1TC and SAHH could accurately predict the CD-DST results. Recurrence-free survival (RFS) was significantly improved in the IHC-positive group compared with the IHC-negative group in both factors. The negative group did not show a significant difference from the group that did not receive S-1. Thus C1TC and SAHH have been shown to be useful biomarkers for predicting 5-FU sensitivity as a substitute for the CD-DST in adjuvant chemotherapy for PDAC.
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| Free Research Field |
消化器外科
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌は切除後S-1による半年間の補助治療が推奨されているが，補助治療による予後改善効果が得られない症例が少なからず存在する．本研究によって得られた因子は，膵癌切除後のS-1による上乗せ効果が期待できない症例の選別に有効である可能性がある．また得られた2因子はいずれも１炭素代謝(葉酸代謝及びメチオニン代謝)に関与する因子である．本因子の欠落により，S-1の効果を発揮する上で必要とされるメチレンテトラヒドロ葉酸の合成が低下することで感受性が低下するものと考えられた．本研究結果は抗癌剤のレジメン変更についての検討や，感受性を高めるために必要なアプローチを検討する上でも有用な研究になったと考えられた．
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