Prediction of adjuvant chemotherapy response in triple negative breast cancer with discovery and targeted proteomics

利用发现和靶向蛋白质组学预测三阴性乳腺癌辅助化疗反应

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作者:Angelo Gámez-Pozo, Lucía Trilla-Fuertes, Guillermo Prado-Vázquez, Cristina Chiva, Rocío López-Vacas, Paolo Nanni, Julia Berges-Soria, Jonas Grossmann, Mariana Díaz-Almirón, Eva Ciruelos, Eduard Sabidó, Enrique Espinosa, Juan Ángel Fresno Vara

Background

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and usually requires the administration of adjuvant chemotherapy after surgery but even with this treatment many patients still suffer from a relapse. The main

Conclusions

This study identified a protein combination signature that complements histopathological prognostic factors in TNBC treated with adjuvant chemotherapy. The protein signature can be used in paraffin-embedded samples, and after a prospective validation in independent series, it could be used as predictive clinical test in order to recommend participation in clinical trials or a more exhaustive follow-up.

Methods

We analyzed the proteome of a retrospective series of formalin-fixed, paraffin-embedded TNBC tissue applying high-throughput label-free quantitative proteomics. We identified several protein signatures with predictive value, which were validated with quantitative targeted proteomics in an independent cohort of patients and further evaluated in publicly available transcriptomics data.

Results

Using univariate Cox analysis, a panel of 18 proteins was significantly associated with distant metastasis-free survival of patients (p<0.01). A reduced 5-protein profile with prognostic value was identified and its prediction performance was assessed in an independent targeted proteomics experiment and a publicly available transcriptomics dataset. Predictor P5 including peptides from proteins RAC2, RAB6A, BIEA and IPYR was the best performance protein combination in predicting relapse after adjuvant chemotherapy in TNBC patients. Conclusions: This study identified a protein combination signature that complements histopathological prognostic factors in TNBC treated with adjuvant chemotherapy. The protein signature can be used in paraffin-embedded samples, and after a prospective validation in independent series, it could be used as predictive clinical test in order to recommend participation in clinical trials or a more exhaustive follow-up.

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