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Chauvin A, Wang CS, Geha S, et al. The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature. Clin Proteomics. 2018;15:16doi: 10.1186/s12014-018-9192-2.
Chauvin, A., Wang, C. S., Geha, S., Garde-Granger, P., Mathieu, A. A., Lacasse, V., & Boisvert, F. M. (2018). The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature. Clinical proteomics, 1516. https://doi.org/10.1186/s12014-018-9192-2
Chauvin, Anaïs, et al. "The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature." Clinical proteomics vol. 15 (2018): 16. doi: https://doi.org/10.1186/s12014-018-9192-2
Chauvin A, Wang CS, Geha S, Garde-Granger P, Mathieu AA, Lacasse V, Boisvert FM. The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature. Clin Proteomics. 2018 Apr 13;15:16. doi: 10.1186/s12014-018-9192-2. eCollection 2018. PMID: 29681787; PMCID: PMC5898006.
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Clin Proteomics. 2018 Apr 13;15:16. doi: 10.1186/s12014-018-9192-2. eCollection 2018.

The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature.

Clinical proteomics

Anaïs Chauvin, Chang-Shu Wang, Sameh Geha, Perrine Garde-Granger, Alex-Ane Mathieu, Vincent Lacasse, François-Michel Boisvert

Affiliations

  1. 1Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3201 Jean-Mignault, Sherbrooke, QC J1E 4K8 Canada.
  2. 2Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC Canada.
  3. 3Department of Pathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC Canada.

PMID: 29681787 PMCID: PMC5898006 DOI: 10.1186/s12014-018-9192-2

Abstract

BACKGROUND: Colorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders. The lack of evidence available in clinical practice to predict NRCT resistance to 5-FU and to guide clinical practice therefore encourages the search for biomarkers of this resistance.

METHODS: From twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before NRCT with 5-FU of locally advanced non-metastatic rectal cancer patients, we extracted and analysed the tumor proteome of these patients. From clinical data, we were able to classify the twenty-three patients in our cohort into three treatment response groups: non-responders (NR), partial responders (PR) and total responders (TR), and to compare the proteomes of these different groups.

RESULTS: We have highlighted 384 differentially abundant proteins between NR and PR, 248 between NR and TR and 417 between PR and TR. Among these proteins, we have identified many differentially abundant proteins identified as having a role in cancer (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed in TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: overexpressed in NR). We have also identified that DPYD, the main degradation enzyme of 5-FU, was overexpressed in NR, as well as several ribosomal and mitochondrial proteins also overexpressed in NR. Data are available via ProteomeXchange with identifier PXD008440.

CONCLUSIONS: From these retrospective study, we implemented a protein extraction protocol from FFPE biopsy to highlight protein differences between different response groups to RCTN with 5-FU in patients with locally advanced non-metastatic rectal cancer. These results will pave the way for a larger cohort for better sensitivity and specificity of the signature to guide decisions in the choice of treatment.

Keywords: 5-Fluorouracil; Mass spectrometry; Predictive biomarkers; Proteomics; Rectal cancer; Resistance to neoadjuvant radio-chemotherapy

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