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

摘要: Colorectal cancer is the third most common and fourth lethal in world. In majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining high mortality. The standard treatment for with locally non-metastatic rectal neoadjuvant radio-chemotherapy (NRCT) 5-fluorouracil (5-FU) followed by surgery, but resistance rate to this remains approximately 30% non-responders. lack evidence available clinical practice predict NRCT 5-FU guide therefore encourages search biomarkers resistance. From twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before patients, we extracted analysed tumor proteome these patients. data, were able classify our cohort into three response groups: non-responders (NR), partial responders (PR) total (TR), compare proteomes different groups. We have highlighted 384 differentially abundant proteins between NR PR, 248 TR 417 PR TR. Among proteins, identified many as having a role (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: NR). also that DPYD, main degradation enzyme 5-FU, was NR, well several ribosomal mitochondrial NR. Data via ProteomeXchange identifier PXD008440. retrospective study, implemented protein extraction protocol from FFPE biopsy highlight differences groups RCTN cancer. These results will pave way larger better sensitivity specificity signature decisions choice treatment.