ASSOCIATION OF FUSOBACTERIUM NUCLEATUM WITH CETUXIMAB-TREATED COLORECTAL CANCER PATIENTS

Background: Recent studies suggest that the presence of Fusobacterium nucleatum (Fn) is involved not only in the development and progression of colorectal cancer (CRC), but can also modify the response to therapy. Cetuximab, an anti-EGFR agent is one of the most important target therapies treatment of CRC patients. Aim: To investigate the presence of Fn in advanced CRC patients treated with cetuximab and associate it with patients’ survival. Materials and Methods: Retrospective study with 119 CRC patients treated with cetuximab from Barretos Cancer Hospital. The droplet digital PCR technique (ddPCR) was optimized to detect Fn DNA in samples obtained from formalin-fixed and paraffin-embedded (FFPE) tumor tissue. Results: The methodology used was able to detect less than 0.0001 nanograms of Fn DNA. The presence of bacterial DNA was observed in 35/119 cases (29,4%), with a median number of 38 bacterial DNA copies. Fn expression was further categorized in two groups: a positive, with Fn above the median bacterial DNA copies; and a negative, including Fn below median bacterial DNA copies and absence of bacterial DNA. Patients Fn positive were associated with disease progression on tumor response to cetuximab treatment when compared with Fn negative (p-value= 0.049). There was no association of Fn presence and patient overall survival evaluated, with a mean of 15 months for Fn negative vs 11 months for Fn positive cases (p-value= 0.263). Conclusion: ddPCR is a specific and sensitive technique for Fn DNA detection in FFPE. Fusobacterium nucleatum is present in 1/3 of cases, and despite the lack of association with patient overall survival it is associate with disease progression on tumor response to cetuximab treatment and it can constitute an additional biomarker of CRC therapy.