Sara Ribeirinho-Soares1,2, Diana Pádua1,2, Ana Luísa Amaral1,2, Elvia Valentini1,2, Daniela Azevedo3, Cristiana Marques3, Rita Barros1,2,4, Filipa Macedo5, Patrícia Mesquita1,2, Raquel Almeida6,7,8,9. 1. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal. 2. IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal. 3. Centro Hospitalar de São João, Porto, Portugal. 4. Faculty of Medicine, University of Porto, Porto, Portugal. 5. IPO-C - Instituto Português de Oncologia de Coimbra Francisco Gentil, E. P. E, Coimbra, Portugal. 6. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal. ralmeida@ipatimup.pt. 7. IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal. ralmeida@ipatimup.pt. 8. Faculty of Medicine, University of Porto, Porto, Portugal. ralmeida@ipatimup.pt. 9. Biology Department, Faculty of Sciences of the University of Porto, Porto, Portugal. ralmeida@ipatimup.pt.
Abstract
BACKGROUND: Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. METHODS: For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. RESULTS: In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. CONCLUSION: In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.
BACKGROUND:Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRCpatients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. METHODS: For this purpose, we used a one-hospital series of 227 stage II CRCpatient samples to assess the biomarker potential of the immunohistochemical expression of MUC2mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. RESULTS: In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. CONCLUSION: In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRCpatients.
Entities:
Keywords:
Biomarkers; CDX2; MUC2; SOX2; Stage II colorectal cancer
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