A cohort study of sex differences and prognostic biomarkers in colorectal cancer

摘要: Colorectal cancer (CRC) is one of the most common forms worldwide, with an annual incidence more than 1 million cases. Despite advancements in management CRC, mortality remains high. Accumulating evidence indicates that CRC a heterogeneous disease, which affects outcome beyond what can be predicted by disease stage and other conventional prognostic factors. Thus, there great need to identify new biomarkers enable accurate prognostication, help select patients for adjuvant treatment. The aim this thesis was investigate associations series putative survival, treatment response clinicopathological factors large cohort incident special attention sex differences. study group consisted tumours from 557 cases Malmo Diet Cancer Study (MDCS). tumours, assembled tissue microarrays, were evaluated expression cyclin D1, mismatch repair proteins, beta-catenin epidermal growth factor receptor (EGFR) immunohistochemistry, further, EGFR gene copy number (GCN) alterations brightfield double-in situ hybridization. In addition, KRAS BRAF mutational status assessed pyrosequencing. Associations investigative explored Chi Square Spearman’s correlation tests, Kaplan-Meier analysis Cox proportional hazards modelling applied survival analysis. We hereby found nuclear D1 associated female favorable prognosis, although not independently, male, but female, CRC. Microsatellite instability (MSI) correlated distinctive features, expression, independently good prognosis III-IV Moreover, overexpression prolonged microsatellite stable (MSS) tumours. also observed codon 13 mutation poor established mutations mutually exclusive, MSS MSI, respectively. reduced male Furthermore, both protein GCN latter, however, significantly alterations, substantial proportion expressing displayed normal GCN, vice versa. Finally, curatively treated receiving oxaliplatin. conclusion, results demonstrate several relevant differences correlates significance some observed. (Less)