Abstract
Colorectal cancer (CRC) is characterized by complex interplay between macroenvironmental factors and tumour microenvironment, leading to variable outcomes in CRC patients. To date, there is still a need to identify macroenvironment/microenvironment factors that could define subgroup of patients that would benefit from specific anti-cancer treatment in order to improve patient selection for individualized targeted-based therapy. Aim of this study was to evaluate associations between metabolic parameters and KRAS status in metastatic CRC (mCRC) according to a new tumour site classification. Retrospective data were extracted from a total of 201 patients diagnosed with mCRC between 2012 and 2017 extracted from an established CRC database at our tertiary institute. Clinical-pathological data, including age, gender, BMI, hypertension, diabetes, pre-CRC diagnosis serum lipid levels and KRAS status were recorded. Categorical characteristics were compared using chi-squared test. Continuous characteristics were compared using Mann-Whitney U test. Log rank test was used to compare hazards for survival. In all comparisons, a two-sided P value <0.05 was considered statistically significant. Out of 201 patients, 170 patients with complete serum lipid profile were included in the analysis. In recto-sigmoid cancers there was a statistically significant association between high cholesterol:high-density lipoprotein (chol:HDL) ratio and KRAS mutation (OR 2.69, 95% CI 1.1–6.4, p = 0,02). In non recto-sigmoid cancers, high cholesterol was associated with KRAS WT (OR 0.39, CI 0.15–0.97, p = 0.04). In 22 patients with KRAS mutated recto-sigmoid cancer stage IV at diagnosis normal chol:HDL ratio was associated with a trend to better survival (p = 0.06). High chol:HDL ratio was significantly associated with KRAS mutated metastatic recto-sigmoid cancers. A subgroup of mCRC patients with KRAS mutated recto-sigmoid cancer may benefit from optimal lipid lowering treatment.
Highlights
Colorectal cancer (CRC) is a heterogeneous disease characterized by complex interplay between genetic and epigenetic modifications within tumour and environmental factors
We evaluated associations between clinical, metabolic and molecular parameters (KRAS status) in metastatic CRC patients according to a novel classification for primary tumour location
In this study we investigated associations between serum lipid profile, body mass index (BMI) and metabolic factors with KRAS status according to primary tumour location
Summary
Colorectal cancer (CRC) is a heterogeneous disease characterized by complex interplay between genetic and epigenetic modifications within tumour and environmental factors. Obesity and metabolic syndrome (MetS) are established risk factors of CRC incidence and mortality [2, 3]. The role of dysfunctional adipose tissue in cancer progression has emerged [4, 5]. Interactions between genetic, epigenetic and environmental factors in CRC risk and carcinogenesis remain poorly characterized. Despite recent advances in cancer therapies, CRC remains the second cause of cancer death in the Western world [6]. There is still a need to define subgroup of patients that would benefit from specific anti-cancer treatment in order to improve patient selection for individualized targeted-based therapy
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