Tabuso M, Christian M, Kimani P K, Gopalakrishnan K, Arasaradnam R P
Department of Gastroenterology, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, UK.
Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
Pathol Oncol Res. 2020 Oct;26(4):2537-2548. doi: 10.1007/s12253-020-00850-y. Epub 2020 Jun 27.
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.
结直肠癌（CRC）的特征是宏观环境因素与肿瘤微环境之间存在复杂的相互作用，这导致CRC患者的预后各不相同。迄今为止，仍需要确定能够定义可从特定抗癌治疗中获益的患者亚组的宏观环境/微环境因素，以便改善个体化靶向治疗的患者选择。本研究的目的是根据一种新的肿瘤部位分类，评估转移性结直肠癌（mCRC）患者代谢参数与KRAS状态之间的关联。回顾性数据取自2012年至2017年间在我们三级医疗机构的一个已建立的CRC数据库中确诊为mCRC的201例患者。记录临床病理数据，包括年龄、性别、体重指数、高血压、糖尿病、CRC诊断前血清脂质水平和KRAS状态。分类特征采用卡方检验进行比较。连续特征采用曼-惠特尼U检验进行比较。对数秩检验用于比较生存风险。在所有比较中，双侧P值<0.05被认为具有统计学意义。在201例患者中，170例具有完整血清脂质谱的患者被纳入分析。在直肠乙状结肠癌中，高胆固醇：高密度脂蛋白（chol:HDL）比值与KRAS突变之间存在统计学显著关联（比值比2.69，95%置信区间1.1-6.4，p = 0.02）。在非直肠乙状结肠癌中，高胆固醇与KRAS野生型相关（比值比0.39，置信区间0.15-0.97，p = 0.04）。在22例诊断时为KRAS突变的直肠乙状结肠癌IV期患者中，正常的chol:HDL比值与更好的生存趋势相关（p = 0.06）。高chol:HDL比值与KRAS突变的转移性直肠乙状结肠癌显著相关。KRAS突变的直肠乙状结肠癌mCRC患者亚组可能从最佳降脂治疗中获益。
