Tabuso, Maria, Christian, M., Kimani, Peter K., Gopalakrishnan, K. and Arasaradnam, Ramesh P. (2020) KRAS Status is associated with metabolic parameters in metastatic colorectal cancer according to primary tumour location. Pathology & Oncology Research, 26 . pp. 2537-2548. doi:10.1007/s12253-020-00850-y ISSN 1219-4956.

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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.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Colon (Anatomy) -- Cancer, Metabolic syndrome, Colon (Anatomy) -- Cancer -- Tumors -- Diagnosis, Lipids
Journal or Publication Title:	Pathology & Oncology Research
Publisher:	Springer
ISSN:	1219-4956
Official Date:	October 2020
Dates:	Date Event October 2020 Published 27 June 2020 Available 11 June 2020 Accepted
Volume:	26
Page Range:	pp. 2537-2548
DOI:	10.1007/s12253-020-00850-y
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	3 July 2020
Date of first compliant Open Access:	6 July 2020

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