KRAS Status is Associated with Metabolic Parameters in Metastatic Colorectal Cancer According to Primary Tumour Location
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ORIGINAL ARTICLE
KRAS Status is Associated with Metabolic Parameters in Metastatic Colorectal Cancer According to Primary Tumour Location M. Tabuso 1,2
&
M. Christian 3 & P. K. Kimani 2 & K. Gopalakrishnan 4 & R. P. Arasaradnam 1,5,6,7
Received: 7 February 2020 / Accepted: 11 June 2020 # The Author(s) 2020
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 A c.34G > T c.38G > A c.35G > C c.35G > A c.38G > A
G12S G12V G12D G12C
3 (1.5) 17 (8.5) 6 (3) 8 (4)
1 (1) 8 (7.5) 3 (2.8) 4 (3.7)
2 (2) 9 (9.5) 3 (3) 4 (4)
G12A
29 (14)
17 (16)
12 (12.6)
G13D
2 (1)
–
2 (2)
c.38G > A c.37G > T c.181C > A c.183A > C c.436G > A c.436G > C c.437C > T
G13A
9 (4.5)
5 (4.7)
4 (4)
Q61K Q61H p.A146T p.A146P p.A146P
3 (1.5)
–
3 (3)
4 (2)
4 (3.7)
–
12 13 13 61 146
mCRC: metastatic colorectal cancer
recto-sigmoid cancers, thus leading to the deduction that lipid lowering treatment may be effective in such subset of mCRC patients. Clinical studies on the effectiveness of statin use after CRC diagnosis have yielded inconclusive results [25–28].A recent systematic review and meta-analysis evaluating statin use and mortality in CRC patients has highlighted that statin use pre and post CRC diagnosis improved overall and cancer specific survival in CRC patients. However, no statistical difference in all cause mortality in post-CRC diagnosis statin users in subgroup analysis by KRAS mutation status was identified,
although there was a trend towards a reduction in all cause mortality in KRAS mutated CRC patients in treatment with statins after CRC diagnosis [29]. Therefore, there is an urgent clinical need to identify an appropriate subgroup of CRC patients that would benefit from statin treatment in association with adjuvant chemotherapy. Retrospective cohort studies have shown that statin use in rectal cancer patients undergoing neoadjuvant chemoradiotherapy appears to confer higher pathological regression rates [30, 31]. Result
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