Roel Bogie

Chapter 10

Molecular feature analysis

Biological PCCRCs vs DCRCs Mutation P value

OR [95% CI]

APC

0.889 0.487

0.96 [0.47 , 1.92] 1.41 [0.53 , 3.74] 1.08 [0.38 , 3.10] 0.82 [0.36 , 1.86] 0.83 [0.37 , 1.84] 1.01 [0.41 , 2.51] 1.67 [0.59 , 4.71] 0.65 [0.20 , 2.11] 0.71 [0.35 , 1.44] 0.36 [0.18 , 0.73] 1.01 [0.51 , 2.01] 0.49 [0.25 , 0.96] 1.69 [0.68 , 4.16] 1.44 [0.75 , 2.75]

BRAF

FBXW7

0.88

KIT

0.625 0.636 0.984 0.329 0.468 0.344 0.005 0.969 0.038 0.254 0.267

KRAS

PIC3CA

PTEN

SMAD4

TP53

18q loss 17p loss 13q gain

MSI

CIMP high

OR: Biological PCCRCs vs detected CRCs 4 3 2 1 0

Molecular features of biological PCCRCs only versus DCRCs When comparing the 94 PCCRCs caused by biological factors to the DCRCs, next to the loss of 18q chromosome, the gain of the 13q chromosome and loss of a small segment of the 17p chromosome (1 MB size), were also significantly less often present in PCCRCs compared to DCRCs in univariate analysis ( Table 10.4 ). MSI and high CIMP remained significantly more prevalent in PCCRCs. In the 48 gene panel, significantly more BRAF was present in PCCRCs compared to DCRCs ( P =0.049 and P =0.031, respectively). After correction for age, gender and tumor location in a logistic regression model, of the above-mentioned differences, only 18q loss and 13q gain remained significantly different. All other molecular characteristics between PCCRCs and DCRCs were comparable ( Figure 10.2b ). Clustering analysis considering all molecular features Interaction between the molecular features was not tested in the logistic regression models because of limited power. Hierarchical clustering was used to show whether certain molecular features correlated. The prevalence of each CRC type within the identified clusters was tested afterwards. Figure 10.2b: Comparison of molecular features between post-colonoscopy colorectal cancers (PCCRCs) and detected colorectal cancers (DCRCs). | Forest plots showing the associations of several molecular features of PCCRCs with plausible biological etiology compared to DCRCs, after multiple imputation of missing values and correction for age, gender, and tumor location. OR, Odds Ratio; CI, confidence interval.

194