Proteins in stool as biomarkers for non-invasive detection of colorectal adenomas with high risk of progression
Menée à partir d'échantillons de selles collectés auprès de 129 témoins et 151 patients présentant un adénome ou un cancer colorectal, puis menée à partir de l'analyse génomique d'échantillons tissulaires d'adénome, cette étude identifie des biomarqueurs moléculaires permettant de détecter précocement un adénome à haut risque de progression maligne
Screening to detect colorectal cancer (CRC) in an early or premalignant state is an effective method to reduce CRC mortality rates. Current stool‐based screening tests, e.g. fecal immunochemical test (FIT), have a suboptimal sensitivity for colorectal adenomas and difficulty distinguishing adenomas at high risk of progressing to cancer from those at lower risk. We aimed to identify stool protein biomarker panels that can be used for the early detection of high‐risk adenomas and CRC.
Proteomics data (LC–MS/MS) were collected on stool samples from adenoma (n = 71) and CRC patients (n = 81) as well as controls (n = 129). Colorectal adenoma tissue samples were characterized by low-coverage whole genome sequencing to determine their risk of progression based on specific DNA copy number changes. Proteomics data was used for logistic regression modelling to establish protein biomarker panels.
In total, 15 of the adenomas (15.8%) were defined as high-risk of progressing to cancer. A protein panel, consisting of haptoglobin (Hp), LAMP1, SYNE2 and ANXA6, was identified for the detection of high‐risk adenomas (sensitivity of 53% at specificity of 95%). Two panels, one consisting of Hp and LRG1 and one of Hp, LRG1, RBP4 and FN1 were identified for high‐risk adenomas and CRCs detection (sensitivity of 66 and 62%, respectively, at specificity of 95%). Validation of Hp as biomarker for high‐risk adenomas and CRCs was performed using an antibody‐based assay in FIT samples from a subset of individuals from the discovery series (n = 158) and an independent validation series (n = 795). Hp protein was significantly more abundant in high‐risk adenoma FIT samples compared to controls in the discovery (p-value = 0.036) and the validation series (p-value = 9e-5).
We conclude that Hp, LAMP1, SYNE2, LRG1, RBP4, FN1 and ANXA6 may be of value as stool biomarkers for early detection of high‐risk adenomas and CRCs.
The Journal of Pathology , résumé, 2019