Early Screening of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis of Nanoscale Chromatin Modifications

Authors

Andrew Chang
Sravya Prabhala
Ali Daneshkhah
Jianan Lin
Hariharan Subramanian
Hemant Kumar Roy
Vadim Backman

Publication Date

4-2-2024

Journal

Scientific Reports

DOI

10.1038/s41598-024-58016-8

PMID

38565871

PMCID

PMC10987630

PubMedCentral® Posted Date

4-2-2024

Published Open-Access

no

Keywords

Humans, Artificial Intelligence, Early Detection of Cancer, Carcinogenesis, Colonoscopy, Chromatin, Biomarkers, Colorectal Neoplasms, Adenoma, Biomedical engineering, Biophysics, Biotechnology, Cancer, Structural biology, Biomarkers, Diseases, Health care, Medical research, Risk factors, Optics and photonics

Abstract

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p < 0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2 = 0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. artificial intelligence-enhanced csPWS improved diagnostic performance with AUC = 0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.

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