Correlating colorectal cancer risk with field carcinogenesis progression using partial wave spectroscopic microscopy

Abstract

Prior to the development of a localized cancerous tumor, diffuse molecular, and structural alterations occur throughout an organ due to genetic, environmental, and lifestyle factors. This process is known as field carcinogenesis. In this study, we used partial wave spectroscopic (PWS) microscopy to explore the progression of field carcinogenesis by measuring samples collected from 190 patients with a range of colonic history (no history, low‐risk history, and high‐risk history) and current colon health (healthy, nondiminutive adenomas (NDA; ≥5 mm and <10 mm), and advanced adenoma [AA; ≥10 mm, HGD, or >25% villous features]). The low‐risk history groups include patients with a history of NDA. The high‐risk history groups include patients with either a history of AA or colorectal cancer (CRC). PWS is a nanoscale‐sensitive imaging technique which measures the organization of intracellular structure. Previous studies have shown that PWS is sensitive to changes in the higher‐order (20–200 nm) chromatin topology that occur due to field carcinogenesis within histologically normal cells. The results of this study show that these nanoscale structural alterations are correlated with a patient's colonic history, which suggests that PWS can detect altered field carcinogenic signatures even in patients with negative colonoscopies. Furthermore, we developed a model to calculate the 5‐year risk of developing CRC for each patient group. We found that our data fit this model remarkably well (R 2 = 0.946). This correlation suggests that PWS could potentially be used to monitor CRC progression less invasively and in patients without adenomas, which opens PWS to many potential cancer care applications.

Early Upper Aerodigestive Tract Cancer Detection Using Electron Microscopy to Reveal Chromatin Packing Alterations in Buccal Mucosa Cells

“…Elevated D is a hallmark of cancer cells and has been reported through multiple lines of work using Partial-Wave Spectroscopic (PWS) microscopy in colorectal, lung, and breast cancers (Subramanian et al, 2009 a ; Gladstein et al, 2018). From a theoretical perspective, the spatial arrangement of chromatin packing affects large-scale gene expression patterns through a number of physical regulators, such as chromatin volume concentration, accessible surface area, and chromatin packing scaling D (Huang et al, 2020; Virk et al, 2020 a ).…”

<p>The Impact of Smoking on Pulmonary Metastasis in Colorectal Cancer</p>

“…In the past, some studies showed the etiologic field effect models which is the exposures and genetic factor promote tissue microenvironment of cancer and suggest that exposure may be associated with cancer progression. 24 , 25 Smoking is considered one of the exposures and it influences multiple phases of tumor evolution. Therefore, past report supported that smoking may promote microenvironment of lungs, and causes pulmonary metastases of CRC.…”

Three-Dimensional Nanoscale Nuclear Architecture Mapping of Rectal Biopsies Detects Colorectal Neoplasia in Patients with Inflammatory Bowel Disease

“…31) also detect structural changes with nanoscale sensitivity. PWS, for example, measures interference between scattering from within the cell and the strong reflection from the cell surface-with its varying surface topography-to quantify the disorder strength of cellular mass density (32), whereas CLASS models subcellular size distributions within the cell by averaging light back-scattered from within a confocal volume. Unlike these modalities, nanoNAM uses a stable and sample-independent reference signal to obtain the spectral interference signal from which it extracts 3D depth-resolved intrinsic nuclear architectural properties after mapping it to the optical space via Fourier mapping.…”