Non-endoscopic Method to Detect Esophageal Cancer Promising

NEW YORK (Reuters Health) – Esophageal squamous-cell carcinoma (ESCC) can be detected by analyzing a panel of methylated DNA biomarkers in cytologic samples obtained via a swallowable sponge-capsule device, researchers have found.

This approach might be particularly useful in resource-poor settings where endoscopy is not available, they say in a report in Gastroenterology.

ESCC makes up 90% of esophageal cancers globally. It can be diagnosed using esophagogastroduodenoscopy (EGD) with biopsy, but EGD is not widely available in developing countries.

“Inexpensive, safe, accessible diagnostic alternatives will likely improve diagnosis and outcome,” write Dr. Stephen J. Meltzer of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues.

They tested sponge-based sampling with a predictive biomarker panel as an ESCC screening method for developing countries.

In paired samples of ESCC tumor tissue and normal tissue, they identified five biomarkers (cg20655070, SLC35F1, TAC1, ZNF132, and ZNF542) that were hypermethylated in ESCC tumor tissue.

In cytologic samples obtained by swallowing the sponge-capsule device, these five biomarkers all exhibited significantly higher methylation levels in patients with ESCC than controls.

In a training set, age coupled with a three-biomarker algorithm (cg20655070, SLC35F1, ZNF132) proved highly accurate in detecting ESCC, with an AUC of 0.94.

In a separate test set, the algorithm successfully classified 90% of patients with ESCC, with a specificity of 0.87 and a sensitivity of 0.92, with only two false-positives and one false-negative, and a positive-predictive value (PPV) of 0.86 and negative predictive value (NPV) of 0.93.

“Notably,” the model was particularly accurate in early-stage ESCC, Dr. Meltzer and colleagues report.

“Thus, we present a systematic application of a stepwise approach to identify and validate discriminatory methylation-specific biomarkers for diagnosing ESCC in patient samples obtained using a minimally-invasive, non-endoscopic strategy,” they write.

“This method and model, with potential generalizability to the at-risk population, meet a potential ESCC screening need, since EGD is not widely available in ESCC-prone countries. Application of this screening strategy may ultimately improve early ESCC diagnosis, therapeutic intervention, and survival,” they add.

In line with prior studies, there were no adverse events from swallowing the sponge-capsule device, “illustrating its safety, convenience, ease, and efficacy,” they say.

“This strategy represents a low-risk, cost-effective esophageal sampling and diagnostic strategy that merits further study in larger prospective high-risk population screening trials,” they conclude.

The study did not have commercial funding. Dr. Meltzer is a founder of and holds equity in Capsulomics, Inc.

SOURCE: Gastroenterology, online April 26, 2022.

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