Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers

Sep 24, 2026

Esophageal cancer (EC) has a 92% annual mortality rate per incidence and includes esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), with EAC showing particularly poor prognosis. Limited screening and minimal molecular analysis lead to late presentation and survival under 20%. Current diagnosis relies on invasive endoscopic biopsy and histopathology. This review evaluates cellular and molecular biomarkers and specimen-retrieval strategies, emphasizing non-invasive options such as liquid biopsy using blood, urine, and saliva.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Introduction

Major EC types and epidemiology

Risk factors and disease pathogenesis

Early detection strategies and screening challenges

Treatment approaches for early and advanced EC

Review Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers Vikrant Rai 1, Joe Abdo 2,3 and Devendra K. Agrawal 1, * Citation: Rai, V.; Abdo, J.; Agrawal, D.K. Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers. Int. J. Mol. Sci. 2023, 24, 3316. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms24043316](10.3390/ijms24043316) Academic Editors: Hidekazu Suzuki, Paramjit S. Tappia and Bram Ramjiawan Received: 9 January 2023 Revised: 31 January 2023 Accepted: 6 February 2023 Published: 7 February 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA 91766, USA 2 Department of Research and Development, Stella Diagnostics, Inc., Salt Lake City, UT 84104, USA 3 ProPhase Labs, Inc., Garden City, NY 11530, USA * Correspondence: [dagrawal@westernu.edu](dagrawal@westernu.edu); Tel.: +1-909-469-7040; Fax: +1-909-469-5577 Abstract: Esophageal cancer (EC) is the deadliest cancer worldwide, with a 92% annual mortality rate per incidence. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of ECs, with EAC having one of the worst prognoses in oncology. Limited screening techniques and a lack of molecular analysis of diseased tissues have led to late-stage presentation and very low survival durations. The ﬁve-year survival rate of EC is less than 20% . Thus, early diagnosis of EC may prolong survival and improve clinical outcomes. Cellular and molecular biomarkers are used for diagnosis. At present, esophageal biopsy during upper endoscopy and histopathological analysis is the standard screening modality for both ESCC and EAC. However, this is an invasive method that fails to yield a molecular proﬁle of the diseased compartment. To decrease the invasiveness of the procedures for diagnosis, researchers are proposing non-invasive biomarkers for early diagnosis and point-of-care screening options. Liquid biopsy involves the collection of body ﬂuids (blood, urine, and saliva) non-invasively or with minimal invasiveness. In this review, we have critically discussed various biomarkers and specimen retrieval techniques for ESCC and EAC. Keywords: esophageal carcinoma; esophageal adenocarcinoma; biomarkers; blood; urine; saliva 1. Introduction Its poor prognosis and high mortality rate make esophageal cancer (EC) one of the deadliest cancers worldwide. EC is the eighth most common cancer worldwide (the seventh most common cancer in men and the thirteenth most common cancer in women) and the sixth leading cause of cancer-related deaths. The two most common histological types of EC, namely esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), account for more than 90% of ECs. The ﬁve-year survival rate of EC is less than 20%[1–4] . A recent retrospective study reporting 23,804 EAC cases and 13,919 ESCC cases suggests an increasing incidence of EAC and a decreasing incidence of ESCC in the United States [3] . ESCC is characterized by the conversion of the normal squamous esophageal epithelium to ESCC via basal cell hyperplasia, dysplasia, and invasiveness. ESCC may involve any part of the esophagus (20% upper, 50% middle, and 30% lower esophagus) . Alcohol and tobacco consumption, the most common risk factors, cause cellular DNA damage and contribute to ESCC. EAC occurring in the distal esophagus occurs due to a cascade progressing from gastroesophageal reﬂux disease (GERD) to Barrett's esophagus (BE), followed by EAC with columnar metaplasia playing a cr

FAQs

Why are biomarkers important for esophageal cancer care?

Biomarkers can support early diagnosis and improve clinical outcomes by enabling molecular profiling rather than relying solely on invasive histopathological assessment.

What are the two major histological types of esophageal cancer discussed?

The review focuses on esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), which together account for more than 90% of esophageal cancers.

What non-invasive screening approach is highlighted as a promising option?

Liquid biopsy is emphasized, using body fluids such as blood, urine, and saliva to enable non-invasive or minimally invasive biomarker collection.

Sep 24, 2026

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