Gene Expression in Barrett's Esophagus Cell Lines Resemble Esophageal Squamous Cell Carcinoma Instead of Esophageal Adenocarcinoma

Anshuman Panda; Gyan Bhanot; Shridar Ganesan; Manisha Bajpai

doi:10.3390/cancers13235971

Gene Expression in Barrett's Esophagus Cell Lines Resemble Esophageal Squamous Cell Carcinoma Instead of Esophageal Adenocarcinoma

Cancers (Basel). 2021 Nov 27;13(23):5971. doi: 10.3390/cancers13235971.

Authors

Anshuman Panda¹, Gyan Bhanot^{2

3

4}, Shridar Ganesan^{1

2

5}, Manisha Bajpai^{6

7}

Affiliations

¹ Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
² Center for Systems and Computational Biology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
³ Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
⁴ Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854, USA.
⁵ Department of Medicine-Medical Oncology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
⁶ Department of Medicine-Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
⁷ Cancer Pharmacology Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

Abstract

Esophageal adenocarcinoma (EAC) is strongly associated with Barrett's esophagus (BE), a pre-malignant condition resulting from gastric reflux. Esophageal squamous cell carcinoma (ESCC), the other major subtype of esophageal cancer, shows strong association with smoking and alcohol intake and no association with gastric reflux. In this study, we constructed and validated gene expression signatures of EAC vs. ESCC tumors using publicly available datasets, and subsequently assessed the enrichment levels of these signatures in commonly used EAC and ESCC cell lines, normal esophageal tissues and normal esophageal cell lines, and primary BE tissues and BE cell lines. We found that unlike ESCC cell lines which were quite similar to primary ESCC tumors, EAC cell lines were considerably different from primary EAC tumors but still more similar to EAC tumors than ESCC tumors, as the genes up in EAC vs. ESCC (EAC^hi) had considerably lower expression in EAC cell lines than EAC tumors. However, more surprisingly, unlike various normal cell lines (EPC2, Het-1A) which were very similar to various tissues from normal esophagus, BE cell lines (BAR-T, CP-A) were extremely different from primary BE tissues, as BE cell lines had substantially lower levels of EAC^hi and substantially higher levels of ESCC^hi gene expression. This ESCC-like profile of the BAR-T remained unaltered even after prolonged exposure to an acidic bile mixture in vitro resulting in malignant transformation of this cell line. However, primary BE tissues had EAC-like gene expression profiles as expected. Only one EAC case from the Cancer Genome Atlas resembled BE cell lines, and while it had the clinical profile and some mutational features of EAC, it had some mutational features, the copy number alteration profile, and the gene expression profile of ESCC instead. These incomprehensible changes in gene expression patterns may result in ambiguous changes in the phenotype and warrants careful evaluation to inform selection of appropriate in vitro tools for future studies on esophageal adenocarcinoma.

Keywords: BAR-T; Barrett’s esophagus; esophageal adenocarcinoma; esophageal squamous cell carcinoma; gene expression signature.

Abstract

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