Trauma/Burns
MicroRNA expression profiles in the esophagus of children with caustic stenosis: A pathway towards esophageal cancer?

https://doi.org/10.1016/j.jpedsurg.2020.02.009Get rights and content

Abstract

Background

Eighty percent of caustic ingestions occur in children and esophageal neoplasms may develop as a late complication of such injury. The identification of biomarkers is a promising strategy to improve early diagnosis of esophageal cancer or caustic lesions that are at an increased risk of progression.

Study design/aims

This study aimed at identifying global microRNA (miRNA) expression changes in esophageal mucosa from children with caustic stenosis. The study included 27 biopsy samples from 15 patients. Samples were divided into two groups, according to the time elapsed after injury (N = 15 in Group A, with less than five years of follow-up and N = 12 in Group B, with more than five years of follow-up). miRNA expression profiles were determined in each lesion, compared with normal esophageal tissues from control group. We used the TaqMan Human MicroRNA Arrays (Thermo Fisher) platform. Furthermore, bioinformatic algorithms were used to identify miRNA target genes and biological pathways including miRNAs and their target genes potentially associated with esophageal disease.

Results

Thirteen miRNAs were significantly deregulated (9 over- and 4 underexpressed) in patients from Group A. In patients from Group B, two miRNAs were over- and two were underexpressed. Of note, miR-374 and miR-574 were deregulated in Group B patients and have been linked to esophageal tumorigenesis. We identified signal transduction and transcription factor networks with genes strongly related to development and progression of esophageal cancer.

Conclusion

miRNAs identified here contribute to a better understanding of pathways associated with malignant transformation from caustic stenosis to neoplastic lesions. This study may serve as a basis for validation of miRNAs, including miR-374 and miR-574, as potential biomarkers of early cancer detection.

Section snippets

Ethics statement

This study was performed in accordance with the ethical standards of the Declaration of Helsinki and according to national and international guidelines. Our study has been approved by the Research Ethics Boards of the Faculty of Medicine (FMB), UNESP, Botucatu, SP (REB #1089452/2015).

Patient samples

Patients who met inclusion criteria were those who were less than 15 years of age and with a history of hospital admission owing to an esophageal lesion induced by caustic ingestion, who have been subjected to

Patient demographic and clinical data

We analyzed 27 biopsies from 15 patients with esophageal caustic lesions. These samples were divided into two groups, 15 in Group A (less than five years of follow-up since injury) and 12 in Group B (more than five years of follow-up since injury). Given that patient follow-up was > 17 years, some of them have samples included in both groups. Demographic data and information on clinical features are shown in Table 1.

Deregulated miRNA expression in esophageal samples exposed to caustic ingestion

miRNA expression analysis of Group A cases showed that 13 significantly

Discussion

Changes in miRNA expression are known to contribute to cancer development and progression, with different miRNA expression profiles associated with distinct biological tumor behavior [33]. The pathophysiologic mechanism of esophageal cancer related to caustic ingestion is not well understood [11]. Pathological findings have shown that the epithelium overlying an injured area is vulnerable to neoplastic transformation, especially if subjected to chemical, physical, or thermal aggression for

Conclusions

miRNAs identified here may be associated with malignant transformation from caustic stenosis to esophageal cancer and may serve as future novel biomarkers of malignant progression. This study provides a theoretical basis for future research in this field with this specific pediatric population suffering from caustic exposure. Further investigation is needed to elucidate the mechanisms underlying malignant transformation associated with caustic stenosis. High-risk patients with caustic lesions

Acknowledgments

Research funds were obtained in part from the Brazilian Coordination for the Improvement of Higher Level Education Personnel (CAPES - Brazil) grant #2014/458734-4 to EVPO. GVP was funded through São Paulo Research Foundation (FAPESP - Brazil) scholarship # 2015/03287-4.

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  • 1

    Permanent Address: Department of Pediatric Surgery, Barretos Children's Cancer Hospital from Barretos Cancer Center – Hospital de Cancer de Barretos: Unidade Infantojuvenil; Barretos Medical School – Faculdade de Ciencias da Saúde “Dr Paulo Prata” (FACISB); Av. João Baroni, 3025-Dr. Paulo Prata, Barretos-SP, CEP: 14784-390, Barretos, SP, BRAZIL. Telephone: + 55 (17) 3321 5400.

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