Autophagy and nuclear morphometry are associated with histopathologic features in esophageal squamous cell carcinoma

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 102; no. 1; pp. 39 - 52
• Main Authors: Iserhard, Ricardo, Pilar, Emily Ferreira Salles, de Oliveira, Francine Hehn, Callegari-Jacques, Sidia Maria, Ferst, Paula, Visioli, Fernanda, Lopes, Antonio Barros, da Costa Lopez, Patrícia Luciana, Filippi-Chiela, Eduardo Cremonese
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2024; Springer Nature B.V
• Subjects: Autophagy; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Carcinoma, Squamous Cell - pathology; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - metabolism; Esophageal Squamous Cell Carcinoma - pathology; Human Genetics; Humans; Internal Medicine; Lymphocytes; Molecular Medicine; Morphometry; Original Article; Parenchyma; Prognosis; Sequestosome-1 Protein - genetics; Sequestosome-1 Protein - metabolism; Squamous cell carcinoma; Tumor-infiltrating lymphocytes; Tumors; Histopathology; Prognosis; Autophagy; Nuclear morphometry; Esophageal squamous cell carcinoma (ESCC)
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-023-02387-4

Less than 15% of patients with esophageal squamous cell carcinoma (ESCC) survive 5 years after diagnosis. A better understanding of the biology of these tumors and the development of clinical biomarkers is needed. Autophagy is a physiological mechanism involved in the turnover of cellular components that plays a key role in cancer. This study evaluated the differential levels of three key regulators of autophagy (SQSTM1, MAP1LC3B, and BECN1) in patients with ESCC, associating autophagy with histopathologic features, including the grade of differentiation, mitotic rate, inflammation score, and the intensity of tumor-infiltrating lymphocytes. Nuclear morphometry of the tumor parenchyma was also assessed, associating it with autophagy and histopathology. All three markers significantly increased in patients with ESCC compared to the control group. Based on the mean expression of each protein in the control group, 57% of patients with ESCC had high levels of all three markers compared to control patients (14%). The most frequent profiles found in ESCC were BECN high /MAP1LC3 high and BECN high /SQSTM1 high . According to the TCGA database, we found that the main autophagy genes were upregulated in ESCC. Moreover, high levels of autophagy markers were associated with a poor prognosis. Considering nuclear morphometry, ESCC samples showed a significant reduction in nuclear area, which was strongly negatively correlated with autophagy. Finally, the percentage of normal nuclei was associated with tumor differentiation, while poorly differentiated tumors showed lower SQSTM1 levels. ESCC progression may involve increased autophagy and changes in nuclear structure, associated with clinically relevant histopathological features. Key messages Autophagy markers are co-increased in primary ESCC. Autophagy negatively correlates with nuclear morphometry in ESCC parenchyma. Autophagy and nuclear morphometry are associated with histopathological features. Autophagy is increased in ESCC-TCGA database and associated with poor prognosis.