| Title: |
TFEB, SIRT1, CARM1, Beclin-1 expression and PITX2 methylation in breast cancer chemoresistance: a retrospective study |
| Authors: |
Bertozzi S.; Londero A. P.; Viola L.; Orsaria M.; Bulfoni M.; Marzinotto S.; Corradetti B.; Baccarani U.; Cesselli D.; Cedolini C.; Mariuzzi L. |
| Contributors: |
Bertozzi, S.; Londero, A. P.; Viola, L.; Orsaria, M.; Bulfoni, M.; Marzinotto, S.; Corradetti, B.; Baccarani, U.; Cesselli, D.; Cedolini, C.; Mariuzzi, L. |
| Publication Year: |
2021 |
| Collection: |
Università degli Studi di Udine: CINECA IRIS |
| Subject Terms: |
Beclin-1; Breast cancer; CARM1; Chemoresistance; PITX2; SIRT1; TFEB |
| Description: |
Background: Breast cancer chemoresistance is attributed to a wide variety of mechanisms, including autophagy. Transcription factor EB (TFEB) has been recently identified and characterized as one major regulator of autophagy and lysosomal genesis. Objective: This study aims to evaluate the prognostic impact of TFEB and its pathway in breast cancer chemoresistance. Methods: This retrospective study analyzes the expression of TFEB, CARM1, SIRT1, and Beclin-1 and the methylation of PITX2 in breast carcinoma. A group of breast cancer patients treated with chemotherapy, who relapsed within 12 months from treatment initiation, were compared to a sub-cohort of chemo-treated patients who did not recur within 12 months of follow-up. The expression of TFEB, CARM1, SIRT1, and Belcin-1 was analyzed using immunohistochemistry or RT-PCR on formalin-fixed paraffin-embedded samples. PITX2 methylation was tested with the diagnostic CE-marked kit Therascreen PITX2 RGQ PCR. In the final model, 136 cases of chemo-treated breast cancer were included. Results: A higher TFEB and Beclin-1 expression correlate with shorter survival in patients with chemo-treated invasive breast cancer (respectively HR 3.46, CI.95 1.27–9.47, p < 0.05 and 7.11, CI.95 2.54–19.9). TFEB, CARM1, and SIRT1 are positively correlated with Beclin-1. The protein expression of SIRT1 is significantly associated with TFEB and CARM1 so that a very low SIRT1 expression (lower than the first quartile of the H-score distribution) correlates with a low expression of TFEB and CARM1 and with longer survival. SIRT1 seems to have a lower H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. Beclin-1 and TFEB seem to have a higher H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. PITX2 methylation analysis was feasible only in 65% of the selected samples, but no significant differences between cases and controls were found, and there was also no correlation with the expression of the TFEB pathway. Conclusions: TFEB, SIRT1, ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/WOS:000708490200005; volume:21; issue:1; firstpage:1118; journal:BMC CANCER; https://hdl.handle.net/11390/1214014 |
| DOI: |
10.1186/s12885-021-08844-y |
| Availability: |
https://hdl.handle.net/11390/1214014; https://doi.org/10.1186/s12885-021-08844-y |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.52C43B9C |
| Database: |
BASE |