TFEB, SIRT1, CARM1, Beclin-1 expression and PITX2 methylation in breast cancer chemoresistance: a retrospective study.
Aged
Aged, 80 and over
Autophagy
/ physiology
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
/ metabolism
Beclin-1
/ metabolism
Breast Neoplasms
/ drug therapy
Case-Control Studies
Chemotherapy, Adjuvant
Drug Resistance, Neoplasm
Female
Homeodomain Proteins
/ metabolism
Humans
Immunohistochemistry
Methylation
Middle Aged
Neoadjuvant Therapy
Neoplasm Recurrence, Local
Prognosis
Protein-Arginine N-Methyltransferases
/ metabolism
Receptor, ErbB-2
/ metabolism
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Sirtuin 1
/ metabolism
Time Factors
Tissue Array Analysis
Transcription Factors
/ metabolism
Homeobox Protein PITX2
Beclin-1
Breast cancer
CARM1
Chemoresistance
PITX2
SIRT1
TFEB
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
18 Oct 2021
18 Oct 2021
Historique:
received:
16
05
2021
accepted:
06
10
2021
entrez:
19
10
2021
pubmed:
20
10
2021
medline:
29
1
2022
Statut:
epublish
Résumé
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. This study aims to evaluate the prognostic impact of TFEB and its pathway in breast cancer chemoresistance. 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. 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. TFEB, SIRT1, and Beclin-1 seem to have a potential prognostic significance in patients with chemo-treated breast cancer, likely because of their role in the regulation of autophagy. In addition, no correlation between TFEB and PITX2 methylation was found, likely because they perform two different roles within the autophagy process.
Sections du résumé
BACKGROUND
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
OBJECTIVE
This study aims to evaluate the prognostic impact of TFEB and its pathway in breast cancer chemoresistance.
METHODS
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
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
CONCLUSIONS
TFEB, SIRT1, and Beclin-1 seem to have a potential prognostic significance in patients with chemo-treated breast cancer, likely because of their role in the regulation of autophagy. In addition, no correlation between TFEB and PITX2 methylation was found, likely because they perform two different roles within the autophagy process.
Identifiants
pubmed: 34663249
doi: 10.1186/s12885-021-08844-y
pii: 10.1186/s12885-021-08844-y
pmc: PMC8524961
doi:
Substances chimiques
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
0
Beclin-1
0
Homeodomain Proteins
0
TFEB protein, human
0
Transcription Factors
0
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
coactivator-associated arginine methyltransferase 1
EC 2.1.1.319
Receptor, ErbB-2
EC 2.7.10.1
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1118Informations de copyright
© 2021. The Author(s).
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