Biomarker potential of the LEF1/TCF family members in breast cancer: Bioinformatic investigation on expression and clinical significance

Lima, Beatriz Miotto; Azevedo, Alexandre Luiz Korte de; Giner, Igor Samesima; Gomig, Talita Helen Bombardelli; Ribeiro, Enilze Maria de Souza Fonseca; Cavalli, Iglenir João

doi:10.1590/1678-4685-GMB-2022-0346

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Genomics and Bioinformatics • Genet. Mol. Biol. 46 (4) • 2023 • https://doi.org/10.1590/1678-4685-GMB-2022-0346 copy

Biomarker potential of the LEF1/TCF family members in breast cancer: Bioinformatic investigation on expression and clinical significance

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The LEF1/TCF transcription factor family is related to the development of diverse tissue types, including the mammary tissue, and dysregulation of its expression and function has been described to favor breast tumorigenesis. However, the clinical and biological relevance of this gene family in breast cancer is still poorly understood. Here, we used bioinformatics approaches aiming to reduce this gap. We investigated its expression patterns in molecular and immune breast cancer subtypes; its correlation with immune cell infiltration, and its prognostic values in predicting outcomes. Also, through regulons construction, we determined the genes whose expression is influenced by these transcription factors, and the pathways in which they are involved. We found that LEF1 and TCF3 are over-expressed in breast tumors regarding non-tumor samples, while TCF4 and TCF7 are down-expressed, with the gene’s methylation status being associated with its expression dysregulation. All four transcription factors presented significance at the diagnostic and prognostic levels. LEF1, TCF4, and TCF7 presented a significant correlation with immune cell infiltration, being associated with the immune subtypes of less favorable outcomes. Altogether, this research contributes to a more accurate understanding of the expression and clinical and biomarker significance of the LEF1/TCF transcription factors in breast cancer.

Keywords:
Breast cancer; LEF1/TCF family; Biomarkers; Bioinformatics

LEF1		TCF3
Subtype comparison	P-value	Subtype comparison	P-value
Basal like = HER2	P-value > 0.05	Basal like = HER2	P-value > 0.05
Basal like < Luminal A	P-value < 0.05	Basal like > Luminal A	P-value < 0.05
Basal like < Luminal B	P-value < 0.05	Basal like > Luminal B	P-value < 0.05
HER2 < Luminal A	P-value < 0.05	HER2 > Luminal A	P-value < 0.05
HER2 < Luminal B	P-value < 0.05	HER2 > Luminal B	P-value < 0.05
Luminal A > Luminal B	P-value < 0.05	Luminal A = Luminal B	P-value > 0.05
TCF4		TCF7
Subtype comparison	P-value	Subtype comparison	P-value
Basal like < HER2	P-value < 0.05	Basal like > HER2	P-value < 0.05
Basal like < Luminal A	P-value < 0.05	Basal like > Luminal A	P-value < 0.05
Basal like < Luminal B	P-value < 0.05	Basal like > Luminal B	P-value < 0.05
HER2 > Luminal A	P-value < 0.05	HER2 = Luminal A	P-value > 0.05
HER2 = Luminal B	P-value > 0.05	HER2 = Luminal B	P-value > 0.05
Luminal A > Luminal B	P-value < 0.05	Luminal A > Luminal B	P-value < 0.05

	LEF1		TCF3		TCF4		TCF7
	Expression	P-value	Expression	P-value	Expression	P-value	Expression	P-value
PR status
PR+ tumors	Higher expression	< 0.001	Lower Expression	<0.0001	Higher expression	<0.0001	Lower expression	<0.0001
PR- tumors	Lower expression	< 0.001	Higher Expression	<0.0001	Lower expression	<0.0001	Higher expression	<0.0001
ER status
ER+ tumors	Higher expression	<0.0001	Lower Expression	<0.0001	Higher expression	<0.0001	Lower expression	0.0163
ER- tumors	Lower expression	<0.0001	Higher Expression	<0.0001	Lower expression	<0.0001	Higher expression	0.0163
HER2 status
HER2+ tumors	Lower expression	<0.0001	Higher Expression	<0.0001	*	0.3131	Higher expression	0.0002
HER2- tumors	Higher expression	<0.0001	Lower Expression	<0.0001	*	0.3131	Lower expression	0.0002
PAM50 & TNBC (IHC) classification
Non-basal-like & Non-TNBC	Higher expression	<0.0001	Lower Expression	<0.0001	Higher expression	<0.0001	Lower expression	<0.0001
Basal-like & TNBC	Lower expression	<0.0001	Higher Expression	<0.0001	Lower expression	<0.0001	Higher expression	<0.0001
Patients age
≤ 51 years	*	0.1025	Higher Expression	<0.0001	Higher expression	<0.0001	Higher expression	0.0005
> 51 years	*	0.1025	Lower Expression	<0.0001	Lower expression	<0.0001	Lower expression	0.0005
TP53 status (IHC)
Wild type	Higher expression	0.0245	Lower Expression	<0.0001	Higher expression	0.0029	Lower expression	0.008
Mutated	Lower expression	0.0245	Higher Expression	<0.0001	Lower expression	0.0029	Higher expression	0.008
Lymph node status
Positive	*	0.4044	*	0.1255	*	0.6552	*	0.0957
Negative	*	0.4044	*	0.1255	*	0.6552	*	0.0957
Nottingham Prognostic Index status (NPI)
	NPI1>NPI2	< 0.01	NPI1=NPI2	0.0716	NPI1 > NPI2	<0.0001	NPI1=NPI2	0.4398
	NPI1>NPI3	< 0.01	NPI1=NPI3		NPI1 > NPI3	<0.0001	NPI1=NPI3
	NPI2=NPI3	0.1	NPI2=NPI3		NPI2 = NPI3	0.1	NPI2=NPI3
Scarff Bloom & Richardson grade status (SBR)
	SBR1=SBR2	> 0.1	SBR1=SBR2	>0.1	SBR1>SBR2	<0.0001	SBR1=SBR2	0.10
	SBR1>SBR3	<0.0001	SBR1>SBR3	<0.0001	SBR1>SBR3	<0.0001	SBR3>SBR1	<0.0001
	SBR2>SBR3	<0.0001	SBR2>SBR3	<0.0001	SBR2>SBR3	<0.0001	SBR3>SBR2	<0.0001

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[1] Send correspondence to
Enilze Maria de Souza Fonseca Ribeiro. Universidade Federal do Paraná, Departamento de Genética, Av. Cel. Francisco H. dos Santos, 100 - Jardim das Américas, 81530-000, Curitiba, PR, Brazil. E-mail: eribeiro@ufpr.br.