Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Identification of a NACC1-Regulated Gene Signature Impli-Cated in the Features of Triple-Negative Breast Cancer

Xia Liu
* ,
Chrispus Ngule
ORCID logo ,
Hami Hemati
ORCID logo ,
Oluwafunminiyi Obaleye
,
Amos Oyelami
,
Felix Oyelami
,
Xingcong Ren
,
Jianxun Song
ORCID logo ,
Xiaofang Xiong
,
Jin-ming Yang
* ORCID logo
Version 1 : Received: 24 February 2023 / Approved: 27 February 2023 / Online: 27 February 2023 (03:10:34 CET)

A peer-reviewed article of this Preprint also exists.

Ngule, C.M.; Hemati, H.; Ren, X.; Obaleye, O.; Akinyemi, A.O.; Oyelami, F.F.; Xiong, X.; Song, J.; Liu, X.; Yang, J.-M. Identification of a NACC1-Regulated Gene Signature Implicated in the Features of Triple-Negative Breast Cancer. Biomedicines 2023, 11, 1223. Ngule, C.M.; Hemati, H.; Ren, X.; Obaleye, O.; Akinyemi, A.O.; Oyelami, F.F.; Xiong, X.; Song, J.; Liu, X.; Yang, J.-M. Identification of a NACC1-Regulated Gene Signature Implicated in the Features of Triple-Negative Breast Cancer. Biomedicines 2023, 11, 1223.

Abstract

Triple-negative breast cancer (TNBC), characterized by deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotype such as tumor heterogeneity and therapy resistance remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approach, we found 55-up and 9-down regulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration, was positively correlated with status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Also, enhanced infiltration of immunosuppressive cells was positively correlated with the expression of these 5 genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expressions of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.

Keywords

Tumor progression; cancer stem cells; gene signature; NACC1; triple negative breast cancer

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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