Identification of prognostic indicators, diagnostic markers, and possible therapeutic targets among LIM homeobox transcription factors in breast cancer

Cancer Innov. 2022 Sep 26;1(3):252-269. doi: 10.1002/cai2.30. eCollection 2022 Oct.

Abstract

Background: Breast cancer (BRCA) is the most common malignant tumor among women worldwide. Despite advances in treatment, many patients still die from a lack of effective diagnostic and prognostic markers and powerful therapeutic targets. LIM homeobox genes (LHXs) play vital roles in regulating the development of various organisms. However, there are limited reports regarding their roles in the diagnosis, prognosis, and treatment of BRCA.

Methods: UALCAN, Kaplan-Meier plotter, cBioPortal, GeneMANIA, STRING, DAVID 6.8, TRRUST v2, LinkedOmics, and TIMER were utilized to analyze differential expression, prognostic value, genetic alteration, neighbor gene network, transcription factor targets, kinase targets, and immune cell infiltration of LHXs in BRCA patients.

Results: LHX gene expression patterns are clear in BRCA and its different subtypes. Further analyses indicated that this altered expression is possibly affected by genetic and/or epigenetic changes. The prognostic and diagnostic values of certain LHXs are unique to different BRCA subtypes. LHXs are mainly involved in the regulation of differentiation and development, and their neighbor genes are primarily involved in cancer-related pathways. Moreover, most LHXs are closely correlated with immune cell infiltration. Furthermore, LHXs may exert their functions by regulating a series of transcription factor and kinase targets.

Conclusions: LHXs are unique diagnostic and prognostic markers and participate in cancer through different signaling pathways and/or regulatory mechanisms in BRCA. This study provides potential applications of LHXs for the diagnosis, prognosis, and treatment of BRCA and its different subtypes.

Keywords: LIM homeobox genes; breast cancer; diagnostic and prognostic markers; different subtypes; molecular mechanism.