Homologous recombination mRNAs (RAD21, RAD50 and BARD1) have a potentially poor prognostic role in ERBB2-low bladder cancer patients

• Published in: Scientific reports Vol. 13; no. 1; p. 11738
• Main Authors: Albarakati, Nada, Al-Ghamdi, Hanin, Al-Sowayan, Batla, Alshareeda, Alaa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20-07-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 631/67/589; 631/67/589/1336; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Bladder cancer; BRCA1 Protein - genetics; Breast Neoplasms; Cancer; Cell Cycle Proteins - genetics; DNA-Binding Proteins - genetics; ErbB-2 protein; Female; Gene expression; Genomes; Homologous Recombination; Homologous recombination repair; Humanities and Social Sciences; Humans; Malignancy; Metastases; multidisciplinary; Multivariate analysis; Patients; Prognosis; Receptor, ErbB-2 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Survival; Tumor Suppressor Proteins - genetics; Tumors; Ubiquitin-Protein Ligases - genetics; Urinary Bladder Neoplasms - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-38923-y

Human epidermal growth factor receptor 2 (HER2/
ERBB2
) factor is known to be implicated in many malignancies and the potential of it as a prognostic biomarker was reported years ago. Molecular subtypes of HER2/
ERBB2
negative and positive with distinct clinical outcomes have been identified in recent years; however, it is still under investigation for bladder cancer. This study evaluates the biological and prognostic significance of
RAD21
,
RAD50
and
BARD1
(homologous recombination biomarkers) mRNA levels with
ERBB2
low and high expression to explore their impact on bladder cancer patient survival and cancer aggressiveness. The expression of
ERBB2
,
RAD21
,
RAD50
and
BARD1
mRNA levels was assessed in The Cancer Genome Atlas (TCGA) bladder cancer dataset along with four validation cohorts. Outcome analysis was evaluated using disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analysis were used to evaluate the relationship between
RAD21
,
RAD50
,
BARD1
and
ERBB2
expression and clinicopathological variables. A significant increase in mRNA expression levels of
RAD21
,
RAD50
and
BARD1
was noticed in
ERBB2
-low patients compared to
ERBB2
-high patients. This overexpression of the homologous recombination repair transcripts was associated with poor outcome in
ERBB2
-low tumors, not in
ERBB2
-high tumors. Furthermore, the combined expression of high
RAD21
/
RAD50
, high
RAD21
/
BARD1
or high
RAD50
/
BARD1
were significantly associated with worse DFS and a better outcome for those with low co-expression in the
ERBB2
-low cohort. High expression of either
RAD21
/
RAD50
or
RAD21
/
BARD1
in
ERBB2
-low cohort associated with higher chance of metastasis. In addition, gene expression of
BARD1
alone or in combination with
RAD50
acted as an independent prognostic factor for worst survival. The data presented in this study reveal a connection between
RAD21
,
RAD50
,
BARD1
and
ERBB2
and patient survival. Importantly, it provided novel findings and potential prognostic markers, particularly in
ERBB2
-low bladder cancer.