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Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions.

ABSTRACT: Triple negative breast cancer (TNBC) is an aggressive tumor with propensity to metastasize and poor treatment options. Improving treatment options would be impactful; thus, finding a tumor-specific cell surface protein with metastasis promoting functions that could be knocked out was the goal of this study. The Otoconin 90 gene (OC90), frequently amplified in tumors on chromosome 8q24.22, was identified as a potential therapeutic candidate. Normally OC90 is expressed in the cochlea with no known function in other normal tissues. In silico analysis of The Cancer Genome Atlas (TCGA) multi-tumor RNAseq cohorts revealed that OC90 is expressed in many tumor types at high prevalence and genomic amplification is associated with the elevated mRNA expression. In vitro assays in TNBC cell lines revealed OC90 expression with control over cell viability, apoptosis and invasion. RNA-seq analysis of OC90-siRNA knockdown and OC90-overexpression in BT20, BT549, HCC38 cell lines identified co-expressed transcripts, HMGA2, POLE2 and TRIB3. Altered expression of HMGA2, POLE2 and TRIB3 was predictive of survival among members of the Metabric breast cancer cohort. Thus, OC90 represents a potential therapeutic target whose knockdown could improve the treatment of TNBC.

SUBMITTER: Pearlman A

PROVIDER: S-EPMC6375562 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions.

Pearlman Alexander A Rahman Mohammed Tanjimur MT Upadhyay Kinnari K Loke Johnny J Ostrer Harry H

PloS one 20190214 2

Triple negative breast cancer (TNBC) is an aggressive tumor with propensity to metastasize and poor treatment options. Improving treatment options would be impactful; thus, finding a tumor-specific cell surface protein with metastasis promoting functions that could be knocked out was the goal of this study. The Otoconin 90 gene (OC90), frequently amplified in tumors on chromosome 8q24.22, was identified as a potential therapeutic candidate. Normally OC90 is expressed in the cochlea with no known ...[more]

PMID: 30763339

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Project description:BackgroundTriple-negative breast cancer is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible.Methodology/principal findingsClinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated by oligonucleotide microarrays. Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A 45-gene prognostic signature giving 98% predictive accuracy in distant recurrence of our triple-negative patients was determined using the receiver operating characteristic analysis and leave-one-out cross validation. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% confidence interval (CI) 1.04-5.06, Cox P=0.04), outperforming five other published breast cancer prognostic signatures. The 45-gene signature identified in this study revealed that TGF-? signaling of immune/inflammatory regulation may play an important role in distant metastatic invasion of triple-negative breast cancer.Conclusions/significanceGene expression data and recurrence information of triple-negative breast cancer were collected and analyzed in this study. A novel set of 45-gene signature was found to be statistically predictive in disease recurrence of triple-negative breast cancer. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of distant recurrence for early-stage triple-negative patients.

Dataset Information

Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions.

Publications

Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions.

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