Abstract
PurposeMRPS23 is recognized as a driver of proliferation in luminal breast cancer. The aims of the present study were to describe MRPS23 copy number change in breast cancer, and to assess associations between MRPS23 copy number change and molecular subtype, proliferation and prognosis, and between MRPS23 gene expression and molecular subtype and prognosis.MethodsUsing fluorescence in situ hybridization (FISH), we examined MRPS23 and centromere 17 copy number in 590 formalin-fixed, paraffin-embedded primary tumours and 144 corresponding lymph node metastases from a cohort of Norwegian breast cancer patients. Furthermore, we analysed MRPS23 gene expression data in 1971 primary breast cancer tumours from the METABRIC dataset. We used Pearson’s χ2 test to assess associations between MRPS23 copy number and molecular subtype and proliferation, and between MRPS23 expression and molecular subtype. We studied prognosis by estimating hazard ratios and cumulative incidence of death from breast cancer according to MRPS23 copy number and MRPS23 expression status.ResultsWe found MRPS23 amplification (mean MRPS23 copy number ≥ 6 and/or MRPS23/chromosome 17 ratio ≥ 2) in 8% of primary tumours. Copy number increase associated with non-basal subtypes and higher tumour cell proliferation (Ki67). Higher MRPS23 expression associated with the Luminal B subtype. We found no significant association between MRPS23 amplification or MRSP23 gene expression, and prognosis.ConclusionAmplification of MRPS23 is associated with higher proliferation and non-basal subtypes in breast cancer. High MRPS23 expression is associated with the Luminal B subtype.
Highlights
Increased proliferation is a hallmark of cancer [1, 2], and identification of genetic drivers of proliferation could be important for prognostication and development of new targeted treatment
Categories defined by Mitochondrial ribosomal protein S23 (MRPS23)/ Categories defined by amplification status chromosome enumeration probe 17 (CEP17) ratio
Contrary to others [3], we found no clear associations between MRPS23 amplification and prognosis in our cohort of Norwegian breast cancer patients
Summary
Increased proliferation is a hallmark of cancer [1, 2], and identification of genetic drivers of proliferation could be important for prognostication and development of new targeted treatment. By high-throughput genomic analyses, Gatza et al identified proliferation driving genes in non-basal breast cancer [3]. Amplification of four of these genes (MRPS23, FGD5, DTX3 and METTL6) was associated with a poor prognosis. High MRPS23 expression has been found in colon [6], cervical [7, 8] and hepatocellular cancer [9, 10], and associated with poor prognosis in non-basal breast cancer [3], hepatocellular [10] and cervical cancer [7, 8]. In a breast cancer mouse model, MRPS23 knock-down reduced proliferation, induced apoptosis and limited angiogenesis and lymph node metastasis [11]
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