Differential MYC and PROM1 mRNA isoform expression in breast invasive carcinoma as biomarkers for subtyping and prognosis.

Background: Cancer stem cells are a subpopulation of tumor cells with the ability to self-renew; evidence suggests that cancer stem cells are responsible for recurrence, metastasis, and resistance to therapy. MYC and CD133 (PROM1 gene) are clinical biomarkers for cancer stem cells, and their dysregulation is involved in the progression of many cancers. Alternative splicing of these genes may contribute to cancer stem cell differentiation.

Methods: Transcriptional and clinical data of PROM1 and MYC mRNA isoforms in breast cancer samples were downloaded from the TCGA Splicing Variants Database site, a web-tool to explore mRNA alternative-splicing based on TCGA samples. Data include RSEM isoform expression, clinical sample types, survival data, and clinical receptor expression. Breast cancer subtypes (luminal A, luminal B, Her2 positive, triple negative) were assigned on the basis of estrogen, progesterone, and HER2 expression.

Results: Expression of MYC isoforms uc003ysh.1 and uc003ysi.3 was significantly greater in triple-negative breast cancer compared with all other breast cancer subtypes (P < .001). Isoform uc003ysi.3 was associated with greater 5-year survival in luminal A breast cancer (hazard ratio, 0.79; 95% confidence interval, 0.65-0.96; P = .02). PROM1 isoforms uc003gop.2, uc003goq.3, uc003gos.2, and uc003gou.2 were expressed greatest in triple-negative breast cancer (P < .001). PROM1 isoform uc003gou.2 was associated with better 5-year survival in luminal A breast cancer (hazard ratio, 0.79; 95% confidence interval, 0.65-0.97; P = .02).

Conclusions: MYC and PROM1 isoforms are differentially expressed in breast cancer subtypes. Certain isoforms confer better survival prognosis. Further work should be done to study alternative splicing in cancer stem cells.