| Abstrakt: |
Tumor recurrence, following initial response to adjuvant chemotherapy, is a major problem in women with high-grade serous ovarian cancer (HGSOC). Microarray analysis of primary tumors has identified genes that may be useful in risk stratification/overall survival, but are of limited value in predicting the >70% rate for tumor recurrence. In this study, we performed RNA-Seq analysis of primary and recurrent HGSOC to first identify unique differentially expressed genes. From this dataset, we selected 21 archetypical coding genes and one noncoding RNA, based on statistically significant differences in their expression profile between tumors, for validation by qPCR in a larger cohort of 110 ovarian tumors (71 primary and 39 recurrent) and for testing association of specific genes with time-to-recurrence (TTR). Kaplan–Meier tests revealed that high expression of collagen type II, alpha 1 (COL2A1) was associated with delayed TTR (HR50.47, 95% CI: 0.27–0.82, p50.008), whereas low expression of the pseudogene, solute carrier family 6 member 10 (SLC6A10P), was associated with longer TTR (HR50.53, 95% CI: 0.30–0.93, p50.027). Notably, TTR was significantly delayed for tumors that simultaneously highly expressed COL2A1 and lowly expressed SLC6A10P (HR50.21, 95% CI: 0.082–0.54, p50.0011), an estimated median of 95 months as compared to an estimated median of 16 months for subjects expressing other levels of COL2A1 and SLC6A10P. Thus, evaluating expression levels of COL2A1 and SLC6A10P at primary surgery could be beneficial for clinically managing recurrence of HGSOC. What’s new? While tumor debulking surgery followed by adjuvant chemotherapy leads to a favorable response in most patients with high grade serous ovarian cancer (HGSOC), recurrence is frequent. Due to limitations in microarray technology, here the authors used RNA-Seq analysis of primary and recurrent HGSOC to identify unique differentially expressed RNAs, including non-coding transcripts, that may predict recurrence. The results reveal that simultaneous high expression of COL2A1 and low expression of pseudogene SLC6A10P were associated with significantly delayed tumor recurrence. Thus, determining expression levels of COL2A1 and SLC6A10P at primary surgery could be beneficial for predicting and clinically managing recurrence of HGSOC. [ABSTRACT FROM AUTHOR] |
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