title: Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer.
abstract: 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 (HR = 0.47, 95% CI: 0.27-0.82, p = 0.008), whereas low expression of the pseudogene, solute carrier family 6 member 10 (SLC6A10P), was associated with longer TTR (HR = 0.53, 95% CI: 0.30-0.93, p = 0.027). Notably, TTR was significantly delayed for tumors that simultaneously highly expressed COL2A1 and lowly expressed SLC6A10P (HR = 0.21, 95% CI: 0.082-0.54, p = 0.0011), 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.
authors: Department of Cancer Pharmacology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC.
authors: Mahrukh K
authors: MK
authors: Ganapathi
authors: Genomics and Bioinformatics Group, Expression Analysis-Quintiles, Durham, NC.
authors: Wendell D
authors: WD
authors: Jones
authors: Department of Gynecology, Charité Medical University of Berlin, Berlin, Germany.
authors: Jalid
authors: J
authors: Sehouli
authors: Women's Health and Obstetrics/Gynecology Institute, Cleveland Clinic, Cleveland, OH.
authors: Chad M
authors: CM
authors: Michener
authors: Department of Gynecology, Charité Medical University of Berlin, Berlin, Germany.
authors: Ioana E
authors: IE
authors: Braicu
authors: Department of Cancer Pharmacology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC.
authors: Eric J
authors: EJ
authors: Norris
authors: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH.
authors: Charles V
authors: CV
authors: Biscotti
authors: Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors: Susan A J
authors: SA
authors: Vaziri
authors: Department of Cancer Pharmacology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC.
authors: Ram N
authors: RN
authors: Ganapathi
mesh_terms: D000328:Adult; D000368:Aged; D024043:Collagen Type II / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011544:Pseudogenes; D017423:Sequence Analysis, RNA
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D026901:Membrane Transport Proteins; C080679:creatine transporter
keywords: COL2A1; RNA-Seq; SLC6A10P; high-grade serous ovarian cancer; pseudogene; tumor recurrence