title: Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer.
abstract: Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n =  398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P-values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28-0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25-0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p ≤ 0.007).
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, U.S.A.
authors.forename: Brandon-Luke L
authors.initials: BL
authors.lastname: Seagle
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, U.S.A.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, U.S.A.
authors.forename: Judy Y
authors.initials: JY
authors.lastname: Yeh
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, U.S.A.
authors.forename: Monica
authors.initials: M
authors.lastname: Dandapani
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, U.S.A.
authors.forename: Emily
authors.initials: E
authors.lastname: Schiller
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, U.S.A.
authors.forename: Robert
authors.initials: R
authors.lastname: Samuelson
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, U.S.A.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Prentice Women's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, U.S.A.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Shahabi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D016903:Drug Monitoring / Q000379:methods*; D004358:Drug Therapy / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor