@article{aaeffcfb02b942b1bcd2e4b6d6402a2a,
title = "A 73-gene proliferative transcriptomic signature predicts uterine serous carcinoma patient survival and response to primary therapy",
abstract = "Objectives: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). Methods: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. Results: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10−8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10−12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. Conclusions: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.",
keywords = "Cell proliferation, Gene expression, Prognostic biomarker, Serous, Uterine",
author = "Tran, {Lynn K.H.} and Tran, {Paul M.H.} and Mysona, {David P.} and Purohit, {Sharad B.} and Emily Myers and Lee, {Won Sok} and Boying Dun and Duo Xu and Haitao Liu and Diane Hopkins and John Nechtman and Scelsi, {Chris L.} and Mittal, {Pardeep K.} and Daniel Kleven and Wallbillich, {John J.} and Bunja Rungruang and Sharad Ghamande and She, {Jin Xiong}",
note = "Funding Information: We would like to thank the Georgia Cancer Center Biorepository (Dr. Roni Bollag, Sameera Qureshi), the Georgia Esoteric Medicine Laboratory (Dr. Ravindra Kolhe, Kimya Jones, and Dr. Ashis Mondal), the AU Histology and Electron Microscopy Core (Donna Kumiski, Dr. Brendan Marshall), and the AU Pathology Department (Paulette Clemmons). We would also like to thank all patients who were consented as part of the AU BAT Cancer research project for their generosity, as well as USC patients at AU and affiliate sites (University Hospital, Doctor's Hospital, Trinity Hospital), whose samples were used as part of the retrospective cohort. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. JXS was supported by the Georgia Research Alliance as an eminent scholar. JJW was partially supported by the WRHR program (K12HD085817). Conception and design: LKHT and JXS; provision of patient samples: LKHT, PMHT, DPM, EM, BD, DX, HL, DH, JJW, BR, and SG; provision of clinical data: DPM, WSL, DH, CS, PM, and DK; data acquisition: LKHT, EM, JN, and JXS; data analysis and interpretation: LKHT, PMHT, SBP, JJW, BR, SG, and JXS; manuscript writing: all authors; final approval of manuscript: all authors. Funding Information: JXS was supported by the Georgia Research Alliance as an eminent scholar. JJW was partially supported by the WRHR program ( K12HD085817 ). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = may,
doi = "10.1016/j.ygyno.2020.02.015",
language = "English (US)",
volume = "157",
pages = "340--347",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "2",
}