TY - JOUR
T1 - Expression and clinical role of long non-coding RNA in high-grade serous carcinoma
AU - Filippov-Levy, Natalie
AU - Cohen-Schussheim, Hallel
AU - Tropé, Claes G.
AU - Hetland Falkenthal, Thea E.
AU - Smith, Yoav
AU - Davidson, Ben
AU - Reich, Reuven
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/3
Y1 - 2018/3
N2 - Objective: To profile long non-coding RNA (lncRNA) expression at the various anatomic sites of high-grades serous carcinoma (HGSC) and in effusion-derived exosomes. Methods: LncRNA profiling was performed on 60 HGSC specimens, including 10 ovarian tumors, 10 solid metastases and 10 malignant effusions, as well as exosomes from 30 effusion supernatants. Anatomic site-related expression of ESRG, Link-A, GAS5, MEG3, GATS, PVT1 H19, Linc-RoR, HOTAIR and MALAT1 was validated by quantitative PCR and assessed for clinical relevance in a series of 77 HGSC effusions, 40 ovarian carcinomas, 21 solid metastases and 42 supernatant exosomes. Results: Significantly different (p < 0.05) expression of 241, 406 and 3634 lncRNAs was found in comparative analysis of the ovarian tumors to solid metastases, effusions and exosomes, respectively. Cut-off at two-fold change in lncRNA expression identified 54 lncRNAs present at the 3 anatomic sites and in exosomes. Validation analysis showed significantly different expression of 5 of 10 lncRNAs in the 4 specimen groups (ESRG, Link-A, MEG3, GATS and PVT1, all p < 0.001). Higher ESRG levels in HGSC effusions were associated with longer overall survival in the entire effusion cohort (p = 0.023) and in patients with pre-chemotherapy effusions tapped at diagnosis (p = 0.048). Higher Link-A levels were associated with better overall (p = 0.015) and progression-free (p = 0.023) survival for patients with post-chemotherapy effusions. Link-A was an independent prognostic marker in Cox multivariate analysis in the latter group (p = 0.045). Conclusions: We present the first evidence of differential LncRNA expression as function of anatomic site in HGSC. LncRNA levels in HGSC effusions are candidate prognostic markers.
AB - Objective: To profile long non-coding RNA (lncRNA) expression at the various anatomic sites of high-grades serous carcinoma (HGSC) and in effusion-derived exosomes. Methods: LncRNA profiling was performed on 60 HGSC specimens, including 10 ovarian tumors, 10 solid metastases and 10 malignant effusions, as well as exosomes from 30 effusion supernatants. Anatomic site-related expression of ESRG, Link-A, GAS5, MEG3, GATS, PVT1 H19, Linc-RoR, HOTAIR and MALAT1 was validated by quantitative PCR and assessed for clinical relevance in a series of 77 HGSC effusions, 40 ovarian carcinomas, 21 solid metastases and 42 supernatant exosomes. Results: Significantly different (p < 0.05) expression of 241, 406 and 3634 lncRNAs was found in comparative analysis of the ovarian tumors to solid metastases, effusions and exosomes, respectively. Cut-off at two-fold change in lncRNA expression identified 54 lncRNAs present at the 3 anatomic sites and in exosomes. Validation analysis showed significantly different expression of 5 of 10 lncRNAs in the 4 specimen groups (ESRG, Link-A, MEG3, GATS and PVT1, all p < 0.001). Higher ESRG levels in HGSC effusions were associated with longer overall survival in the entire effusion cohort (p = 0.023) and in patients with pre-chemotherapy effusions tapped at diagnosis (p = 0.048). Higher Link-A levels were associated with better overall (p = 0.015) and progression-free (p = 0.023) survival for patients with post-chemotherapy effusions. Link-A was an independent prognostic marker in Cox multivariate analysis in the latter group (p = 0.045). Conclusions: We present the first evidence of differential LncRNA expression as function of anatomic site in HGSC. LncRNA levels in HGSC effusions are candidate prognostic markers.
KW - Array
KW - Effusion
KW - High-grade serous carcinoma
KW - Long non-coding RNA
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85039970952&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2018.01.004
DO - 10.1016/j.ygyno.2018.01.004
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C2 - 29310950
AN - SCOPUS:85039970952
SN - 0090-8258
VL - 148
SP - 559
EP - 566
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -