Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients.
Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China.
Rong
R
Liu
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China.
Ying
Y
Zeng
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China.
Cheng-Fang
CF
Zhou
The Affiliated Cancer Hospital of XiangYa School of Medicine, Central South University, Changsha, Hunan, 410014, P. R. China.
Ying
Y
Wang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China.
Xi
X
Li
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China.
Zhao-Qian
ZQ
Liu
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China.
Xiao-Ping
XP
Chen
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China. yjsd2003@163.com.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China. yjsd2003@163.com.
Wei
W
Zhang
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China. HHZhou2003@163.com.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P. R. China. HHZhou2003@163.com.
Hong-Hao
HH
Zhou
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017671:Platinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D017671:Platinum Compounds; D062085:RNA, Long Noncoding; D002945:Cisplatin