TY - JOUR
T1 - Diagnostic Potential of the Serum lncRNAs HOTAIR, BRM and ICR for Hepatocellular Carcinoma
AU - Lou, Zhong Han
AU - Xu, Ke Yang
AU - Qiao, Liang
AU - Su, Xiao Qian
AU - Ou-Yang, Yuan
AU - Miao, Liang Bin
AU - Liu, Fang
AU - Wang, Yi
AU - Fu, Ai
AU - Ren, Xian Hua
AU - Huang, Jing Song
AU - Li, Zhao Yi
AU - Bao, Jian Feng
AU - Huang, Jing Song
N1 - This work has been supported by the Natural Science Foundation of Zhejiang Province (LSY19H030002), the project of Hangzhou Science and Technology Bureau (20181228Y22), the project of Yuhuan Science and Technology Bureau (2018075).
Publisher Copyright:
© 2022 The Author(s). Published by IMR Press.
PY - 2022/9
Y1 - 2022/9
N2 - Background: Long noncoding RNAs (lncRNAs) are closely associated with the initiation, progression, metastasis, and recurrence of hepatocellular carcinoma (HCC). They could therefore serve as markers for the early diagnosis and for the prognosis of HCC patients. Methods: This was an observational prospective cohort study. A total of 101 participants were included, comprising patients with HCC (n = 61), liver cirrhosis (LC) (n = 20), or healthy controls (HC) (n = 20). The baseline characteristics of participants in each group were compared. Serum levels of the lncRNAs HOTAIR, BRM and ICR were determined in each group by reverse transcription and quantitative real-time polymerase chain reaction (qRT-PCR). Correlations between the serum levels of the three lncRNAs and multiple clinical parameters were analysed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic potential for HCC of each lncRNA individually, or in combination with AFP. Multivariate Cox regression analysis was used to evaluate the accuracy of these lncRNAs for predicting the outcome and survival of HCC patients. Results: The serum levels of HOTAIR, BRM and ICR were significantly higher in HCC patients compared to LC patients and healthy subjects. The HOTAIR level was positively correlated to tumour-node metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) stage, extrahepatic metastasis, vascular invasion, portal vein tumour thrombus (PVTT), and tumour size. The BRM level was positively associated with TNM stage, BCLC stage, vascular invasion, PVTT, and tumour size, while the ICR level was positively correlated with PVTT. A combination of the three lncRNAs and AFP showed the highest diagnostic accuracy for HCC, with an AUC of 0.998, sensitivity of 98.4%, and specificity of 100.0%. This combination showed a better diagnostic accuracy than the individual lncRNAs or AFP alone. Serum levels of the HOTAIR and ICR lncRNAs decreased significantly following surgery. Conclusions: Serum levels of the HOTAIR, BRM and ICR lncRNAs are potential prognostic markers for HCC. Upregulation of HOTAIR, BRM and ICR may facilitate early diagnosis and indicate poor prognosis for HCC. These lncRNAs could potentially serve as therapeutic targets for HCC. Combination of the three lncRNAs with AFP may increase the diagnostic accuracy for HCC. Further studies in larger cohorts of patients are needed to validate these findings.
AB - Background: Long noncoding RNAs (lncRNAs) are closely associated with the initiation, progression, metastasis, and recurrence of hepatocellular carcinoma (HCC). They could therefore serve as markers for the early diagnosis and for the prognosis of HCC patients. Methods: This was an observational prospective cohort study. A total of 101 participants were included, comprising patients with HCC (n = 61), liver cirrhosis (LC) (n = 20), or healthy controls (HC) (n = 20). The baseline characteristics of participants in each group were compared. Serum levels of the lncRNAs HOTAIR, BRM and ICR were determined in each group by reverse transcription and quantitative real-time polymerase chain reaction (qRT-PCR). Correlations between the serum levels of the three lncRNAs and multiple clinical parameters were analysed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic potential for HCC of each lncRNA individually, or in combination with AFP. Multivariate Cox regression analysis was used to evaluate the accuracy of these lncRNAs for predicting the outcome and survival of HCC patients. Results: The serum levels of HOTAIR, BRM and ICR were significantly higher in HCC patients compared to LC patients and healthy subjects. The HOTAIR level was positively correlated to tumour-node metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) stage, extrahepatic metastasis, vascular invasion, portal vein tumour thrombus (PVTT), and tumour size. The BRM level was positively associated with TNM stage, BCLC stage, vascular invasion, PVTT, and tumour size, while the ICR level was positively correlated with PVTT. A combination of the three lncRNAs and AFP showed the highest diagnostic accuracy for HCC, with an AUC of 0.998, sensitivity of 98.4%, and specificity of 100.0%. This combination showed a better diagnostic accuracy than the individual lncRNAs or AFP alone. Serum levels of the HOTAIR and ICR lncRNAs decreased significantly following surgery. Conclusions: Serum levels of the HOTAIR, BRM and ICR lncRNAs are potential prognostic markers for HCC. Upregulation of HOTAIR, BRM and ICR may facilitate early diagnosis and indicate poor prognosis for HCC. These lncRNAs could potentially serve as therapeutic targets for HCC. Combination of the three lncRNAs with AFP may increase the diagnostic accuracy for HCC. Further studies in larger cohorts of patients are needed to validate these findings.
KW - diagnosis
KW - Hepatocellular carcinoma
KW - HOX transcript antisense RNA
KW - ICAM-1-related long noncoding RNA
KW - lncRNA for association with Brahma
KW - long noncoding RNAs
KW - serum biomarker
UR - http://www.scopus.com/inward/record.url?scp=85139774711&partnerID=8YFLogxK
U2 - 10.31083/j.fbl2709264
DO - 10.31083/j.fbl2709264
M3 - Journal article
C2 - 36224021
AN - SCOPUS:85139774711
SN - 2768-6701
VL - 27
JO - Frontiers in Bioscience - Landmark
JF - Frontiers in Bioscience - Landmark
IS - 9
M1 - 264
ER -
