Long non-coding RNA CASC7 is a promising serum biomarker for hepatocellular carcinoma.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968547 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-230X (Electronic) Linking ISSN: 1471230X NLM ISO Abbreviation: BMC Gastroenterol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Carcinoma, Hepatocellular*/diagnosis ; Carcinoma, Hepatocellular*/genetics ; RNA, Long Noncoding*/genetics ; Liver Neoplasms*/diagnosis ; Liver Neoplasms*/genetics; Humans ; Biomarkers ; Area Under Curve

Background: At present, a large number of studies have found that long non-coding RNAs (lncRNAs) can be used as biomarkers for diagnosis and monitoring prognosis of hepatocellular carcinoma (HCC). The expression of lncRNA cancer susceptibility candidate 7 (CASC7) in HCC has rarely been studied. The purpose of this study was to explore the expression of CASC7 and its correlation with clinical features, and to further analyze its diagnostic value in HCC.
Methods: Serum samples were collected from 80 patients with HCC, 80 patients with chronic hepatitis B (CHB), and 80 healthy people. The expression level of serum CASC7 was detected by droplet digital PCR. Appropriate parametric and nonparametric tests were used for data analysis.
Results: The results showed that the expression of CASC7 in serum of patients with HCC was significantly higher than that of patients with CHB (median: 8.8 versus 2.2 copies/µl, p < 0.001) and healthy controls (median: 8.8 versus 3.8 copies/µl, p < 0.001). High expression of serum CASC7 was significantly correlated with tumor number (p = 0.005), intrahepatic metastasis (IM) (p < 0.001), tumor size (p = 0.007) and tumor-node-metastasis (TNM) stage (p = 0.008). The area under the curve (AUC) of CASC7 to distinguish HCC patients from CHB patients and healthy controls was 0.808 (95% CI: 0.742-0.874) at the cut-off value of 7.24 copies/µl with 63.8% sensitivity and 95.2% specificity.
Conclusions: This study suggested that CASC7 was significantly up-regulated in serum of patients with HCC and closely related to tumor number, IM, tumor size and TNM stage, which may serve as a promising diagnostic biomarker.
(© 2023. BioMed Central Ltd., part of Springer Nature.)

Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16(10):589–604. (PMID: 10.1038/s41575-019-0186-y314399376813818)
Kulik L, El-Serag HB. Epidemiology and management of Hepatocellular Carcinoma. Gastroenterology. 2019;156(2):477–. – 91.e1. (PMID: 10.1053/j.gastro.2018.08.06530367835)
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–14. (PMID: 10.1016/S0140-6736(18)30010-229307467)
Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin. 2012;62(6):394–9. (PMID: 10.3322/caac.2116123070690)
Song L, Zhang JG, Zheng L, Feng X, Hou J, Zhang HL, et al. Establishment of rat liver cancer cell lines with different metastatic potential. Sci Rep. 2020;10(1):8329. (PMID: 10.1038/s41598-020-65338-w324335817239898)
Wang N, Wang S, Li MY, Hu BG, Liu LP, Yang SL, et al. Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies. Ther Adv Med Oncol. 2018;10:1–25. (PMID: 10.1177/1758835918816287)
Harding JJ, Khalil DN, Abou-Alfa GK. Biomarkers: what role do they play (if any) for diagnosis, prognosis and Tumor Response Prediction for Hepatocellular Carcinoma? Dig Dis Sci. 2019;64(4):918–27. (PMID: 10.1007/s10620-019-05517-630838478)
Zamcheck N, Pusztaszeri G, CEA. AFP and other potential tumor markers. CA Cancer J Clin. 1975;25(4):204–14. (PMID: 10.3322/canjclin.25.4.20448409)
Fatima R, Akhade VS, Pal D, Rao SM. Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets. Mol Cell Ther. 2015;3:5. (PMID: 10.1186/s40591-015-0042-6260828434469312)
Lanzafame M, Bianco G, Terracciano LM, Ng CKY, Piscuoglio S. The role of long non-coding RNAs in Hepatocarcinogenesis. Int J Mol Sci. 2018;19(3):682. (PMID: 10.3390/ijms19030682294955925877543)
Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66. (PMID: 10.1146/annurev-biochem-051410-09290222663078)
Lennox KA, Behlke MA. Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides. Nucleic Acids Res. 2016;44(2):863–77. (PMID: 10.1093/nar/gkv120626578588)
Zhou X, Lu H, Li F, Han L, Zhang H, Jiang Z, et al. LncRNA cancer susceptibility candidate (CASC7) upregulates phosphatase and tensin homolog by downregulating miR-10a to inhibit neuroblastoma cell proliferation. NeuroReport. 2020;31(5):381–6. (PMID: 10.1097/WNR.000000000000141132101951)
Gong X, Liao X, Huang M. LncRNA CASC7 inhibits the progression of glioma via regulating Wnt/β-catenin signaling pathway. Pathol Res Pract. 2019;215(3):564–70. (PMID: 10.1016/j.prp.2019.01.01830661904)
Zhang Z, Fu C, Xu Q, Wei X. Long non-coding RNA CASC7 inhibits the proliferation and migration of colon cancer cells via inhibiting microRNA-21. Biomed Pharmacother. 2017;95:1644–53. (PMID: 10.1016/j.biopha.2017.09.05228954383)
Chen L, Li X, Lu C, Zhao Y, Zhu J, Yang L. The long non–coding RNA CASC7 inhibits growth and invasion of non–small cell lung cancer cells through phosphatase and tensin homolog upregulation via sequestration of miR–92a. Int J Oncol. 2020;57(2):466–77. (PMID: 10.3892/ijo.2020.5076326269307307594)
Li D, Lu L, Liu M, Sun J. Inhibition of long noncoding RNA cancer susceptibility candidate 7 attenuates hepatocellular carcinoma development by targeting microRNA-30a-5p. Bioengineered. 2022;13(4):11296–308. (PMID: 10.1080/21655979.2022.2068289354849729208517)
Xu YL, Liu Y, Cai RP, He SR, Dai RX, Yang XH, et al. Long non-coding RNA CASC7 is associated with the pathogenesis of heart failure via modulating the expression of miR-30c. J Cell Mol Med. 2020;24(19):11500–11. (PMID: 10.1111/jcmm.15764328604927576250)
Oladapo A, Ito D, Rodriguez AM, Philpott S, Krupnick R, Allen V, et al. Psychometric evaluation of a patient-reported outcomes instrument for congenital thrombotic thrombocytopenic purpura. J Patient Rep Outcomes. 2023;7(1):68. (PMID: 10.1186/s41687-023-00592-w3745020110349015)
Li S, Saviano A, Erstad DJ, Hoshida Y, Fuchs BC, Baumert T, et al. Risk factors, pathogenesis, and strategies for Hepatocellular Carcinoma Prevention: emphasis on secondary Prevention and its translational Challenges. J Clin Med. 2020;9(12):3817. (PMID: 10.3390/jcm9123817332557947760293)
Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62(4):956–67. (PMID: 10.1016/j.jhep.2015.01.00225595883)
Wang H, Lu Z, Zhao X. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer. J Hematol Oncol. 2019;12(1):133. (PMID: 10.1186/s13045-019-0806-6318156336902437)
Chu KK, Cheung TT. Update in management of hepatocellular carcinoma in eastern population. World J Hepatol. 2015;7(11):1562–71. (PMID: 10.4254/wjh.v7.i11.1562260859154462694)
Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg. 2000;232(1):10–24. (PMID: 10.1097/00000658-200007000-00003108621901421103)
Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;132(1):330–42. (PMID: 10.1053/j.gastro.2006.08.02617241883)
Yao Z, Jia C, Tai Y, Liang H, Zhong Z, Xiong Z, et al. Serum exosomal long noncoding RNAs lnc-FAM72D-3 and lnc-EPC1-4 as diagnostic biomarkers for hepatocellular carcinoma. Aging. 2020;12(12):11843–63. (PMID: 10.18632/aging.103355325548647343450)
Yu X, Zhang J, Yang R, Li C. Identification of long noncoding RNA biomarkers for Hepatocellular Carcinoma using single-sample networks. Biomed Res Int. 2020;2020:8579651. (PMID: 10.1155/2020/8579651332998777700720)
Chistiakov DA, Myasoedova VA, Grechko AV, Melnichenko AA, Orekhov AN. New biomarkers for diagnosis and prognosis of localized prostate cancer. Semin Cancer Biol. 2018;52(Pt 1):9–16. (PMID: 10.1016/j.semcancer.2018.01.01229360504)
Vogelstein B, Kinzler KW, Digital PCR. Proc Natl Acad Sci U S A. 1999;96(16):9236–41. (PMID: 10.1073/pnas.96.16.92361043092617763)
Zeng YL, Guo ZY, Su HZ, Zhong FD, Jiang KQ, Yuan GD. Diagnostic and prognostic value of lncRNA cancer susceptibility candidate 9 in hepatocellular carcinoma. World J Gastroenterol. 2019;25(48):6902–15. (PMID: 10.3748/wjg.v25.i48.6902319083946938724)
Fan JC, Zeng F, Le YG, Xin L. LncRNA CASC2 inhibited the viability and induced the apoptosis of hepatocellular carcinoma cells through regulating miR-24-3p. J Cell Biochem. 2018;119(8):6391–7. (PMID: 10.1002/jcb.2647929091305)
Takahashi K, Yan I, Haga H, Patel T. Long noncoding RNA in liver diseases. Hepatology. 2014;60(2):744–53. (PMID: 10.1002/hep.2704324493213)
Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;54(5):1679–89. (PMID: 10.1002/hep.2456321769904)
Xie H, Ma H, Zhou D. Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma. Biomed Res Int. 2013;2013:136106. (PMID: 10.1155/2013/136106237628233674644)
Chalasani NP, Ramasubramanian TS, Bhattacharya A, Olson MC, Edwards VD, Roberts LR, et al. A novel blood-based panel of methylated DNA and protein markers for detection of early-stage Hepatocellular Carcinoma. Clin Gastroenterol Hepatol. 2021;19(12):2597–605e4. (PMID: 10.1016/j.cgh.2020.08.06532889146)
Mohamed AA, Omran D, El-Feky S, Darwish H, Kassas A, Farouk A, et al. Toll-like receptor 7 mRNA is reduced in hepatitis C-based liver cirrhosis and hepatocellular carcinoma, out-performs alpha-fetoprotein levels, and with age and serum aspartate aminotransferase is a new diagnostic index. Br J Biomed Sci. 2021;78(1):18–22. (PMID: 10.1080/09674845.2020.177884232573389)
Kim DJ, Cho EJ, Yu KS, Jang IJ, Yoon JH, Park T, et al. Comprehensive Metabolomic search for biomarkers to Differentiate Early Stage Hepatocellular Carcinoma from Cirrhosis. Cancers (Basel). 2019;11(10):1497. (PMID: 10.3390/cancers1110149731590436)
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264–73e1. (PMID: 10.1053/j.gastro.2011.12.06122537432)
Wen J, Liu Y, Liu J, Liu L, Song C, Han J, et al. Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence both HBV infection and hepatocellular carcinoma development. Mol Carcinog. 2015;54(11):1275–82. (PMID: 10.1002/mc.2220025110835)
Huang JF, Guo YJ, Zhao CX, Yuan SX, Wang Y, Tang GN, et al. Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin. Hepatology. 2013;57(5):1882–92. (PMID: 10.1002/hep.2619523239537)

18-163-15-ZT-001-007-22 Science and Technology Commission of the CMC National Defense Innovation Special Zone; 2018 XLC 2027 Excellent talents fund of Daping Hospital and the major project of Army Medical University

Keywords: Biomarker; CASC7; Diagnosis; Hepatocellular carcinoma; Serum

0 (RNA, Long Noncoding)
0 (Biomarkers)

Date Created: 20230922 Date Completed: 20230925 Latest Revision: 20231122

20231215

PMC10514991

10.1186/s12876-023-02961-7

37735632