环状RNA作为肝细胞癌诊断和预后的生物标志物：一项荟萃分析
安徽医科大学, 卫生学院, 安徽合肥 230032
| 摘 要： | 因为肝细胞癌（HCC）早期诊断困难，缺乏预后评估方法，因此高发病率、高复发率和高死亡率使其成为癌症相关负担和死亡的主要原因。本荟萃分析旨在评估通过综合敏感性、特异性和总生存期（OS）来评估CircRNA在HCC诊断和预后中的效果。PubMed和Web of Science的检索截止到2023年3月，最终检索到诊断31篇，预后37例。结果显示诊断准确率中等，CircRNAs上调的敏感性、特异性和曲线下面积（AUC）分别为0.81（0.73 ~ 0.87）、0.84（0.74 ~ 0.91）和0.90（0.87 ~ 0.92）；下调值分别为0.79（0.70 ~ 0.85）、0.79（0.73 ~ 0.83）、0.85（0.81 ~ 0.88）。对于预后，下调的CircRNAs与更好的OS相关（HR：0.41，0.33 ~ 0.51），而上调的CircRNAs对OS有负面影响（HR：1.77，1.48 ~ 2.12）。综上CircRNA具有较高的诊断准确性，也可作为HCC预后的重要生物标志物。 |
| 关 键 词： | 环状RNA; 肝细胞癌; 生物标志物; 诊断; 预后 |
| DOI： | 10.57237/j.mrf.2023.04.003 |
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收稿日期: 2023-08-29
接受日期: 2023-10-07
在线出版日期: 2023-10-09
Circular RNAs as Diagnostic and Prognostic Biomarkers of Hepatocellular Carcinoma: A Meta-analysis
School of Public Health, Anhui Medical University, Hefei 230032, China
| Abstract: | High morbidity, recurrence and mortality make hepatocellular carcinoma (HCC) a leading cause of cancer-related burden and deaths. However, HCC is still hard to diagnose at an early stage and lack of prognostic evaluation methods. This meta-analysis aims to assess the overall value of circRNA in HCC diagnosis and prognosis. PubMed and Web of Science were searched up to March 2023. The diagnostic and prognostic effect were evaluated by the pooled sensitivity, specificity, and overall survival (OS). In total, 31 for diagnosis and 37 for prognosis were finally included. For diagnosis, the pooled sensitivity, specificity, and the area under curve (AUC) were 0.81 (0.73-0.87), 0.84 (0.74-0.91), and 0.90 (0.87-0.92) for upregulation; and 0.79 (0.70-0.85), 0.79 (0.73-0.83) and 0.85 (0.81-0.88) for downregulation respectively, indicating moderate diagnostic accuracy. For prognosis, downregulated circRNAs were associated with better OS (HR: 0.41, 95% CI: 0.33-0.51), while upregulated circRNAs had a negative influence on OS (HR: 1.77, 1.48-2.12). The circRNA has high diagnostic accuracy and can be used as an important biomarker to prognosticate HCC. |
| Keywords: | Circular RNA; Biomarker; HCC; Diagnosis; Prognosis |
基金
| 1. | 安徽高校自然科学研究项目基金 (KJ2019A0229) |
| 2. | 安徽医学高等专科学校王建华科研创新团队项目基金 (WJH2022004t) |
参考文献
| [1] | Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: New trends [J]. J Hepatol. 2020; 72(2): 250-261. |
| [2] | Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015 [J]. JAMA Oncol. 2017; 3(12): 1683-1691. |
| [3] | Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y, Nakatsura T. Biomarkers for the early diagnosis of hepatocellular carcinoma. World journal of gastroenterology [J]. 2015; 21(37): 10573-105 83. |
| [4] | Khalifa A, Rockey DC. The utility of liver biopsy in 2020. Current opinion in gastroenterology [J]. 2020; 36(3): 184-191. |
| [5] | McGill DB. Liver biopsy: when, how, by whom, and where? Current gastroenterology reports [J]. 2001; 3(1): 19-23. |
| [6] | Hou J, Jiang W, Zhu L, et al. Circular RNAs and exosomes in cancer: a mysterious connection. Clinical & translational oncology: official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [J]. 2018; 20(9): 1109-1116. |
| [7] | Shang W, Adzika GK, Li Y, et al. Molecular mechanisms of circular RNAs, transforming growth factor-β, and long noncoding RNAs in hepatocellular carcinoma. Cancer medicine [J]. 2019; 8(15): 6684-6699. |
| [8] | Beltrán-García J, Osca-Verdegal R, Nacher-Sendra E, Pallardó FV, García-Giménez JL. Circular RNAs in Sepsis: Biogenesis, Function, and Clinical Significance. Cells [J]. 2020; 9(6): 1544. |
| [9] | El Sharkawi FZ, Awad MS, Elagawy W, Al Sawaf HA, Taha H. Circular RNAs 0064286 and 0000475: Potential Diagnostic Biomarkers in Hepatocellular Carcinoma [J]. APJCP. 2021; 22(9): 3039-3044. |
| [10] | Sunagawa Y, Yamada S, Sonohara F, et al. Genome-wide identification and characterization of circular RNA in resected hepatocellular carcinoma and background liver tissue [J]. Scientific reports. 2021; 11(1): 6016. |
| [11] | Nie G, Peng D, Li B, Lu J, Xiong X. Diagnostic Accuracy of Circular RNAs in Different Types of Samples for Detecting Hepatocellular Carcinoma: A Meta-Analysis. Front Genet [J]. 2021; 12: 794105. |
| [12] | Yu G, Yang L, Zhou J, Zhang L, Xia L. Abnormally Expressed Circular RNAs are Promising Biomarkers for Diagnosis of Hepatocellular Carcinoma: a Meta-Analysis [J]. Clinical laboratory. 2019; 65(11): 10.7754/Clin.Lab.2019.190354. |
| [13] | Huang X, Zhang W, Shao Z. Prognostic and diagnostic significance of circRNAs expression in hepatocellular carcinoma patients: A meta-analysis [J]. Cancer medicine. 2019; 8(3): 1148-1156. |
| [14] | Hao Q, Han Y, Xia W, Wang Q, Qian H. Systematic Review and Meta-Analysis of the Utility of Circular RNAs as Biomarkers of Hepatocellular Carcinoma [J]. Canadian journal of gastroenterology & hepatology. 2019; 2019: 1684039. |
| [15] | Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews [J]. J Clin Epidemiol. 2021; 134: 178-189. |
| [16] | Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis [J]. Trials. 2007; 8: 16. |
| [17] | Qu YJ, Yang ZR, Sun F, Zhan SY. [Risk on bias assessment: (6) A Revised Tool for the Quality Assessment on Diagnostic Accuracy Studies (QUADAS-2)] [J]. Zhonghua liuxingbingxue zazhi. 2018; 39(4): 524-531. |
| [18] | Bao Q, Li F, Zheng H, Chen S, Song X. Prognostic role of dysregulated circRNAs in patients with non-small cell lung cancer: a meta-analysis. Journal of thoracic disease [J]. 2020; 12(3): 823-829. |
| [19] | Hamza TH, Arends LR, van Houwelingen HC, Stijnen T. Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds. BMC medical research methodology [J]. 2009; 9: 73. |
| [20] | Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. Journal of clinical epidemiology [J]. 2005; 58(10): 982-990. |
| [21] | Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics in medicine [J]. 2002; 21(11): 1539-1558. |
| [22] | Lin L, Chu H. Quantifying publication bias in meta-analysis. Biometrics [J]. 2018; 74(3): 785-794. |
| [23] | Spineli LM, Pandis N. Publication bias: Graphical and statistical methods. American journal of orthodontics and dentofacial orthopedics: official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics [J]. 2021; 159(2): 248-251. |
| [24] | Zhang Y, Li J, Cui Q, Hu P, Hu S, Qian Y. Circular RNA hsa_circ_0006091 as a novel biomarker for hepatocellular carcinoma. Bioengineered [J]. 2022; 13(2): 1988-2003. |
| [25] | Imanishi S, Nagata S, Fujita T, Fujii H. Circular RNAs hsa_circ_0001438 and hsa_circ_0000417 are downregulated and upregulated, respectively, in hepatocellular carcinoma. Int J Exp Pathol [J]. 2022; 103(6): 245-251. |
| [26] | Lyu L, Yang W, Yao J, et al. The diagnostic value of plasma exosomal hsa_circ_0070396 for hepatocellular carcinoma. Biomarkers in medicine [J]. 2021; 15(5): 359-371. |
| [27] | Zhu C, Su Y, Liu L, Wang S, Liu Y, Wu J. Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells [J]. Frontiers in cell and developmental biology. 2020; 8: 585565. |
| [28] | Liu R, Li Y, Wu A, et al. Identification of Plasma hsa_circ_0005397 and Combined With Serum AFP, AFP-L3 as Potential Biomarkers for Hepatocellular Carcinoma [J]. Frontiers in pharmacology. 2021; 12: 639963. |
| [29] | Guo S, Hu C, Zhai X, Sun D. Circular RNA 0006602 in plasma exosomes: a new potential diagnostic biomarker for hepatocellular carcinoma. American journal of translational research [J]. 2021; 13(6): 6001-6015. |
| [30] | Zhu K, Zhan H, Peng Y, et al. Plasma hsa_circ_0027089 is a diagnostic biomarker for hepatitis B virus-related hepatocellular carcinoma. Carcinogenesis [J]. 2020; 41(3): 296-302. |
| [31] | Sun XH, Wang YT, Li GF, Zhang N, Fan L. Serum-derived three-circRNA signature as a diagnostic biomarker for hepatocellular carcinoma [J]. Cancer cell international. 2020; 20: 226. |
| [32] | Qiao GL, Chen L, Jiang WH, et al. Hsa_circ_0003998 may be used as a new biomarker for the diagnosis and prognosis of hepatocellular carcinoma [J]. OncoTargets and therapy. 2019; 12: 5849-5860. |
| [33] | Zhang X, Xu Y, Qian Z, et al. circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma [J]. Cell death & disease. 2018; 9(11): 1091. |
| [34] | Zhang C, Zhang C, Lin J, Wang H. Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology [J]. 2018; 51(1): 290-300. |
| [35] | Chen D, Zhang C, Lin J, Song X, Wang H. Screening differential circular RNA expression profiles reveal that hsa_circ_0128298 is a biomarker in the diagnosis and prognosis of hepatocellular carcinoma [J]. Cancer management and research. 2018; 10: 1275-1283. |
| [36] | Matboli M, Shafei AE, Ali MA, et al. circRNAs (hsa_circ_00156, hsa_circ _000224, and hsa_circ _000520) are novel potential biomarkers in hepatocellular carcinoma [J]. Journal of cellular biochemistry. 2019; 120(5): 7711-7724. |
| [37] | Shang X, Li G, Liu H, et al. Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development. Medicine. 2016; 95(22): e3811. |
| [38] | Wang Y, Pei L, Yue Z, Jia M, Wang H, Cao LL. The Potential of Serum Exosomal hsa_circ_0028861 as the Novel Diagnostic Biomarker of HBV-Derived Hepatocellular Cancer [J]. Frontiers in genetics. 2021; 12: 703205. |
| [39] | Li Z, Zhou Y, Yang G, et al. Using circular RNA SMARCA5 as a potential novel biomarker for hepatocellular carcinoma. Clinica chimica acta [J]. international journal of clinical chemistry. 2019; 492: 37-44. |
| [40] | Jiang Z, Shen L, Wang S, et al. Hsa_circ_0028502 and hsa_circ_0076251 are potential novel biomarkers for hepatocellular carcinoma [J]. Cancer medicine. 2019; 8(17): 7278-7287. |
| [41] | Zhang X, Zhou H, Jing W, et al. The Circular RNA hsa_circ_0001445 Regulates the Proliferation and Migration of Hepatocellular Carcinoma and May Serve as a Diagnostic Biomarker [J]. Disease markers. 2018; 3073467. |
| [42] | Yao T, Chen Q, Shao Z, Song Z, Fu L, Xiao B. Circular RNA 0068669 as a new biomarker for hepatocellular carcinoma metastasis [J]. Journal of clinical laboratory analysis. 2018; 32(8): e22572: e22239. |
| [43] | Fu L, Wu S, Yao T, et al. Decreased expression of hsa_circ_0003570 in hepatocellular carcinoma and its clinical significance [J]. Journal of clinical laboratory analysis. 2018; 32(2). |
| [44] | Fu L, Yao T, Chen Q, Mo X, Hu Y, Guo J. Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma [J]. Oncotarget. 2017; 8(35): 58405-58416. |
| [45] | Yao Z, Luo J, Hu K, et al. ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways [J]. Molecular oncology. 2017; 11(4): 422-437. |
| [46] | Qin M, Liu G, Huo X, et al. Hsa_circ_0001649: A circular RNA and potential novel biomarker for hepatocellular carcinoma [J]. Cancer biomarkers: section A of Disease markers. 2016; 16(1): 161-169. |
| [47] | Zhang L, Xu T, Li Y, Pang Q, Ding X. Serum hsa_circ_0000615 is a prognostic biomarker of sorafenib resistance in hepatocellular carcinoma. J Clin Lab Anal. 2022; 36(11): e24741. |
| [48] | Zhang P, Sun H, Wen P, Wang Y, Cui Y, Wu J. circRNA circMED27 acts as a prognostic factor and mediator to promote lenvatinib resistance of hepatocellular carcinoma [J]. Mol Ther Nucleic Acids. 2021; 27: 293-303. |
| [49] | Liu L, Du C, Wei X, Liao R. [Correlation of peritumoral circWDR25 expression with the prognosis of patients with hepatocellular carcinoma after curative resection] [J]. Journal of Southern Medical University. 2021; 41(9): 1388-1393. |
| [50] | Li X, Yang J, Yang X, Cao T. Dysregulated circ_0004913, circ_0008160, circ_0000517, and their potential as biomarkers for disease monitoring and prognosis in hepatocellular carcinoma [J]. Journal of clinical laboratory analysis. 2021; 35(6): e23785. |
| [51] | Lin S, Lin Y, Wu Z, et al. circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1 [J]. Frontiers in oncology. 2021; 11: 724415. |
| [52] | Cheng F, Wang L, Zhang J. Circular RNA 0016788 displays as a biomarker for tumor progression and poor prognosis in surgical hepatocellular carcinoma patients [J]. Journal of clinical laboratory analysis. 2020; 34(7): e23300. |
| [53] | Zhao M, Dong G, Meng Q, Lin S, Li X. Circ-HOMER1 enhances the inhibition of miR-1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma cells [J]. Journal of cellular biochemistry. 2020; 121(11): 4440-4449. |
| [54] | Zhou S, Wei J, Wang Y, Liu X. Cisplatin resistance-associated circRNA_101237 serves as a prognostic biomarker in hepatocellular carcinoma [J]. Experimental and therapeutic medicine. 2020; 19(4): 2733-2740. |
| [55] | Zhang PF, Gao C, Huang XY, et al. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma [J]. Molecular cancer. 2020; 19(1): 110. |
| [56] | Sun C, Li G, Liu M. A Novel Circular RNA, circ_0005394, Predicts Unfavorable Prognosis and Contributes to Hepatocellular Carcinoma Progression by Regulating miR-507/E2F3 and miR-515-5p/CXCL6 Signaling Pathways [J]. OncoTargets and therapy. 2020; 13: 6171-6180. |
| [57] | Huang XY, Zhang PF, Wei CY, et al. Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis [J]. Molecular cancer. 2020; 19(1): 92. |
| [58] | Wang X, Wang X, Li W, Zhang Q, Chen J, Chen T. Up-Regulation of hsa_circ_0000517 Predicts Adverse Prognosis of Hepatocellular Carcinoma [J]. Frontiers in oncology. 2019; 9: 1105. |
| [59] | Pan H, Tang L, Jiang H, et al. Enhanced expression of circ_0000267 in hepatocellular carcinoma indicates poor prognosis and facilitates cell progression by sponging miR-646 [J]. Journal of cellular biochemistry. 2019; 120(7): 11350-11357. |
| [60] | Liu L, Qi X, Gui Y, Huo H, Yang X, Yang L. Overexpression of circ_0021093 circular RNA forecasts an unfavorable prognosis and facilitates cell progression by targeting the miR-766-3p/MTA3 pathway in hepatocellular carcinoma [J]. Gene. 2019; 714: 143992. |
| [61] | Yang G, Wang X, Liu B, et al. circ-BIRC6, a circular RNA, promotes hepatocellular carcinoma progression by targeting the miR-3918/Bcl2 axis [J]. Cell cycle (Georgetown, Tex). 2019; 18(9): 976-989. |
| [62] | Sun P, Fan X, Hu X, Fu X, Wei Q, Zang Y. circPCNX and Pecanex Promote Hepatocellular Carcinoma Cell Viability by Inhibiting miR-506 [J]. Cancer management and research. 2019; 11: 10957-10967. |
| [63] | Zhang J, Chang Y, Xu L, Qin L. Elevated expression of circular RNA circ_0008450 predicts dismal prognosis in hepatocellular carcinoma and regulates cell proliferation, apoptosis, and invasion via sponging miR-548p [J]. Journal of cellular biochemistry. 2019; 120(6): 9487-9494. |
| [64] | Li S, Gu H, Huang Y, et al. Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling [J]. Cell cycle (Georgetown, Tex). 2018; 17(19-20): 2349-2359. |
| [65] | Yu J, Xu QG, Wang ZG, et al. Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma [J]. Journal of hepatology. 2018; 68(6): 1214-1227. |
| [66] | Liu H, Xue L, Song C, Liu F, Jiang T, Yang X. Overexpression of circular RNA circ_001569 indicates poor prognosis in hepatocellular carcinoma and promotes cell growth and metastasis by sponging miR-411-5p and miR-432-5p [J]. Biochemical and biophysical research communications. 2018; 503(4): 2659-2665. |
| [67] | Huang XY, Huang ZL, Xu YH, et al. Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-100338/miR-141-3p pathway in hepatitis B-related hepatocellular carcinoma [J]. Scientific reports. 2017; 7(1): 5428. |
| [68] | Jang SY, Kim G, Tak WY, et al. Circular Noncoding RNA hsa_circ_0003570 as a Prognostic Biomarker for Hepatocellular Carcinoma [J]. Genes (Basel). 2022; 13(8): 1484. |
| [69] | Chen F, He L, Qiu L, et al. Circular RNA CircEPB41L2 Functions as Tumor Suppressor in Hepatocellular Carcinoma Through Sponging miR-590-5p [J]. Cancer management and research. 2021; 13: 2969-2981. |
| [70] | Kim G, Han JR, Park SY, et al. Circular noncoding RNA hsa_circ_0005986 as a prognostic biomarker for hepatocellular carcinoma [J]. Scientific reports. 2021; 11(1): 14930. |
| [71] | Zhang PF, Wei CY, Huang XY, et al. Circular RNA circTRIM33-12 acts as the sponge of MicroRNA-191 to suppress hepatocellular carcinoma progression [J]. Molecular cancer. 2019; 18(1): 105. |
| [72] | Zhang X, Qiu S, Luo P, et al. Down-regulation of hsa_circ_0001649 in hepatocellular carcinoma predicts a poor prognosis [J]. Cancer biomarkers: section A of Disease markers. 2018; 22(1): 135-142. |
| [73] | Zhong L, Wang Y, Cheng Y, et al. Circular RNA circC3P1 suppresses hepatocellular carcinoma growth and metastasis through miR-4641/PCK1 pathway [J]. Biochemical and biophysical research communications. 2018; 499(4): 1044-1049. |
| [74] | Guo W, Zhang J, Zhang D, et al. Polymorphisms and expression pattern of circular RNA circ-ITCH contributes to the carcinogenesis of hepatocellular carcinoma [J]. Oncotarget. 2017; 8(29): 48169-48177. |
| [75] | Han D, Li J, Wang H, et al. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression [J]. Hepatology (Baltimore, Md). Oct 2017; 66(4): 1151-1164. |
| [76] | Ma Y, Niu X, Yan S, Liu Y, Dong R, Li Y. Circular RNA profiling facilitates the diagnosis and prognostic monitoring of breast cancer: A pair-wise meta-analysis [J]. J Clin Lab Anal. 2021; 35(1): e23575. |
| [77] | Lin Y, Luo X, Cui Z, Chen Y. Diagnostic Potential for Circular RNAs in Gastric Carcinoma: a Meta-Analysis [J]. Clin Lab. 2019; 65(3): 10.7754/Clin.Lab.2018.180810. |
| [78] | Li RD, Guan M, Zhou Z, Dong SX, Liu Q. The Role of circRNAs in the Diagnosis of Colorectal Cancer: A Meta-Analysis [J]. Front Med (Lausanne). 2021; 8: 766208. |
| [79] | Yang Q, Chen L, Yang L, Huang Y. Diagnostic and prognostic values of circular RNAs for lung cancer: a meta-analysis [J]. Postgrad Med J. 2021; 97(1147): 286-293. |
| [80] | Zhang Y, Yang X, Zhuang Z, et al. The diagnostic value of exosomal circular RNAs in cancer patients: A systematic review and meta-analysis [J]. Cancer Med. 2023; 12(2): 1709-1720. |
| [81] | Walter SD. The partial area under the summary ROC curve. Statistics in medicine [J]. 2005; 24(13): 2025-2040. |
| [82] | Walter SD. Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Statistics in medicine [J]. 2002; 21(9): 1237-1256. |
| [83] | Chen Z, Zhang L, Han G, et al. A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy [J]. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology. 2018; 45(3): 962-972. |
| [84] | Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM. The diagnostic odds ratio: a single indicator of test performance [J]. Journal of clinical epidemiology. 2003; 56(11): 1129-1135. |
| [85] | Ding HX, Lv Z, Yuan Y, Xu Q. The expression of circRNAs as a promising biomarker in the diagnosis and prognosis of human cancers: a systematic review and meta-analysis [J]. Oncotarget. 2018; 9(14): 11824-11836. |
| [86] | Jiang YL, Shang MM, Dong SZ, Chang YC. Abnormally expressed circular RNAs as novel non-invasive biomarkers for hepatocellular carcinoma: A meta-analysis [J]. World J Gastrointest Oncol. 2019; 11(10): 909-924. |
| [87] | Zhang H, Ding R, Chen D. Value of miR-21 levels as potential biomarkers in the early diagnosis of hepatocellular carcinoma: a meta-analysis [J]. Biomarkers. 2021; 26(7): 586-597. |
