Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Systematic Review Article

Apolipoprotein A-1 as a Potential Biomarker for Solid Tumors: A Systematic Review and Meta-Analysis

Author(s): Amir Hossein Aalami*, Farnoosh Aalami and Amirhossein Sahebkar*

Volume 30, Issue 29, 2023

Published on: 22 March, 2023

Page: [3356 - 3367] Pages: 12

DOI: 10.2174/0929867330666230210112700

Price: $65


Background: The diagnostic value of apolipoprotein A-I (ApoA-I) as a marker of different malignancies has been reported in several investigations; however, the results have been contradictory. The current meta-analysis examined the association between ApoA-I levels and human malignancies.

Methods: We reviewed the databases and retrieved papers for analysis until November 1st, 2021. Random-effects meta-analysis was performed to construct the pooled diagnostic parameters. To find the causes of heterogeneity, we utilized Spearman threshold effect analysis and subgroup analysis. The I2 and Chi-square tests were used to examine the heterogeneity. Moreover, subgroup analyses were performed based on sample type (serum/urine) and geographical region of study. Finally, publication bias was explored using Begg's and Egger’s tests.

Results: A total of 11 articles involving 4,121 participants (2,430 cases and 1,691 controls) were included. The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.764 (95% CI: 0.746 - 0.781), 0.795 (95% CI: 0.775 - 0.814), 5.105 (95% CI: 3.313 - 7.865), 0.251 (95% CI: 0.174 - 0.364), 24.61 (95% CI: 12.22 - 49.54), and 0.93, respectively. In subgroup analyses, better diagnostic values were found for urine samples and East Asian Countries (China, Korea, and Taiwan).

Conclusion: Urinary ApoA-I levels may serve as a favorable diagnostic marker for cancer.

Keywords: Apolipoprotein A-I (ApoA-1), cancer, serum, urine, diagnosis, biomarker.

Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[] [PMID: 30207593]
Hasan, M.; Ahommed, M.; Daizy, M.; Bacchu, M.; Ali, M.; Al-Mamun, M. Recent development in electrochemical biosensors for cancer biomarkers detection. Biosens. Bioelectron., 2021, X, 100075.
Bonatelli, M.; Fornari, I.F.; Bernécule, P.N.; Pinheiro, L.E.; Costa, R.F.A.; Longatto-Filho, A.; Junior, J.N.A.; Silva, E.C.A.; Cárcano, F.M.; Pinheiro, C. Expression of glycolysis-related proteins in cancer of unknown primary origin. Front. Oncol., 2021, 11, 682665.
[] [PMID: 34249728]
Jiang, R.; Yang, Z.H.; Luo, D.H.; Guo, L.; Sun, R.; Chen, Q.Y.; Huang, P.Y.; Qiu, F.; Zou, X.; Cao, K.J.; Mai, H.Q.; Guo, X.; Qian, C.N.; Hong, M.H.; Chen, M.Y. Elevated apolipoprotein A-I levels are associated with favorable prognosis in metastatic nasopharyngeal carcinoma. Med. Oncol., 2014, 31(8), 80.
[] [PMID: 25023050]
Gao, F.; Vasquez, S.X.; Su, F.; Roberts, S.; Shah, N.; Grijalva, V.; Imaizumi, S.; Chattopadhyay, A.; Ganapathy, E.; Meriwether, D.; Johnston, B.; Anantharamaiah, G.M.; Navab, M.; Fogelman, A.M.; Reddy, S.T.; Farias-Eisner, R. L-5F, an apolipoprotein A-I mimetic, inhibits tumor angiogenesis by suppressing VEGF/basic FGF signaling pathways. Integr. Biol., 2011, 3(4), 479-489.
[] [PMID: 21283904]
Magray, J.A.; Pandith, A.A.; Qasim, I.; Khateeb, M.; Hamid, A.; Koul, A.; Shah, Z.A.; Baba, S.M.; Mansoor, S.; Charifi, W.; Ahmad, A.; Wani, M.S. Significant implications of APOA1 gene sequence variations and its protein expression in bladder cancer. Biomedicines, 2021, 9(8), 938.
[] [PMID: 34440141]
Kim, S.E.; Kim, Y.J.; Song, S.; Lee, K.N.; Seong, W.K. A simple electrochemical immunosensor platform for detection of Apolipoprotein A1 (Apo-A1) as a bladder cancer biomarker in urine. Sens. Actuators B Chem., 2019, 278, 103-109.
Yelamanchili, D.; Liu, J.; Gotto, A.M., Jr; Hurley, A.E.; Lagor, W.R.; Gillard, B.K.; Davidson, W.S.; Pownall, H.J.; Rosales, C. Highly conserved amino acid residues in apolipoprotein A1 discordantly induce high density lipoprotein assembly in vitro and in vivo. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2020, 1865(12), 158794.
[] [PMID: 32810603]
McInnes, M.D.F.; Moher, D.; Thombs, B.D.; McGrath, T.A.; Bossuyt, P.M.; Clifford, T.; Cohen, J.F.; Deeks, J.J.; Gatsonis, C.; Hooft, L.; Hunt, H.A.; Hyde, C.J.; Korevaar, D.A.; Leeflang, M.M.G.; Macaskill, P.; Reitsma, J.B.; Rodin, R.; Rutjes, A.W.S.; Salameh, J.P.; Stevens, A.; Takwoingi, Y.; Tonelli, M.; Weeks, L.; Whiting, P.; Willis, B.H. Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: the PRISMA-DTA statement. JAMA, 2018, 319(4), 388-396.
[] [PMID: 29362800]
Okuda, M.; Kamiya, S.; Booka, M.; Kikuchi, S.; Osaki, T.; Hiwatani, T.; Maekawa, K.; Fukuda, Y. Diagnostic accuracy of urine-based kits for detection of Helicobacter pylori antibody in children. Pediatr. Int., 2013, 55(3), 337-341.
[] [PMID: 23360308]
Aalami, A.H.; Abdeahad, H.; Mesgari, M.; Sahebkar, A. MiRNA-223 in gastrointestinal cancers: A systematic review and diagnostic meta-analysis. Eur. J. Clin. Invest., 2021, 51(2), e13448.
[] [PMID: 33244751]
Gourin, C.G.; Zhi, W.; Adam, B.L. Proteomic identification of serum biomarkers for head and neck cancer surveillance. Laryngoscope, 2009, 119(7), 1291-1302.
[] [PMID: 19444892]
Mao, M.; Wang, X.; Sheng, H.; Liu, Y.; Zhang, L.; Dai, S.; Chi, P. A novel score based on serum apolipoprotein A-1 and C-reactive protein is a prognostic biomarker in hepatocellular carcinoma patients. BMC Cancer, 2018, 18(1), 1178.
[] [PMID: 30486825]
Chang, Y-K.; Lai, Y-H.; Chu, Y.; Lee, M-C.; Huang, C-Y.; Wu, S. Haptoglobin is a serological biomarker for adenocarcinoma lung cancer by using the ProteomeLab PF2D combined with mass spectrometry. Am. J. Cancer Res., 2016, 6(8), 1828-1836.
[PMID: 27648369]
Shi, H.; Huang, H.; Pu, J.; Shi, D.; Ning, Y.; Dong, Y.; Han, Y.; Zarogoulidis, P.; Bai, C. Decreased pretherapy serum apolipoprotein A-I is associated with extent of metastasis and poor prognosis of non-small-cell lung cancer. OncoTargets Ther., 2018, 11, 6995-7003.
[] [PMID: 30410356]
Ehmann, M.; Felix, K.; Hartmann, D.; Schnölzer, M.; Nees, M.; Vorderwülbecke, S.; Bogumil, R.; Büchler, M.W.; Friess, H. Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling. Pancreas, 2007, 34(2), 205-214.
[] [PMID: 17312459]
Farias-Eisner, G.; Su, F.; Robbins, T.; Kotlerman, J.; Reddy, S.; Farias-Eisner, R. Validation of serum biomarkers for detection of early-and late-stage endometrial cancer. Am. J. Obstet. Gynecol., 2010, 202(1), 73, e1-e5.
Ahn, H.S.; Shin, Y.S.; Park, P.J.; Kang, K.N.; Kim, Y.; Lee, H-J.; Yang, H-K.; Kim, C.W. Serum biomarker panels for the diagnosis of gastric adenocarcinoma. Br. J. Cancer, 2012, 106(4), 733-739.
[] [PMID: 22240791]
Salem, H.; Ellakwa, D.E.S.; Fouad, H.; Hamid, M.A. APOA1 AND APOA2 proteins as prognostic markers for early detection of urinary bladder cancer. Gene Rep., 2019, 16, 100463.
Li, H.; Li, C.; Wu, H.; Zhang, T.; Wang, J.; Wang, S.; Chang, J. Identification of Apo-A1 as a biomarker for early diagnosis of bladder transitional cell carcinoma. Proteome Sci., 2011, 9(1), 21.
[] [PMID: 21496341]
Li, C.; Li, H.; Zhang, T.; Li, J.; Liu, L.; Chang, J. Discovery of Apo-A1 as a potential bladder cancer biomarker by urine proteomics and analysis. Biochem. Biophys. Res. Commun., 2014, 446(4), 1047-1052.
[] [PMID: 24661883]
Chen, Y.T.; Chen, C.L.; Chen, H.W.; Chung, T.; Wu, C.C.; Chen, C.D.; Hsu, C.W.; Chen, M.C.; Tsui, K.H.; Chang, P.L.; Chang, Y.S.; Yu, J.S. Discovery of novel bladder cancer biomarkers by comparative urine proteomics using iTRAQ technology. J. Proteome Res., 2010, 9(11), 5803-5815.
[] [PMID: 20806971]
Zhu, Y.M.; Verma, S.; Fung, M.; McQueen, M.J.; Anderson, T.J.; Lonn, E.M. Association of apolipoproteins B and A-1 with markers of vascular health or cardiovascular events. Can. J. Cardiol., 2017, 33(10), 1305-1311.
[] [PMID: 28941609]
Yao, X.; Gordon, E.M.; Figueroa, D.M.; Barochia, A.V.; Levine, S.J. Emerging roles of apolipoprotein E and apolipoprotein AI in the pathogenesis and treatment of lung disease. Am. J. Respir. Cell Mol. Biol., 2016, 55(2), 159-169.
[] [PMID: 27073971]
Gorabi, A.M.; Kiaie, N.; Khosrojerdi, A.; Jamialahmadi, T.; Al-Rasadi, K.; Johnston, T.P. Implications for the role of lipopolysaccharide in the development of atherosclerosis. Trends Cardiovasc. Med., 2021, 32(8), 525-533.
[PMID: 34492295]
Zhao, T.J.; Zhu, N.; Shi, Y.N.; Wang, Y.X.; Zhang, C.J.; Deng, C.F.; Liao, D.F.; Qin, L. Targeting HDL in tumor microenvironment: New hope for cancer therapy. J. Cell. Physiol., 2021, 236(11), 7853-7873.
[] [PMID: 34018609]
Gkouskou, K.K.; Ioannou, M.; Pavlopoulos, G.A.; Georgila, K.; Siganou, A.; Nikolaidis, G.; Kanellis, D.C.; Moore, S.; Papadakis, K.A.; Kardassis, D.; Iliopoulos, I.; McDyer, F.A.; Drakos, E.; Eliopoulos, A.G. Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis. Oncogene, 2016, 35(19), 2496-2505.
[] [PMID: 26279300]
Kim, K.; Kim, M.J.; Kim, K.H.; Ahn, S.A.; Kim, J.H.; Cho, J.Y.; Yeo, S.G. C1QBP is upregulated in colon cancer and binds to apolipoprotein A-I. Exp. Ther. Med., 2017, 13(5), 2493-2500.
[] [PMID: 28565870]
Georgila, K.; Gounis, M.; Havaki, S.; Gorgoulis, V.G.; Eliopoulos, A.G. mTORC1-dependent protein synthesis and autophagy uncouple in the regulation of Apolipoprotein A-I expression. Metabolism, 2020, 105, 154186.
[] [PMID: 32084429]
O’Sullivan, P.; Sharples, K.; Dalphin, M.; Davidson, P.; Gilling, P.; Cambridge, L.; Harvey, J.; Toro, T.; Giles, N.; Luxmanan, C.; Alves, C.F.; Yoon, H.S.; Hinder, V.; Masters, J.; Kennedy-Smith, A.; Beaven, T.; Guilford, P.J. A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria. J. Urol., 2012, 188(3), 741-747.
[] [PMID: 22818138]
Batista, R.; Vinagre, N.; Meireles, S.; Vinagre, J.; Prazeres, H.; Leão, R.; Máximo, V.; Soares, P. Biomarkers for bladder cancer diagnosis and surveillance: A comprehensive review. Diagnostics (Basel), 2020, 10(1), 39.
[] [PMID: 31941070]
Liu, X.; Zheng, W.; Wang, W.; Shen, H.; Liu, L.; Lou, W.; Wang, X.; Yang, P. A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline. Br. J. Cancer, 2017, 117(12), 1846-1854.
[] [PMID: 29123261]
Kozak, K.R.; Su, F.; Whitelegge, J.P.; Faull, K.; Reddy, S.; Farias-Eisner, R. Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics, 2005, 5(17), 4589-4596.
[] [PMID: 16237736]
Ai, J.; Tan, Y.; Ying, W.; Hong, Y.; Liu, S.; Wu, M.; Qian, X.; Wang, H. Proteome analysis of hepatocellular carcinoma by laser capture microdissection. Proteomics, 2006, 6(2), 538-546.
[] [PMID: 16342242]
Zhang, Y.; Yang, X. Prognostic significance of pretreatment apolipoprotein AI as a noninvasive biomarker in cancer survivors: A meta-analysis. Disease Markers, 2018, 2018, 1034037.
Wu, J.; Zhang, C.; Zhang, G.; Wang, Y.; Zhang, Z.; Su, W.; Lyu, J. Association between pretreatment serum apolipoprotein A1 and prognosis of solid tumors in Chinese population: A systematic review and meta-analysis. Cell. Physiol. Biochem., 2018, 51(2), 575-588.
[] [PMID: 30466099]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy