Early diagnosis of colorectal cancer via plasma proteomic analysis of CRC and advanced adenomatous polyp
Gastroenterology and Hepatology from Bed to Bench,
Vol. 12 No. 4 (2019),
1 September 2019
,
Page 328-339
https://doi.org/10.22037/ghfbb.v12i4.1723
Abstract
Aim: This paper aimed to identify new candidate biomarkers in blood for early diagnosis of CRC.
Background: Colorectal cancer (CRC) is the third most widespread malignancies increasing globally. The high mortality rate associated with colorectal cancer is due to the delayed diagnosis in an advanced stage while the metastasis has occurred. For better clinical management and subsequently to reduce mortality of CRC, early detection biomarkers are in high demand.
Methods: A 2D-PAGE separation of proteins was performed followed by tandem mass Spectrometry (MALDI-TOF-TOF) to discover potential plasma protein markers for CRC and AA (advanced adenomas). Furthermore, western blot method was used to confirm a part of the results in colorectal tissue samples.
Results: The significantly altered proteins including HPR, HP, ALB, KRT1, APOA1, FGB, IGJ and C4A were down-regulated in polyp relative to normal, and CRC compare to polyp surprisingly, and inversely, ORM2 was up-regulated with the fold change ? 2 and p-value ? 0.05. We also surveyed APOA1, FGB, and C4A for further confirmation of their expression changes by western blotting. All three of them showed a decreasing trend from normal toward CRC tissue samples as it mentioned before, but just changes of FGB and C4A were significant.
Conclusion: The results demonstrated that plasma proteins can be less invasive markers for the detection of CRC. FGB and C4A can be considered as plasma potential biomarkers to early diagnosis of CRC patients and understanding the underlying procedures in tumorigenesis. Undoubtedly, the additional study must be conducted on large scale cohorts to verify the results.
Keywords: Colorectal cancer, Advanced adenomatous polyp, Early detection, Plasma biomarker, proteomics.
(Please cite as Fayazfar S, Zali H, Arefi Oskouie A, Asadzadeh Aghdaei H, Rezaei Tavirani M, Nazemalhosseini Mojarad E. Early diagnosis of colorectal cancer via plasma proteomic analysis of CRC and advanced adenomatous polyp. Gastroenterol Hepatol Bed Bench 2019;(4):328-339).
- Colorectal cancer (CRC)
- Advanced Adenomatous Polyp
- Early detection
- Plasma biomarker
- proteomics.
How to Cite
References
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin 2018;68:394-424.
Lee PY, Chin SF, Low TY, Jamal R. Probing the colorectal cancer proteome for biomarkers: Current status and perspectives. J Proteomics 2018;187:93-105.
Álvarez-Chaver P, Otero-Estévez O, de la Cadena MP, Rodríguez-Berrocal FJ, Martínez-Zorzano VS. Proteomics for discovery of candidate colorectal cancer biomarkers. World J Gastroenterol 2014;20:3804.
Arroyo R, Duran-Frigola M, Berenguer C, Soler-López M, Aloy P. Charting the molecular links between driver and susceptibility genes in colorectal cancer. Biochem Biophys Res Commun 2014;445:734-8.
Wisniewski JR, Dus-Szachniewicz K, Ostasiewicz P, Ziolkowski P, Rakus D, Mann M. Absolute Proteome Analysis of Colorectal Mucosa, Adenoma, and Cancer Reveals Drastic Changes in Fatty Acid Metabolism and Plasma Membrane Transporters. J Proteome Res 2015;14:4005-18.
Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar M, Mulrow C, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997;112:594-642.
Wolf AM, Fontham ET, Church TR, Flowers CR, Guerra CE, LaMonte SJ, et al. Colorectal cancer screening for average‐risk adults: 2018 guideline update from the American Cancer Society. Cancer J Clin 2018;68:250-81.
Carethers JM, Jung BH. Genetics and genetic biomarkers in sporadic colorectal cancer. Gastroenterology 2015;149:1177-90.
Kim DH, Pickhardt PJ, Taylor AJ. Characteristics of Advanced Adenomas Detected at CT Colonographic Screening: Implications for Appropriate Polyp Size Thresholds for Polypectomy Versus Surveillance. Am J Roentgenol 2007;188:940-4.
Zhai XH, Yu JK, Yang FQ, Zheng S. Identification of a new protein biomarker for colorectal cancer diagnosis. Mol Med Rep 2012;6:444-8.
Dillon R, Croner LJ, Bucci J, Kairs SN, You J, Beasley S, et al. Analytical validation of a novel multiplex test for detection of advanced adenoma and colorectal cancer in symptomatic patients. J Pharm Biomed Anal 2018;154:85-94.
Ward D, Suggett N, Cheng Y, Wei W, Johnson H, Billingham L, et al. Identification of serum biomarkers for colon cancer by proteomic analysis. Br J Cancer 2006;94:1898.
Doustjalali SR, Bhuiyan M, Al-Jashamy K, Linn NH, Abdul Kadir S, Appalanaidu V, et al. Two dimensional gel electrophoresis: An overview of proteomic technique in cancer research. Journal of Proteomics and Bioinformatics 2014;7:077-81.
Kuppusamy P, Govindan N, Yusoff MM, Ichwan SJA. Proteins are potent biomarkers to detect colon cancer progression. Saudi J Biol Sci 2017;24:1212-21.
Da Costa GG, Gomig THB, Kaviski R, Sousa KS, Kukolj C, De Lima RS, et al. Comparative proteomics of tumor and paired normal breast tissue highlights potential biomarkers in breast cancer. Cancer Genomics Proteomics 2015;12:251-61.
Gajbhiye A, Dabhi R, Taunk K, Vannuruswamy G, RoyChoudhury S, Adhav R, et al. Urinary proteome alterations in HER2 enriched breast cancer revealed by multipronged quantitative proteomics. Proteomics 2016;16:2403-18.
Akpinar G, Simsek T, Guler A, Kasap M, Canturk NZ. Elucidation of a conserved proteomic pattern of breast cancer tissue and metastatic axillary lymph node. Chirurgia 2017;112:443-8.
He J, Ma G, Qian J, Zhu Y, Liang M, Yao N, et al. Interaction between ezrin and cortactin in promoting epithelial to mesenchymal transition in breast cancer cells. Int Med J Exp Clin Res 2017;23:1583-96.
Zhan X, Yang H, Peng F, Li J, Mu Y, Long Y, et al. How many proteins can be identified in a 2DE gel spot within an analysis of a complex human cancer tissue proteome? Electrophoresis 2018;39:965-80.
Tsangaris GT, Dimas K, Malamou A, Katsafadou A, Papathanasiou C, Stravopodis DJ, et al. Molecular proteomic characterization of a pediatric medulloblastoma xenograft. Cancer Genomic Proteomic 2017;14:267-75.
Jain R, Atak A, Yeola A, Srivastava S. Proteomic level changes associated with S3I201 treated U87 glioma cells. J proteomics 2017;150:341-50.
Peng B, Lei N, Chai Y, Chan EK, Zhang JY. CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer. Mol Biosyst 2015;11:105-14.
Amin A, Bukhari S, Mokhdomi TA, Anjum N, Wafai AH, Wani Z, et al. Comparative proteomics and global genome-wide expression data implicate role of ARMC8 in lung cancer. Asian Pac J Cancer Prev 2015;16:3691-6.
Fan S, Xu Y, Li X, Tie L, Pan Y, Li X. Opposite angiogenic outcome of curcumin against ischemia and Lewis lung cancer models: in silico, in vitro and in vivo studies. Biochim Biophys Acta 2014;1842:1742-54.
Ayyub A, Saleem M, Fatima I, Tariq A, Hashmi N, Musharraf SG. Glycosylated Alpha-1-acid glycoprotein 1 as a potential lung cancer serum biomarker. Int J Biochem Cell Biol 2016;70:68-75.
Flores-Perez A, Marchat LA, Sanchez LL, Romero-Zamora D, Arechaga-Ocampo E, Ramirez-Torres N, et al. Differential proteomic analysis reveals that EGCG inhibits HDGF and activates apoptosis to increase the sensitivity of non-small cells lung cancer to chemotherapy. Proteomic Clin Appl 2016;10:172-82.
Giusti L, Iacconi P, Da Valle Y, Ciregia F, Ventroni T, Donadio E, et al. A proteomic profile of washing fluid from the colorectal tract to search for potential biomarkers of colon cancer. Mol Biosyst 2012;8:1088-99.
Baek JY, Yeo HY, Chang HJ, Kim KH, Kim SY, Park JW, et al. Serpin B5 is a CEA-interacting biomarker for colorectal cancer. Int J Cancer 2014;134:1595-604.
Liu W, Ma Y, Huang L, Peng J, Zhang P, Zhang H, et al. Identification of HSP27 as a potential tumor marker for colorectal cancer by the two-dimensional polyacrylamide gel electrophoresis. Mol Biol Rep 2010;37:3207-16.
Vieira de Ribeiro AJ, Sandim V, Ornellas AA, Reis RS, Domont G, Alves G. Differencial proteome of clear-cell renal cell carcinoma (ccRCC) tissues. Int Braz J Urol 2013;39:83-94.
Vasudev NS, Ferguson RE, Cairns DA, Stanley AJ, Selby PJ, Banks RE. Serum biomarker discovery in renal cancer using 2-DE and prefractionation by immunodepletion and isoelectric focusing; increasing coverage or more of the same? Proteomics 2008;8:5074-85.
Kim DS, Choi YP, Kang S, Gao MQ, Kim B, Park HR, et al. Panel of candidate biomarkers for renal cell carcinoma. J Proteome Res 2010;9:3710-9.
Sandim V, Pereira Dde A, Kalume DE, Oliveira-Carvalho AL, Ornellas AA, Soares MR, et al. Proteomic analysis reveals differentially secreted proteins in the urine from patients with clear cell renal cell carcinoma. Urol Oncol 2016;34:e11-25.
Li M, Yin J, Mao N, Pan L. Upregulation of phosphorylated cofilin 1 correlates with taxol resistance in human ovarian cancer in vitro and in vivo. Oncol Rep 2013;29:58-66.
Ahmed N, Barker G, Oliva KT, Hoffmann P, Riley C, Reeve S, et al. Proteomic-based identification of haptoglobin-1 precursor as a novel circulating biomarker of ovarian cancer. Br J Cancer 2004;91:129-40.
Liu XX, Ye H, Wang P, Li LX, Zhang Y, Zhang JY. Proteomic-based identification of HSP70 as a tumor-associated antigen in ovarian cancer. Oncol Rep 2017;37:2771-8.
Lorkova L, Pospisilova J, Lacheta J, Leahomschi S, Zivny J, Cibula D, et al. Decreased concentrations of retinol-binding protein 4 in sera of epithelial ovarian cancer patients: a potential biomarker identified by proteomics. Oncol Rep 2012;27:318-24.
Di Michele M, Marcone S, Cicchillitti L, Della Corte A, Ferlini C, Scambia G, et al. Glycoproteomics of paclitaxel resistance in human epithelial ovarian cancer cell lines: towards the identification of putative biomarkers. J Proteomics 2010;73:879-98.
Dehghan-Nayeri N, Eshghi P, Pour KG, Rezaei-Tavirani M, Omrani MD, Gharehbaghian A. Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia. Cancer Chemother Pharmacol 2017;80:177-85.
Tripathi S, Kumar YB, Agrawal A, Prabhakar A, Joshi SS. Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects. Sci Rep 2016;6:26749.
Lim LC, Looi ML, Zakaria SZS, Sagap I, Rose IM, Chin SF, et al. Identification of differentially expressed proteins in the serum of colorectal cancer patients using 2D-DIGE proteomics analysis. Pathol Oncol Res 2016;22:169-77.
Kuhajda FP, Piantadosi S, Pasternack GR. Haptoglobin-related protein (Hpr) epitopes in breast cancer as a predictor of recurrence of the disease. New Engl J Med 1989;321:636-41.
Wang Q, Yu Q, Lin Q, Duan Y. Emerging salivary biomarkers by mass spectrometry. Clin Chim Acta 2015;438:214-21.
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009;4:44-57.
Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatic 2016;54:1.30.
Bresalier RS, Byrd JC, Tessler D, Lebel J, Koomen J, Hawke D, et al. A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer. Gastroenterology 2004;127:741-8.
Li J, Tian W, Liu X, Hu S, Zhang B, Li X. [Screening and mass spectrometry analysis of differentially expressed proteins of plasm between laryngocarcinoma and healthy individuals]. J Clin Otorhinolaryngol 2013;27:771-4.
Ghuman S, Van Hemelrijck M, Garmo H, Holmberg L, Malmstrom H, Lambe M, et al. Serum inflammatory markers and colorectal cancer risk and survival. Br J Cancer 2017;116:1358-65.
Sun L, Hu S, Yu L, Guo C, Sun L, Yang Z, et al. Serum haptoglobin as a novel molecular biomarker predicting colorectal cancer hepatic metastasis. Int J Cancer 2016;138:2724-31.
Sun L, Pan J, Peng L, Fang L, Zhao X, Sun L, et al. Combination of haptoglobin and osteopontin could predict colorectal cancer hepatic metastasis. Ann Surg Oncol 2012;19:2411-9.
Dowling P, Clarke C, Hennessy K, Torralbo-Lopez B, Ballot J, Crown J, et al. Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer. Int J Cancer 2012;131:911-23.
Milano G, Cooper EH, Goligher JC, Giles GR, Neville AM. Serum prealbumin, retinol-binding protein, transferrin, and albumin levels in patients with large bowel cancer. J Natl Cancer Inst 1978;61:687-91.
Shibutani M, Maeda K, Nagahara H, Iseki Y, Ikeya T, Hirakawa K. Prognostic significance of the preoperative ratio of C-reactive protein to albumin in patients with colorectal cancer. Anticancer Res 2016;36:995-1001.
Boonpipattanapong T, Chewatanakornkul S. Preoperative carcinoembryonic antigen and albumin in predicting survival in patients with colon and rectal carcinomas. J Clin Gastroenterol 2006;40:592-5.
Dixon MR, Haukoos JS, Udani SM, Naghi JJ, Arnell TD, Kumar RR, et al. Carcinoembryonic antigen and albumin predict survival in patients with advanced colon and rectal cancer. Arch Surg 2003;138:962-6.
Liu Y, Chen S, Zheng C, Ding M, Zhang L, Wang L, et al. The prognostic value of the preoperative c-reactive protein/albumin ratio in ovarian cancer. BMC Cancer 2017;17:285.
Kakazu E, Kondo Y, Kogure T, Ninomiya M, Kimura O, Iwata T, et al. Supplementation of branched-chain amino acids maintains the serum albumin level in the course of hepatocellular carcinoma recurrence. Tohoku J Exp Med 2013;230:191-6.
Soudy R, Etayash H, Bahadorani K, Lavasanifar A, Kaur K. Breast cancer targeting peptide binds keratin 1: a new molecular marker for targeted drug delivery to breast cancer. Mol Pharm 2017;14:593-604.
Blanckaert V, Kerviel V, Lepinay A, Joubert-Durigneux V, Hondermarck H, Chenais B. Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1. Int J Oncol 2015;46:2649-55.
Tang S, Huang W, Zhong M, Yin L, Jiang H, Hou S, et al. Identification Keratin 1 as a cDDP-resistant protein in nasopharyngeal carcinoma cell lines. J Proteomics 2012;75:2352-60.
Wang Y, Wang ZQ, Wang FH, Lei XF, Yan SM, Wang DS, et al. Predictive value of chemotherapy-related high-density lipoprotein cholesterol (HDL) elevation in patients with colorectal cancer receiving adjuvant chemotherapy: an exploratory analysis of 851 cases. Oncotarget 2016;7:57290-300.
Chandler PD, Song Y, Lin J, Zhang S, Sesso HD, Mora S, et al. Lipid biomarkers and long-term risk of cancer in the Women's Health Study. Am J Clin Nutr 2016;103:1397-407.
Borgquist S, Butt T, Almgren P, Shiffman D, Stocks T, Orho-Melander M, et al. Apolipoproteins, lipids and risk of cancer. Int J Cancer 2016;138:2648-56.
Cine N, Baykal AT, Sunnetci D, Canturk Z, Serhatli M, Savli H. Identification of ApoA1, HPX and POTEE genes by omic analysis in breast cancer. Oncol Rep 2014;32:1078-86.
Liu X, Zheng W, Wang W, Shen H, Liu L, Lou W, et al. A new panel of pancreatic cancer biomarkers discovered using a mass spectrometry-based pipeline. Br J Cancer 2017;117:1846-54.
Zhao J, Cheng W, He X, Liu Y, Li J, Sun J, et al. Construction of a specific SVM classifier and identification of molecular markers for lung adenocarcinoma based on lncRNA-miRNA-mRNA network. Onco Targets Ther 2018;11:3129-40.
Zhang C, Leng W, Sun C, Lu T, Chen Z, Men X, et al. Urine proteome profiling predicts lung cancer from control cases and other tumors. EBioMedicine 2018;30:120-8.
Repetto O, Maiero S, Magris R, Miolo G, Cozzi MR, Steffan A, et al. Quantitative Proteomic Approach Targeted to Fibrinogen beta Chain in Tissue Gastric Carcinoma. Int J Mol Sci 2018;19.
Linden M, Segersten U, Runeson M, Wester K, Busch C, Pettersson U, et al. Tumour expression of bladder cancer-associated urinary proteins. BJU Int 2013;112:407-15.
Wang Y, Shan Q, Hou G, Zhang J, Bai J, Lv X, et al. Discovery of potential colorectal cancer serum biomarkers through quantitative proteomics on the colonic tissue interstitial fluids from the AOM-DSS mouse model. J Proteomics 2016;132:31-40.
Hoffmann K, Firth MJ, Beesley AH, Freitas JR, Ford J, Senanayake S, et al. Prediction of relapse in paediatric pre-B acute lymphoblastic leukaemia using a three-gene risk index. Br J Hematol 2008;140:656-64.
Zhi H, Zhang J, Hu G, Lu J, Wang X, Zhou C, et al. The deregulation of arachidonic acid metabolism‐related genes in human esophageal squamous cell carcinoma. Int J Cancer 2003;106:327-33.
Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC. Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res 2009;11:R7.
Zhu D, Zhong Y, Wu H, Ye L, Wang J, Li Y, et al. Predicting metachronous liver metastasis from colorectal cancer using serum proteomic fingerprinting. J Surg Res 2013;184:861-6.
Kim H, Kim K, Yu SJ, Jang ES, Yu J, Cho G, et al. Development of biomarkers for screening hepatocellular carcinoma using global data mining and multiple reaction monitoring. PloS One 2013;8:e63468.
Ornellas P, Ornellas AA, Chinello C, Gianazza E, Mainini V, Cazzaniga M, et al. Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis. Int Braz J Urol 2012;38:739-49.
Gao F, Zhang X, Whang S, Zheng C. Prognostic impact of plasma ORM2 levels in patients with stage II colorectal cancer. Ann Clin Lab Sci 2014;44:388-93.
Zhang X, Xiao Z, Liu X, Du L, Wang L, Wang S, et al. The potential role of ORM2 in the development of colorectal cancer. PloS One 2012;7:e31868.
Rucksaken R, Charoensuk L, Pinlaor P, Pairojkul C, Khuntikeo N, Pinlaor S. Plasma orosomucoid 2 as a potential risk marker of cholangiocarcinoma. Cancer Biomarker 2017:1-8.
Fang T, Cui M, Sun J, Ge C, Zhao F, Zhang L, et al. Orosomucoid 2 inhibits tumor metastasis and is upregulated by CCAAT/enhancer binding protein β in hepatocellular carcinomas. Oncotarget 2015;6:16106.
Rucksaken R, Khoontawad J, Roytrakul S, Pinlaor P, Hiraku Y, Wongkham C, et al. Proteomic analysis to identify plasma orosomucoid 2 and kinesin 18A as potential biomarkers of cholangiocarcinoma. Cancer Biomarker 2013;12:81-95.
Duché JC, Urien S, Simon N, Malaurie E, Monnet I, Barré J. Expression of the genetic variants of human alpha-1-acid glycoprotein in cancer. Clin Biochem 2000;33:197-202.
Siegerink B, Rosendaal FR, Algra A. Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke. J Thromb Haemost 2009;7:385-90.
Vu D, Bolton-Maggs PH, Parr JR, Morris MA, de Moerloose P, Neerman-Arbez M. Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion. Blood 2003;102:4413-5.
Wojtukiewicz MZ, Zacharski LR, Memoli VA, Kisiel W, Kudryk BJ, Rousseau SM, et al. Indirect activation of blood coagulation in colon cancer. Thromb Haemost 1989;62:1062-6.
Tan Z, Zhang M, Han Q, Wen J, Luo K, Lin P, et al. A novel blood tool of cancer prognosis in esophageal squamous cell carcinoma: the Fibrinogen/Albumin Ratio. J Cancer 2017;8:1025-9.
Lin Y, Liu Z, Qiu Y, Zhang J, Wu H, Liang R, et al. Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2018;44:1494-503.
Troppan KT, Melchardt T, Wenzl K, Schlick K, Deutsch A, Bullock MD, et al. The clinical significance of fibrinogen plasma levels in patients with diffuse large B cell lymphoma. J Clin Pathol 2016;69:326-30.
Lu ZL, Chen YJ, Jing XY, Wang NN, Zhang T, Hu CJ. Detection and Identification of Serum Peptides Biomarker in Papillary Thyroid Cancer. Int Med J Exp Clin Res 2018;24:1581-7.
Kolodziejczyk J, Ponczek MB. The role of fibrinogen, fibrin and fibrin(ogen) degradation products (FDPs) in tumor progression. Contemp Oncol (Pozn) 2013;17:113-9.
Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 2012;34:43-62.
Mitter C, Zielinski C. Plasma levels of D-dimer: a crosslinked fibrin-degradation product in female breast cancer. J Cancer Res Clin Oncol 1991;117:259-62.
Repetto O, Maiero S, Magris R, Miolo G, Cozzi M, Steffan A, et al. Quantitative proteomic approach targeted to fibrinogen β chain in tissue gastric carcinoma. Int J Mol Sci 2018;19:759.
Schäfer M, Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 2008;9:628.
Falus A, Kramer J, Walcz E, Varga Z, Setalo J, Jobst K, et al. Unequal expression of complement C4A and C4B genes in rheumatoid synovial cells, human monocytoid and hepatoma-derived cell lines. Immunology 1989;68:133-6.
Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest 2017;127:780-9.
Pio R. Control of complement activation by cancer cells and its implications in antibody-mediated cancer immunotherapy. Inmunology 2006;25:173-87.
Pio R, Corrales L, Lambris JD. The role of complement in tumor growth. Adv Exp Med Biol 2014;772:229-62.
Taneja S, Ahmad I, Sen S, Kumar S, Arora R, Gupta VK, et al. Plasma peptidome profiling of acute hepatitis E patients by MALDI-TOF/TOF. Proteome Sci 2011;9:5.
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