ENZYME-LINKED IMMUNOSORBENT ASSAY DETECTION FOR MALIGNANCY USING ANTI-P53 ANTIBODIES
Tumour protein 53 (p53) plays an important role in the instruction of the cell cycle. In a variety of transformed cell lines, tumour protein is expressed in high amounts, and it is believed to contribute to transformation and malignancy. This research aimed to detect the anti-p53 antibodies in sera of patients with various malignant tumours and to evaluate the sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA). A case-control study was conducted on samples from 49 patients with various types of malignant tumours at Sultanah Bahiyah Hospital, Alor Setar, Kedah, Malaysia, and 32 healthy control cases with non‐malignant disease collected from Universiti Sains Malaysia clinic, Penang, Malaysia. The antibodies against p53 protein in the serum samples were analysed using the commercial ELISA kit, Calbiochem® p53- ELISAPLUS. The results showed that the rate of anti-p53 antibodies in patients with various malignant tumours was 13 out of 49 (26.5 %), compared with only 2 out of 32 (6.25%) in healthy controls (p < 0.001). The sensitivity of this kit reached 28.6% and the specificity was 93.8%. In conclusion, these results suggest that the anti-p53 antibodies can be detected in different sera of malignant tumour patients and the ELISA kit is highly specific; nevertheless, its discrimination power is not perfect because of its low sensitivity to determine the anti-p53 antibodies.
Yue X, Zhao Y, Xu Y, Zheng M, Feng Z, Hu W. Mutant p53 in cancer: accumulation, gain-of-function, and therapy. J Mol Biol 2017; 429(11):1595-606.
Flórez M, Fêo HB, Da Silva G, Yamatogi RS, Aguiar A, Araújo Jr J, et al. Cell cycle kinetics, apoptosis rates and gene expressions of MDR‐1, TP53, BCL‐2 and BAX in transmissible venereal tumour cells and their association with therapy response. Vet Comp Oncol 2017; 15(3):793-807.
Katano H. Pathological Features of Kaposi’s Sarcoma-Associated Herpesvirus Infection. Adv Exp Med Biol 2018; 1045:357-376.
Chen J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harb. Perspect Med 2016; 6(3):a026104.
Walia S, Kamal R, Dhawan D, Kanwar S. Chemoprevention by probiotics during 1, 2-dimethylhydrazine-induced colon carcinogenesis in rats. Dig Dis Sci 2018; 63(4):900-9.
Kearney JF, Patel P, Stefanov EK, King RG. Natural antibody repertoires: development and functional role in inhibiting allergic airway disease. Annu Rev Immunol 2015; 33:475-504.
Koneczny I, Herbst R. Myasthenia gravis: pathogenic effects of autoantibodies on neuromuscular architecture. Cells 2019; 8(7):671.
AbuSara NF, Piercey BM, Moore MA, Shaikh AA, Nothias L-F, Srivastava SK, et al. Comparative genomics and metabolomics analyses of clavulanic acid-producing Streptomyces species provides insight into specialized metabolism. Front Microbiol 2019; 10:2550.
Yu G, Luo H, Zhang N, Wang Y, Li Y, Huang H, et al. Loss of p53 sensitizes cells to palmitic acid-induced apoptosis by reactive oxygen species accumulation. Int J Mol Sci 2019; 20(24):6268.
Shimada H. p53 molecular approach to diagnosis and treatment of esophageal squamous cell carcinoma. Ann. Gastroenterol. Ann Gastroenterol Surg 2018; 2(4):266-73.
Fierabracci A, Pellegrino M. The double role of p53 in cancer and autoimmunity and its potential as therapeutic target. Int J Mol Sci 2016; 17(12):1975.
Blanchard P, Quero L, Pacault V, Schlageter M-H, Baruch-Hennequin V, Hennequin C. Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy. BMC cancer 2012; 12(1):119.
Sorrell AD, Espenschied CR, Culver JO, Weitzel JN. Tumor protein p53 (TP53) testing and Li-Fraumeni syndrome. Mol Diagn Ther 2013; 17(1):31-47.
Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, et al. A systematic p53 mutation library links differential functional impact to cancer mutation pattern and evolutionary conservation. Mol Cell 2018; 71(1):178-90. e8.
Suppiah, A., A. Alabi, L. Madden, J. Hartley, J. Monson and J. Greenman. "Anti-p53 autoantibody in colorectal cancer: prognostic significance in long-
Malaysian Journal of Public Health Medicine 2021, Vol 21 (1): 208-215
term follow-up. Int J Colorectal Dis 2008; 23(6): 595-600.
Leo O, Cunningham A, Stern PL. Vaccine immunology. Perspectives in Vaccinology 2011; 1(1):25-59.
Suzuki T, Yajima S, Ishioka N, Nanami T, Oshima Y, Washizawa N, et al. Prognostic significance of high serum p53 antibody titers in patients with esophageal squamous cell carcinoma. Esophagus 2018; 15(4):294-300.
Byun DJ, Wolchok JD, Rosenberg LM, Girotra M. Cancer immunotherapy—immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol 2017; 13(4):195-207.
Kim MP, Lozano G. Mutant p53 partners in crime. Cell Death Differ 2018; 25(1):161-8.
Bykov VJ, Eriksson SE, Bianchi J, Wiman KG. Targeting mutant p53 for efficient cancer therapy. Nat Rev Cancer 2018; 18(2):89.
Ushigome M, Nabeya Y, Soda H, Takiguchi N, Kuwajima A, Tagawa M, et al. Multi-panel assay of serum autoantibodies in colorectal cancer. Int J Clin Oncol 2018; 23(5):917-23.
Áyen Á, Jiménez Martínez Y, Marchal JA, Boulaiz H. Recent progress in gene therapy for ovarian cancer. Int J Mol Sci 2018; 19(7):1930.
Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun 2018; 9(1):1-7.
Crawford, L., D. Pim and R. Bulbrook. Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer 1982; 30(4): 403-408.
Jabir FA, Hoidy WH. No Evaluation of Serum P53 Levels in Iraqi Female Breast Cancer Patients. Asian Pac J Cancer Prev 2017; 18(9):255.
Sangrajrang S, Arpornwirat W, Cheirsilpa A, Thisuphakorn P, Kalalak A, Sornprom A, et al. Serum p53 antibodies in correlation to other biological parameters of breast cancer. Cancer Detect Prev 2003; 27(3):182-6.
Okada R, Shimada H, Otsuka Y, Tsuchiya M, Ishii J, Katagiri T, et al. Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma. Surgery Today 2017; 47(12):1492-9.
Peyrat J-P, Fournier J, Bonneterre J, Vanlemmens L, Lubin R, Soussi T et al. Prognostic significance of circulating p53 antibodies in patients undergoing surgery for locoregional breast cancer. The Lancet 1995; 345(8950):621-2.
Wang W, Qin J-J, Voruganti S, Srivenugopal KS, Nag S, Patil S, et al. The pyrido [b] indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models. Nat Commun 2014; 5(1):1-12.
Okada R, Otsuka Y, Wakabayashi T, Shinoda M, Aoki T, Murakami M, et al. Six autoantibodies as potential serum biomarkers of hepatocellular carcinoma: A prospective multicenter study. Int J Cancer 2020; 147(9):2578-86.
Hoshino I, Nagata M, Takiguchi N, Nabeya Y, Ikeda A, Yokoi S, et al. Panel of autoantibodies against multiple tumor‐associated antigens for detecting gastric cancer. Cancer Science 2017; 108(3):308-15.
Takashi S, Satoshi Y, Akihiko O, Naoya Y, Yusuke T, Kentaro M, et al. Clinical impact of preoperative serum p53 antibody titers in 1487 patients with surgically treated esophageal squamous cell carcinoma: a multi-institutional study. Esophagus 2020:1-7. doi: 10.1007/s10388-020-00761-6.
Mattioni, M., S. Soddu, A. Prodosmo, P. Visca, S. Conti, G. Alessandrini, F. Facciolo and L. Strigari. Prognostic role of serum p53 antibodies in lung cancer. BMC cancer 2015; 15(1): 148.
Shiratori F, Ito M, Yajima S, Suzuki T, Oshima Y, Nanami T, et al. The effectiveness of serum midkine in detecting esophageal squamous cell carcinoma. Esophagus 2019; 16(3):246-51.
Shimada H, Ochiai T, Nomura F. Titration of serum p53 antibodies in 1085 patients with various types of malignant tumors: a multiinstitutional analysis by the Japan p53 Antibody Research Group. Interdisciplinary International Journal of the American Cancer Society 2003; 97(3):682-9.
Malaysian Journal of Public Health Medicine 2021, Vol 21 (1): 208-215
Lubin R, B Schlichtholz, JLTeillaud, E Garay, A Bussel, CP Wild, et al. p53 antibodies in patients with various types of cancer: assay, identification, and characterization. Clin Cancer Res 1995; 1:1463–9.
Chang Y, Liu B, Niu H, Wang Z, Xia S, Li H. Value of anti-p53 antibody as a biomarker for hepatocellular carcinoma: Evidence from a meta-analysis. Medicine 2020; 99(34).e21887.
Pedersen J, Gentry-Maharaj A, Fourkala E, Dawnay A, Burnell M, Zaikin A, et al. Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer. Br J Cancer 2013; 108(1):107-14.