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Uselessness of Serum p53 Antibody for Detecting Colitis-associated Cancer in the Era of Immunosuppressive Therapy.

ABSTRACT: BACKGROUND/AIM:The present study examined the utility of serum p53 antibody (Ab) for detecting colitis-associated cancer (CAC) in the era of immunosuppressive therapy. PATIENTS AND METHODS:Two hundred and fifty patients were analyzed, 219 had no carcinoma or dysplasia (Group non-CAC), and 31 had carcinoma or dysplasia (Group CAC). Serum p53 Abs were detected with an enzyme-linked immunosorbent assay. Immunohistochemical detection was performed in Group CAC. RESULTS:Immunosuppressive therapy was performed in 98.1% of Group non-CAC and 80.6% of Group CAC. There were no differences in serum p53 Abs positivity between Groups non-CAC and CAC (8.7% vs. 3.2%, p=0.30). p53 staining positivity was noted in 90.3% of Group CAC, and the rate of serum p53 positivity was significantly lower in patients with immunosuppressive therapy than in those without in Group CAC (0.0% vs. 16.7%, p=0.04). CONCLUSION:The utility of serum p53 Ab for detecting CAC is dubious in the era of immunosuppressive therapy.

SUBMITTER: Toritani K

PROVIDER: S-EPMC7157871 | biostudies-literature | 2020 Mar-Apr

REPOSITORIES: biostudies-literature

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Uselessness of Serum p53 Antibody for Detecting Colitis-associated Cancer in the Era of Immunosuppressive Therapy.

Toritani Kenichiro K Kimura Hideaki H Kunisaki Reiko R Watanabe Jun J Kunisaki Chikara C Ishibe Atsushi A Chiba Sawako S Inayama Yoshiaki Y Endo Itaru I

In vivo (Athens, Greece) 20200301 2

<h4>Background/aim</h4>The present study examined the utility of serum p53 antibody (Ab) for detecting colitis-associated cancer (CAC) in the era of immunosuppressive therapy.<h4>Patients and methods</h4>Two hundred and fifty patients were analyzed, 219 had no carcinoma or dysplasia (Group non-CAC), and 31 had carcinoma or dysplasia (Group CAC). Serum p53 Abs were detected with an enzyme-linked immunosorbent assay. Immunohistochemical detection was performed in Group CAC.<h4>Results</h4>Immunosu ...[more]

PMID: 32111776

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Project description:The association between chronic inflammation and cancer has long been recognized. The inflammatory bowel disease ulcerative colitis frequently progresses to colon cancer; however, the underlying mechanism is still unclear. S100a9 has been emerged as an important pro-inflammatory mediator in acute and chronic inflammation, and the aberrant expression of S100a9 also contributes to tumorigenic processes such as cell proliferation, angiogenesis, metastasis, and immune evasion. We previously revealed that S100a8 and S100a9 are highly activated and play an important role in the process of colitis-associated carcinogenesis, which suggests an attractive therapeutic target for ulcerative colitis and related colon cancer. Here, we report that administration of a neutralizing anti-S100a9 antibody significantly ameliorated dextran sulfate sodium (DSS)-induced colitis and accompanied by diminished cellular infiltrate of innate immunity cells (macrophages, neutrophils, and dendritic cells) and production of pro-inflammatory cytokines (Tnf?, Il1?, Ifn?, Il6, Il17a, Il23a, Il4, and Il12a). The protective effect of anti-S100a9 antibody treatment was also observed in azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) mouse model. The inflammatory response, tumor cell proliferation, and immune cells infiltration in the colon tissues were suppressed by anti-S100a9 antibody. Gene expression profiling showed that key pathways known to be involved in CAC development, such as Wnt signaling pathway, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, and ECM-receptor interaction pathway, were suppressed after treatment with anti-S100a9 antibody in CAC mice. In view of the protective effect of neutralizing anti-S100a9 antibody against DSS-induced colitis and AOM/DSS-induced CAC in mouse model, this study suggests that anti-S100a9 antibody may provide a novel therapeutic approach to treat ulcerative colitis and may decrease the risk for developing CAC.

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Project description:BackgroundMutant p53 protein over-expression has been reported to induce serum antibodies against p53. We assessed the diagnostic precision of serum p53 (s-p53) antibodies for diagnosis of cancer patients and compared the positive rates of the s-p53 antibody in different types of cancers.MethodsWe systematically searched PubMed and Embase, through May 31, 2012. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and Area under the curve(AUC). Meta regression and subgroup analyses were done, and heterogeneity and publication bias were assessed.ResultsOf 1089 studies initially identified, 100 eligible studies with 23 different types of tumor met the inclusion criteria for the meta-analysis (cases = 15953, controls = 8694). However, we could conduct independent meta analysis on only 13 of 36 types of tumors. Approximately 56% (56/100) of the included studies were of high quality (QUADAS score≥8). The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of cancers were: PLR 5.75 (95% CI: 4.60-7.19), NLR 0.81 (95%CI: 0.79-0.83) and DOR 7.56 (95% CI: 6.02-9.50). However, for the 13 types of cancers on which meta-analysis was conducted, the ranges for PLR (2.33-11.05), NLR (0.74-0.97), DOR (2.86-13.80), AUC(0.29-0.81), and positive rate (4.47%-28.36%) indicated significant heterogeneity. We found that breast, colorectal, esophageal, gastric, hepatic, lymphoma, lung and ovarian cancer had relatively reasonable diagnostic accuracy. The remaining results of the five types of cancers suggested that s-p53 antibody had limited value.ConclusionsThe current evidence suggests that s-p53 antibody has potential diagnostic value for cancer, especially for breast, colorectal, esophageal, gastric, hepatic, lymphoma, lung and ovarian cancer. The results showed that s-p53 antibody had high correlation with cancers.

Dataset Information

Uselessness of Serum p53 Antibody for Detecting Colitis-associated Cancer in the Era of Immunosuppressive Therapy.

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Uselessness of Serum p53 Antibody for Detecting Colitis-associated Cancer in the Era of Immunosuppressive Therapy.

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