Dataset Information

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:BackgroundMutant p53 protein overexpression has been reported to induce serum antibodies against p53. Various studies assessing the diagnostic value of serum p53 antibody in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of serum p53 antibody in esophageal cancer.MethodsWe systematically searched PubMed and Embase until 31st May 2012, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). The PLR and NLR and their 95% confidence interval (CI) were calculated using a fixed effects model according to the Mantel-Haensed method and random effects model based on the work of Der Simonian and laird, respectively.ResultsFifteen studies (cases?=?1079, controls?=?2260) met the inclusion criteria for the meta-analysis. Approximately 53.33% (8/15) of the included studies were of high quality (QUADAS score?8), which were retrospective case-control studies. The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of esophageal cancer were PLR 6.95 (95% CI: 4.77-9.51), NLR 0.75 (95%CI: 0.72-0.78) and DOR 9.65 (95%CI: 7.04-13.22). However, we found significant heterogeneity between NLRs.ConclusionsThe current evidence suggests serum p53 antibody has a potential diagnostic value for esophageal cancer. However, its discrimination power is not perfect because of low sensitivity.ImpactThese results suggest that s-p53-antibody may be useful for monitoring residual tumor cells and for aiding in the selection of candidates for less invasive treatment procedures because of the high specificity of s-p53-antibody. Further studies may need to identify patterns of multiple biomarkers to further increase the power of EC detection.

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.

Project description:BACKGROUND:Current treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6?weeks of steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early SIT introduction and number of SIT infusions on clinical outcomes. METHODS:We performed a retrospective review of patients with IMC who received SIT at The University of Texas MD Anderson Cancer Center between January and December 2018. Logistic regression analyses were used to assess associations between clinical outcomes and features of IMC. RESULTS:Of the 1459 patients who received immune checkpoint inhibitors, 179 developed IMC of any grade; 84 of these 179 patients received SIT. Of the 84 patients who received SIT, 79% were males, and the mean age was 60?years (standard deviation, 14). Compared with patients who received SIT >?10?days after IMC onset, patients who received early SIT (?10?days) required fewer hospitalizations (P?=?0.03), experienced steroid taper failure less frequently (P?=?0.03), had fewer steroid tapering attempts (P?<?0.01), had a shorter course of steroid treatment (P?=?0.09), and had a shorter duration of symptoms (P?<?0.01). Patients who received one or two infusions of SIT achieved histologic remission less frequently (P?=?0.09) and had higher fecal calprotectin levels after SIT (P?=?0.01) compared with patients who received three or more infusions. Risk factors for IMC recurrence after weaning off steroids included: 1) needing multiple hospitalizations, 2) experiencing steroid taper failure after SIT, 3) receiving infliximab rather than vedolizumab, 4) receiving fewer than three infusions of SIT, 5) having higher fecal calprotectin levels after SIT, and 6) receiving a longer course of steroids, hospitalization and IMC symptoms. Unsuccessful weaning from steroids after SIT was associated with high IMC grades; multiple hospitalizations; steroid-resistant IMC; long interval from IMC to SIT initiation; and long duration of steroids, IMC symptoms, and hospitalization. CONCLUSION:SIT should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of SIT had more favorable clinical outcomes.

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.

Publications

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

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