P53 Autoantibodies Research Articles

Assaying of p53 Autoantibodies in saliva for the detection of oral squamous cell carcinoma. A road not taken.

Autoantibody detection is a promising approach to cancer screening. Serum p53 antibodies have been time tested in various cancers, including oral squamous cell carcinoma (OSCC). This study is aimed to detect and determine the level of p53 autoantibodies (p53-AAbs) in saliva. The association of clinicopathological features among patients with and without OSCC was also explored as a novel method for the detection of autoantibodies. One hundred preoperative saliva samples from patients with histologically confirmed OSCC and a hundred from normal healthy individuals were collected. Anti p53 detection kit assessed levels of salivary p53-AAbs. The cut-off value was 1.3 U/mL by Enzyme-linked immunosorbent assay (ELISA). The p53-AAb levels were expressed in terms of the median and interquartile range (IQR). Fischer's exact test and Chi-square test were used to determine the association with clinicopathological features among patients with OSCC and healthy controls with tobacco consumption habits. Median level of p53-AAb is 0.234 U/mL (IQR 0.18-0.37U/mL) in healthy controls and 0.285U/mL (IQR 0.16-0.58U/mL) in OSCC. p53-AAbs was positive in 15% of 100 patients with OSCC, which was statistically higher (P < 0.001) among OSCC, and controls were negative for p53-AAb. No significant correlation of p53-AAbs with the patient's age, gender, site, clinical staging (TNM), and pathologic grade was observed. However, a significant association was seen between the node involvement and salivary p53-AAbs. Salivary p53-AAb positivity was seen in a higher proportion in OSCC patients than in healthy controls with tobacco consumption, and the levels did differ significantly among OSCC and healthy controls.

B-360 Usefulness of the Ratios of CYFRA21-1 and p53 Autoantibody Immune Complexes to Their Free Antigens in Lung Cancer

Abstract Background Autoantibodies against specific cancer-associated antigens are produced in the early stages of tumorigenesis. In lung cancer, the possibility of autoantibodies as diagnostic biomarkers has been proposed. This study was to evaluate the usefulness of novel DNA-guided sandwich immunoassay detecting CYFRA21-1 and p53 autoantibody immune complexes and their free antigens in diagnosis of lung cancer. Methods In total, 100 patients with lung cancer and 119 healthy controls were analyzed with 9G testTM Lung/Cancer (Biometrix Technology, South Korea) measuring plasma autoantibody immune complexes (CYFRA21-1 with anti-CYFRA21-1 autoantibody immune complex (CIC), p53 with anti-p53 autoantibody immune complex (PIC)) and their free antigens (CYFRA 21-1 and p53). The ratios of CIC to CYFRA21-1 (CIC/CYFRA21-1) and PIC to p53 (PIC/p53), and the multiplication of the two ratios, named as LC index were calculated. Results The levels of CIC and PIC were significantly increased in lung cancer compared with those in healthy control (P = 0.0062 and P = 0.0026, respectively), while free antigens didn’t distinguish between lung cancer and healthy control. The ratios CIC/CYFRA21-1 and PIC/p53 were significantly higher in lung cancer than those in healthy control (all, P &amp;lt; 0.0001). Diagnostic performances expressed as area under the curve (AUC) were higher in the ratios of autoantibody immune complexes to each free antigen (PIC/p53 and CIC/CYFRA21-1) than autoantibody immune complexes (PIC and CIC) (AUC; 0.887, 0.847 vs 0.618, 0.608, respectively). The most excellent diagnostic performance was proven with LC index at diagnostic cut-off 3.60, which showed 81% sensitivity and 95% specificity with 0.945 AUC (P &amp;lt; 0.001). It was more sensitive to early lung cancer than to advanced lung cancer (sensitivity 87.5% vs 72.7%). Conclusion The ratios of CIC to CYFRA21-1 and PIC to p53 are useful biomarkers in lung cancer diagnosis and the combination of the ratios, LC index could be complementary tool for lung cancer screening with radiological tests.

Amyloid-like p53 as prognostic biomarker in serous ovarian cancer-a study of the OVCAD consortium.

TP53 is the most commonly mutated gene in cancer and has been shown to form amyloid-like aggregates, similar to key proteins in neurodegenerative diseases. Nonetheless, the clinical implications of p53 aggregation remain unclear. Here, we investigated the presence and clinical relevance of p53 aggregates in serous ovarian cancer (OC). Using the p53-Seprion-ELISA, p53 aggregates were detected in 46 out of 81 patients, with a detection rate of 84.3% in patients with missense mutations. High p53 aggregation was associated with prolonged progression-free survival. We found associations of overall survival with p53 aggregates, but they did not reach statistical significance. Interestingly, p53 aggregation was significantly associated with elevated levels of p53 autoantibodies and increased apoptosis, suggesting that high levels of p53 aggregates may trigger an immune response and/or exert a cytotoxic effect. To conclude, for the first time, we demonstrated that p53 aggregates are an independent prognostic marker in serous OC. P53-targeted therapies based on the amount of these aggregates may improve the patient's prognosis.

Au-Loaded Superparamagnetic Mesoporous Bimetallic CoFeB Nanovehicles for Sensitive Autoantibody Detection.

Construction of a well-defined mesoporous nanostructure is crucial for applying nonnoble metals in catalysis and biomedicine owing to their highly exposed active sites and accessible surfaces. However, it remains a great challenge to controllably synthesize superparamagnetic CoFe-based mesoporous nanospheres with tunable compositions and exposed large pores, which are sought for immobilization or adsorption of guest molecules for magnetic capture, isolation, preconcentration, and purification. Herein, a facile assembly strategy of a block copolymer was developed to fabricate a mesoporous CoFeB amorphous alloy with abundant metallic Co/Fe atoms, which served as an ideal scaffold for well-dispersed loading of Au nanoparticles (∼3.1 nm) via the galvanic replacement reaction. The prepared Au-CoFeB possessed high saturation magnetization as well as uniform and large open mesopores (∼12.5 nm), which provided ample accessibility to biomolecules, such as nucleic acids, enzymes, proteins, and antibodies. Through this distinctive combination of superparamagnetism (CoFeB) and biofavorability (Au), the resulting Au-CoFeB was employed as a dispersible nanovehicle for the direct capture and isolation of p53 autoantibody from serum samples. Highly sensitive detection of the autoantibody was achieved with a limit of detection of 0.006 U/mL, which was 50 times lower than that of the conventional p53-ELISA kit-based detection system. Our assay is capable of quantifying differential expression patterns for detecting p53 autoantibodies in ovarian cancer patients. This assay provides a rapid, inexpensive, and portable platform with the potential to detect a wide range of clinically relevant protein biomarkers.

Pre-diagnostic circulating p53 autoantibodies and subsequent lung cancer risk in low-income African and European Americans

IntroductionMutations of the TP53 gene lead to the production of autoantibodies against p53, a major tumor suppressor protein. Although studies have indicated the association of p53 autoantibodies with human cancers, epidemiologic evidence on lung cancer is still lacking. MethodsIn this nested case-control study conducted within the Southern Community Cohort Study, we investigated the association of circulating p53 autoantibodies with the subsequent risk of developing lung cancer. Using blood samples collected prior to any cancer diagnosis from 295 cases and their individually matched controls, seroreactivity to p53 was assessed by fluorescent bead-based multiplex serology. Conditional logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for lung cancer risk associated with p53 autoantibodies. ResultsAfter adjustment for potential confounders, p53 seropositivity was significantly associated with an increased risk of lung cancer (OR=2.98, 95 % CI: 1.10–8.06) among African Americans, but not among European Americans (OR=1.21, 95 % CI: 0.24–6.15). The positive associations were restricted to men (OR=4.59, 95 % CI: 1.30–16.16) and participants with a short interval (≤ 4 years) from blood collection to diagnosis (OR=4.30, 95 % CI: 1.33–13.89). ConclusionOur findings add to the evidence supporting p53 autoantibodies as a biomarker of lung cancer.

Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis

BackgroundThe increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques especially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity.MethodsA diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP, and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings.ResultsA total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1, and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2, and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10 and 56%, the panel sensitivity values reported across studies were higher with an estimated range of 60–87%.ConclusionFindings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2, and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.

Plasma biomarkers: new non-invasive tests in the early diagnosis of colorectal cancer?

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States and Europe. In Peru, it ranks fourth for both incidence and mortality. Colonoscopy is the gold standard for screening tests, showing high sensitivity and specificityto identify polyps and cancer (&gt; 98 %). However, it is an invasive procedure, which should be repeated at certain intervals, is expensive, and has low compliance rates and a perforation risk of 1 per 1,000 to 10,000. These limitations make it useless as an early detection tool in terms of implementation costs in many countries. An alternative is the use of plasma tumor biomarkers, which are molecular products metabolized and secreted by neoplastic tissue. These tests are based on proteins or nucleic acids,and represent a tool for the early detection, prognosis, survival and prediction of the response to CRC treatment. The objective of this research work is to analyze the usefulness of protein-based plasma biomarkers for the early detection of CRC. Moreover,a combination of biomarkers that includes carcinoembryonic antigen, cyclooxygenase 2, tissue inhibitor of metalloproteinase-1 and p53 autoantibodies is proposed to maximize the benefits of early detection of premalignant lesions and colorectal cancer, and minimize the number of patients with false-positive results and invasive procedures with potential complications.

P53 Gene Mutation Associated With Worse Clinicopathological Characteristic in Breast Cancer

Background: P53 is a tumour suppresor gene. In breast cancer, p53 gene mutation were noted with frequency of about 30% (range 15 to 71%) and associated with poor prognosis. This study was performed to determine p53 mutation association with clinicopathological characteristic in breast cancer and to assess the suitability of patients’ serum to detect p53 autoantibody. Methods: This study conducted in Hospital Seberang Jaya and Institut Perubatan dan Pergigian Termaju, Universiti Sains Malaysia. Sixty-four breast cancer patients with available fresh breast cancer tissue that been kept under -80°C and with complete clinicopathological, data involve in this study. These fresh breast tissues DNA extracted and 10sampels sent for DNA sequencing. The remaining 54samples proceeded with Polymerase Chains Reaction analysis based on the result from DNA sequencing. The serum of these patients was also taken for p53 autoantibody study using ELISA method. Results: The mean age of the patients in this study was 52.45±9.51 yrs. Most of the patients were Malay with 67.2% followed by Indian and Chinese with 17.2% and 15.6% respectively. 51.6%, of these patients undergone CT scan staging and 14.1% has distant metastases. p53 gene mutation prevalence showed rs1042522 only has 15.7% mutation. There was 54.7% Deletion A and 45.3% Wild Type A detected in rs59758982, 87.5% Deletion A and 12.5% Wild Type A in rs35069695 and 92.2 % recorded for Deletion GAA in rs376546152. There was no significant result between these mutation with breast cancer molecular classification and breast cancer aggressiveness except for rs59758982 shows significant result with p value 0.04 (p &lt;0.05). In regards on for p53 serum autoantibodies, 20.3% of the patients noted to be positive but it has no significant association with p53 gene mutations. Conclusion: In this study, tissue p53 genetic mutation has no significant association with clinicopathological characteristic of breast cancer and the use of serum p53 autoantibody as biomarkers is inconclusive.

The role of autoantibody detection in the diagnosis and staging of lung cancer.

BackgroundPreviously, the clinical value of seven autoantibodies (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1, and CAGE) has been surveyed in our pilot observation and other published studies. Herein, we aimed to further investigate the role of these autoantibodies in the diagnosis and staging of LC.MethodsWe included a total of 135 individuals, who were divided into a Lung cancer (LC) group and a control group according to the final diagnosis. Seven autoantibody detection kits were used (ELISA method) for the expression measurement. The patients’ demographics information (e.g., age, gender, and smoking history) were also documented.ResultsAmong the seven types of autoantibodies, only P53 and GBU4-5 were significantly increased in the LC group compared to the controls. Also, the P53 autoantibody was markedly different among the various subtype groups. Meanwhile, the GBU4-5 level was significantly higher in the small cell lung cancer (SCLC) patients compared to patients with adenocarcinoma (ADC). Autoantibodies against PGP9.5, SOX2, GBU4-5, and CAGE were found to be associated with stages. Their expressions were notably higher in the advanced stage (IV) versus early stages (I–II). Using logistic regression, the outcomes of LC prediction and stage prediction showed that the area under curve (AUCs) of the receiver operating characteristic (ROC) curves were 0.743 and 0.798, respectively.ConclusionsIn summary, our study confirmed the diagnostic value of tumor-associated autoantibodies, which may be useful as latent tumor markers to facilitate the detection of early LC. Single autoantibody testing is not yet sufficient in LC cancer screening, and the combined detection of autoantibodies can improve the sensitivity of detection compared with single antibody detection, especially for P53, PGP9.5, SOX2, GBU4-5, and CAGE autoantibodies.

P53 Antibodies as a Diagnostic Marker for Cancer: A Meta-Analysis.

Importance: The protein p53 is an unequivocal tumor suppressor that is altered in half of all cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: This systemic review and meta-analysis focuses on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed from the first study dated 1993 until May 2021 (date of submission of the manuscript). Study Selection: Studies were included that met the following criteria: (1) participants with cancer; (2) outcome results expressed in relation to the presence of a p53 antibody; (3) a primary outcome (disease-free survival, overall survival or progression-free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: (1) insufficient data available to evaluate outcomes; (2) animal studies; (3) studies with less than 10 participants. As a result, 12 studies were included in the analysis. Data Extraction and Synthesis: PRISMA guidelines were used for abstracting and assessing data quality and validity by three independent observers. The summary estimates were generated using a fixed-effect model (Mantel–Haenszel method) or a random-effect model (DerSimonian–Laird method), depending on the absence or presence of heterogeneity (I2). Main Outcome(s) and Measure(s): The primary study outcome was to determine the prognostic value of p53 Abs from a large population of patients with solid tumors, as determined before data collection. Results: In total, 12 clinical studies involving 2094 patients were included in the meta-analysis, and it was determined that p53 Abs expression in the serum significantly correlated with poorer survival outcomes of cancer patients (95% CI 1.48 [1.24, 1.77]; p < 0.00001). Conclusions and Relevance: This is the first meta-analysis proving the diagnostic utility of p53-Abs for cancer patients in predicting poorer outcomes. The serum-p53 value (s-p53-value) may be useful for future theranostics.

Presence of serum RalA and serum p53 autoantibodies in 1833 patients with various types of cancers.

RalA is a member of the Ras superfamily of small GTPases. The Anti-RalA autoantibodies (s-RalA-Abs) act as tumor markers in various types of cancer and are negatively associated with the p53 autoantibodies (s-p53-Abs). This study aimed to evaluate the relationship between s-RalA-Abs and s-p53-Abs in various types of cancer. A total of 1833 cancer patients (esophageal cancer, 172; hepatocellular carcinoma, 91; lung cancer, 269; gastric cancer, 317; colon cancer, 262; breast cancer, 364; and prostate cancer, 358) and 73 healthy subjects were enrolled in the study. The levels of s-RalA-Abs and s-p53-Abs were analyzed using enzyme-linked immunosorbent assay, and the positivity rates and relations between the two autoantibodies were evaluated. The cutoff values for s-RalA abs and s-p53 abs were set as mean + 2 standard deviation and the values higher than the cutoff values were defined as positive. The titers in all cancer types were significantly higher than those in the controls (P < 0.01). The positivity rates for s-RalA-Abs ranged between 11.7 and 21.5%, and those for s-p53-Abs ranged between 12 and 28.5%. A combined assay of the two antibodies revealed positivity rates of 20.9 and 44.2%. In Stage 0/I/II tumors, the positivity rates of the combination of the two antibodies ranged between 21.5 and 42.3%. The two autoantibodies were complementary to each other in the prostate and breast cancers, but independent in other carcinomas. The combined use of s-RalA-Abs and s-p53-Abs tended to increase the positivity rate in all cancers, including Stage 0/I/II cancers.

Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium.

Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer. Auto-antibodies to p53 were measured in prediagnostic blood samples of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.09-1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27; 95% CI, 1.62-3.19), but not thereafter (OR, 0.97; 95% CI, 0.76-1.24). In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw. Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk; however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer.

Serum p53 antibody: useful for detecting gastric cancer but not for predicting prognosis after surgery.

To establish the clinicopathological importance of serum p53 autoantibody (s-p53-Ab) titrations in patients with gastric cancer. Preoperative s-p53-Ab titers were analyzed in 448 gastric cancer patients between 2010 and 2017. Seropositive patients were divided into three groups based on their antibody titers: 1.31-10.0 U/mL (low group); 10.1-100 U/mL (medium group); and > 100 U/mL (high group). We evaluated the associations between the s-p53-Abs and clinicopathological factors, carcinoembryonic antigen (CEA) levels, and cancer antigen 19-9 (CA19-9) levels. Overall survival was analyzed by multivariate analyses. A total of 72 patients (16%) were positive for s-p53-Abs. The rate of positivity for s-p53-Abs + CEA + CA19-9 was significantly higher than that for CEA + CA19-9, even in stage I gastric cancers. Gender, tumor depth, lymphatic node metastases, and distant metastases were all significantly associated with the presence of s-p53-Abs; however, overall survival was not associated with the antibodies. The patients in the high titer group (> 100 U/mL) had a relatively worse survival than those in the other groups. Based on our findings, s-p53-Abs improve the overall rate of positivity for detecting gastric cancer, but the prognostic value of a high s-p53-Ab titer for predicting overall survival is limited.

Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a United States Prospective Cohort Consortium

Abstract Auto-antibodies to tumor suppressor p53 are found in a subset of colorectal cancer (CRC) patients. A prospective cohort study in the US (Cancer Prevention Study II) has recently reported a statistically significant 1.8-fold increased odds for the development of CRC based on pre-diagnostic sero-positivity for p53; the magnitude of this association decreased with longer time-span between blood sampling and diagnosis. In the present study, we sought to examine this association in a large US CRC cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early CRC detection biomarker. Methods: Antibody responses to p53 were measured in pre-diagnostic blood samples of 3,702 incident CRC cases (median [range] follow-up: 7.3 years [0–40 years]) and an equal number of controls, matched by age, race, and sex, from 9 US prospective cohorts. The association of sero-positivity to p53 with CRC risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. Results: Overall, 5% of controls and 7% of cases were sero-positive to p53, resulting in a statistically significant 33% increased CRC risk (OR: 1.33; 95% CI: 1.09, 1.61). The association was strongest for CRC diagnoses within 2 years after blood draw (OR: 2.73; 95% CI: 1.67, 4.45), with 15% sero-positive cases compared to 6% sero-positive controls. The number of sero-positive cases decreased with longer follow-up time (2–&amp;lt;5 years: 9%; 5–&amp;lt;10 years: 6%; ≥10 years: 3%) down to a proportion similar to that in controls resulting in the absence of an association of p53 sero-positivity with CRC risk after more than 5 years between blood draw and CRC diagnosis. Conclusion: In this large consortium of prospective cohorts, we found that pre-diagnostic sero-positivity to the tumor suppressor p53 was statistically significantly associated with a 2.7-fold increased risk of a subsequent CRC diagnosis within 2 years after blood draw, replicating the findings of the one previous cohort study examining this association. The findings suggest that while p53 sero-positivity may not be a useful predictor of long-term CRC risk, p53 auto-antibodies might be considered as part of a marker panel for early detection of this cancer.

P53 molecular approach to diagnosis and treatment of esophageal squamous cell carcinoma.

We reviewed our research concerning p53 molecules in esophageal squamous cell carcinoma by focusing on the p53 molecular diagnosis and treatment of esophageal squamous cell carcinoma. First, we developed diagnostic tools to analyze serum p53 autoantibodies to detect esophageal squamous cell carcinoma. Positive rate was around 25% to 30% in all patients and around 20% even in stage I patients. Presence of serum p53 antibodies was significantly associated with overexpression of p53 protein in tumor cells. Seropositive patients were more likely than seronegative patients to be resistant to chemotherapy. Monitoring of the titer of serum p53 autoantibodies was useful in predicting patients at high risk of recurrence and/or treatment response. Second, using Ad5CMV‐p53 for 10 patients with advanced esophageal squamous cell carcinoma, we carried out a phase I/II study of adenoviral‐mediated p53 gene therapy. Although no complete response was observed, local tumor was stabilized in nine patients. No serious adverse events related to Ad5CMV‐p53 were observed in these patients. One patient survived for over 5 years after the start of p53 gene therapy. Intratumoral injection of Ad5CMV‐p53 is therefore safe, feasible, and biologically active when given in multiple doses to patients with esophageal squamous cell carcinoma. Our observations from these clinical studies indicate that p53 is a useful molecular target both in the diagnosis and in the treatment of esophageal squamous cell carcinoma.

Multi-panel assay of serum autoantibodies in colorectal cancer.

Although serum p53 autoantibodies (s-p53-Abs) are induced even in the early stages of colorectal cancer, their positive rate is only approximately 20%. Therefore, we assessed the possibility of using other serum autoantibodies to increase the positive rates for detecting colorectal cancer. Autoantibodies against 17 tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, NY-ESO-1, p90, Sui1, HSP40, CyclinB1, HCC-22-5, c-myc, PrxVI, VEGF, HCA25a, p62, and Annexin II) were evaluated in 279 patients with colorectal cancer and 74 healthy controls. Cutoff values were fixed at mean + 3 standard deviations of serum titers in healthy controls. Autoantibodies with the highest positive rates were p53 (20%), RalA (14%), HSP70 (12%), and Galectin1 (11%). Combination assays using multiple autoantibodies increased the positive rates based on the number of autoantibodies used. Positive rates of 56, 62, 66, 71, and 73% were obtained with 6, 9, 11, 14, and 17 antibodies, respectively, for the overall disease. Moreover, these autoantibodies showed relatively high positive rates even during stage 0/I disease (55 and 70% with 6 and 17 antibodies, respectively). The measurement of set of 17 autoantibodies allowed autoantibody profiling in patients with colorectal cancer. The combination assay of six tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, and NY-ESO-1) achieved a positive rate of 56%. Such high positive rates will be helpful for detecting colorectal cancer regardless of tumor stages.

Prediagnostic Antibodies to Serum p53 and Subsequent Colorectal Cancer.

Background: The presence of circulating antibodies to the p53 tumor suppressor protein is a potential early detection colorectal cancer biomarker. However, studies of prediagnostic measures of p53 seropositivity in relation to colorectal cancer risk are limited.Methods: We conducted a nested case-control study of serum p53 autoantibodies and risk of colorectal cancer within the Cancer Prevention Study-II Nutrition Cohort. Among cohort participants who were cancer free at the time of blood collection, 392 were subsequently diagnosed with colorectal cancer over 11 years of follow-up. Two controls were matched to each case on birth date, blood draw date, race, and sex. Autoantibodies to p53 were detected in 41 of the 392 cases (10.5%) and 49 of the 774 controls (6.3%).Results: Participants who were seropositive for p53 antibodies before diagnosis were more likely to be subsequently diagnosed with colorectal cancer [RR = 1.77; 95% confidence interval (CI), 1.12-2.78]. This association was strongest within 3 years of diagnosis (RR = 2.26; 95% CI, 1.06-4.83). An association was also suggested when colorectal cancer was diagnosed 4 to <6 years after p53 measurement (RR = 1.84; 95% CI, 0.89-3.79), but not 6 or more years later (RR = 1.15; 95% CI, 0.44-2.99).Conclusions: If these results are confirmed, serum p53 antibodies may be useful on a panel of early detection markers for colorectal cancer.Impact: Individuals who were seropositive for p53 antibodies were twice as likely to develop colorectal cancer within the next 3 years compared with those who were seronegative. This marker is a good candidate for inclusion on an early detection marker panel for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(2); 219-23. ©2017 AACR.

Anti-p53 autoantibody as early diagnostic and prognostic marker of bronchogenic carcinoma in smokers

Background Mutations in the tumor protein 53 (TP53) gene can lead to expression of mutant p53 proteins that accumulate in cancer cells and can induce circulating p53 antibodies in patients with cancer. Neoplastic transformation leads to elevated plasma sialic acid concentration through shedding or secreting of sialic acid from tumor cell surfaces. Our work aims to evaluate the presence and prognostic role of these antibodies and sialic acid in patients with lung cancer.Patients and methods A total of 30 patients with lung cancer (five patients were presented with stage I, 10 patients with stage II, 10 patients with stage III, and five patients with stage IV) and 60 with nonmalignant disorders (30 smokers and 30 apparently healthy individuals) were evaluated for p53 antibodies by enzyme-linked immunosorbent assay and sialic acid by colorimetric methods.Results Anti-p53 antibodies and sialic acids levels in patients with bronchogenic carcinoma were significantly higher than smokers, and both levels were significantly higher than healthy controls (P<0.001). There was no statistically significant difference between stages III and IV of bronchogenic carcinoma of serum anti-p53 antibodies and sialic acid, but there was a statistically significant difference between stages I, II, and III, where the levels in stage III of bronchogenic carcinoma were significantly higher than stage II, and both levels were significantly higher than in stage I. There was a positive correlation between serum levels of anti P53 autoantibodies and the smoking index of the same patients. There was a positive correlation between serum levels of sialic acid and anti-p53 antibodies in the same patients with bronchogenic carcinoma.Conclusion Anti-p53 antibodies and sialic acid can be considered as sensitive for the biochemical changes associated with smoking and lung cancer. They may be used as markers for early diagnosis of lung cancer, and presence of them in smokers with primary lung cancer correlates with the severity and bad prognostic outcome of the disease.

Gold-Loaded Nanoporous Ferric Oxide Nanocubes with Peroxidase-Mimicking Activity for Electrocatalytic and Colorimetric Detection of Autoantibody.

The enzyme-mimicking activity of iron oxide based nanostructures has provided a significant advantage in developing advanced molecular sensors for biomedical and environmental applications. Herein, we introduce the horseradish peroxidase (HRP)-like activity of gold-loaded nanoporous ferric oxide nanocubes (Au-NPFe2O3NC) for the development of a molecular sensor with enhanced electrocatalytic and colorimetric (naked eye) detection of autoantibodies. The results showed that Au-NPFe2O3NC exhibits enhanced peroxidase-like activity toward the catalytic oxidation of 3,3',5,5'-tertamethylbenzidine (TMB) in the presence of H2O2 at room temperature (25 °C) and follows the typical Michaelis-Menten kinetics. The autoantibody sensor based on this intrinsic property of Au-NPFe2O3NC resulted in excellent detection sensitivity [limit of detection (LOD) = 0.08 U/mL] and reproducibility [percent relative standard deviation (% RSD) = <5% for n = 3] for analyzing p53-specific autoantibodies using electrochemical and colorimetric (naked eye) readouts. The clinical applicability of the sensor has been tested in detecting p53-specific autoantibody in plasma obtained from patients with epithelial ovarian cancer high-grade serous subtype (EOCHGS, number of samples = 2) and controls (benign, number of samples = 2). As Au-NPFe2O3NC possess high peroxidase-like activity for the oxidation of TMB in the presence of H2O2 [TMB is a common chromogenic substrate for HRP in enzyme-linked immunosorbent assays (ELISAs)], we envisage that our assay could find a wide range of application in developing ELISA-based sensing approaches in the fields of medicine (i.e., detection of other biomarkers the same as p53 autoantibody), biotechnology, and environmental sciences.

Serum KIF5A, KIF18A, and p53 Autoantibody Concentrations as Potential Biomarkers of Asbestos Exposure

Background: Asbestos-related diseases remain a significant occupational health problem in much of the world. Evidence of asbestos exposure is not always apparent in routine clinical evaluations of potentially exposed individuals, particularly in the initial stages of pathogenesis, so convenient biomarkers of exposure could be useful in the early identification of individuals at risk. Methods and findings: Based on prior research, we examined serum levels of kinesin family proteins (KIF5A and KIF18A) and p53 autoantibodies in 198 asbestosexposed workers and 164 unexposed controls. Exposed individuals were significantly more likely to have increased KIF5A and decreased KIF18A compared to the unexposed controls; p53 autoantibodies and exposure were unrelated. Conclusion: Serum kinesins may be useful biomarkers of asbestos exposure.