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Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma.

ABSTRACT: The key-stone-pathogen, Porphyromonas gingivalis associates not only with periodontal diseases but with a variety of other chronic diseases such as cancer. We previously reported an association between the presence of Porphyromonas gingivalis in esophageal squamous cell carcinoma (ESCC) and its progression. We now report the diagnostic and prognostic potential of serum immunoglobulin G and A antibodies (IgG/A) against Porphyromonas gingivalis for ESCC.An enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of Porphyromonas gingivalis IgG and IgA in 96 cases with ESCC, 50 cases with esophagitis and 80 healthy controls.The median serum levels of IgG and IgA for P. gingivalis were significantly higher in ESCC patients than non-ESCC controls. P. gingivalis IgG and IgA in serum demonstrated sensitivities/specificities of 29.17%/96.90% and 52.10%/70.81%, respectively, and combination of IgG and IgA produced a sensitivity/specificity of 68.75%/68.46%. The diagnostic performance of serum P. gingivalis IgA for early ESCC was superior to that of IgG (54.54% vs. 20.45%). Furthermore, high serum levels of P. gingivalis IgG or IgA were associated with worse prognosis of ESCC patients, in particular for patients with stage 0-IIor negative lymphnode metastasis, and ESCC patients with high levels of both IgG and IgA had the worst prognosis. Multivariate analysis revealed that lymph node status, IgG and IgA were independent prognostic factors.The IgG and IgA for P. gingivalis are potential serum biomarkers for ESCC and combination of IgG and IgA improves the diagnostic and prognostic performance. Furthermore, serum P. gingivalis IgG and IgA can detect early stage ESCC.

SUBMITTER: Gao SG

PROVIDER: S-EPMC5753462 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma.

Gao She-Gan SG Yang Jun-Qiang JQ Ma Zhi-Kun ZK Yuan Xiang X Zhao Chen C Wang Guang-Chao GC Wei Hua H Feng Xiao-Shan XS Qi Yi-Jun YJ

BMC cancer 20180103 1

<h4>Background</h4>The key-stone-pathogen, Porphyromonas gingivalis associates not only with periodontal diseases but with a variety of other chronic diseases such as cancer. We previously reported an association between the presence of Porphyromonas gingivalis in esophageal squamous cell carcinoma (ESCC) and its progression. We now report the diagnostic and prognostic potential of serum immunoglobulin G and A antibodies (IgG/A) against Porphyromonas gingivalis for ESCC.<h4>Methods</h4>An enzyme ...[more]

PMID: 29298684

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Project description:BackgroundChaperones are ubiquitous conserved proteins critical in stabilization of new proteins, repair/removal of defective proteins and immunodominant antigens in innate and adaptive immunity. Periodontal disease is a chronic inflammatory infection associated with infection by Porphyromonas gingivalis that culminates in the destruction of the supporting structures of the teeth. We previously reported studies of serum antibodies reactive with the human chaperone Hsp90 in gingivitis, a reversible form of gingival disease confined to the oral soft tissues. In those studies, antibodies were at their highest levels in subjects with the best oral health. We hypothesized that antibodies to the HSP90 homologue of P. gingivalis (HtpG) might be associated with protection/resistance against destructive periodontitis.Methodology/principal findingsELISA assays using cloned HtpG and peptide antigens confirmed gingivitis subjects colonized with P. gingivalis had higher serum levels of anti-HtpG and, concomitantly, lower levels of attachment loss. Additionally, serum antibody levels to P. gingivalis HtpG protein were higher in healthy subjects compared to patients with either chronic or aggressive periodontitis. We found a negative association between tooth attachment loss and anti-P. gingivalis HtpG (p = 0.043) but not anti-Fusobacterium nucleatum (an oral opportunistic commensal) HtpG levels. Furthermore, response to periodontal therapy was more successful in subjects having higher levels of anti-P. gingivalis HtpG before treatment (p = 0.018). There was no similar relationship to anti-F. nucleatum HtpG levels. Similar results were obtained when these experiments were repeated with a synthetic peptide of a region of P. gingivalis HtpG.Conclusions/significanceOUR RESULTS SUGGEST: 1) anti-P. gingivalis HtpG antibodies are protective and therefore predict health periodontitis-susceptable patients; 2) may augment the host defence to periodontitis and 3) a unique peptide of P. gingivalis HtpG offers significant potential as an effective diagnostic target and vaccine candidate. These results are compatible with a novel immune control mechanism unrelated to direct binding of bacteria.

Project description:Purpose: The present study focused on exploring the associations of Porphyromonas gingivalis (P. gingivalis) infection and low Beclin1 expression with clinicopathological parameters and survival of esophageal squamous cell carcinoma (ESCC) patients, so as to illustrate its clinical significance and prognostic value. Methods: Immunohistochemistry (IHC) was used to detect P. gingivalis infection status and Beclin1 expression in 370 ESCC patients. The chi-square test was adopted to illustrate the relationship between categorical variables, and Cohen's kappa coefficient was used for correlation analysis. Kaplan-Meier survival curves with the log-rank test were used to analyse the correlation of P. gingivalis infection and low Beclin1 expression with survival time. The effects of P. gingivalis infection and Beclin1 downregulation on the proliferation, migration and antiapoptotic abilities of ESCC cells in vitro were detected by Cell Counting Kit-8, wound healing and flow cytometry assays. For P. gingivalis infection of ESCC cells, cell culture medium was replaced with antibiotic-free medium when the density of ESCC cells was 70-80%, cells were inoculated with P. gingivalis at a multiplicity of infection (MOI) of 10. Result: P. gingivalis infection was negatively correlated with Beclin1 expression in ESCC tissues, and P. gingivalis infection and low Beclin1 expression were associated with differentiation status, tumor invasion depth, lymph node metastasis, clinical stage and prognosis in ESCC patients. In vitro experiments confirmed that P. gingivalis infection and Beclin1 downregulation potentiate the proliferation, migration and antiapoptotic abilities of ESCC cells (KYSE150 and KYSE30). Our results provide evidence that P. gingivalis infection and low Beclin1 expression were associated with the development and progression of ESCC. Conclusion: Long-term smoking and alcohol consumption causes poor oral and esophageal microenvironments and ESCC patients with these features were more susceptible to P. gingivalis infection and persistent colonization, and exhibited lower Beclin1 expression, worse prognosis and more advanced clinicopathological features. Our findings indicate that effectively eliminating P. gingivalis colonization and restoring Beclin1 expression in ESCC patients may contribute to preventation and targeted treatment, and yield new insights into the aetiological research on ESCC.

Dataset Information

Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma.

Publications

Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma.

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