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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Down-regulation of C/EBP homologous protein (CHOP) expression in gastric cardia adenocarcinoma: Their relationship with clinicopathological parameters and prognostic significance.

OBJECTIVE: C/EBP homologous protein (CHOP) is a multi-functional protein involved in the apoptosis pathway of endoplasmic reticulum stress (ERS) and is related to cancer progression. The purpose of this study was to assess CHOP expression as a prognostic biomarker in gastric cardia adenocarcinoma (GCA). METHODS: The levels of CHOP mRNA and protein in GCA and matched adjacent non-cancerous tissues were evaluated by quantitative real-time-polymerase chain reaction (qRT-PCR) and western blot. Furthermore, the CHOP protein expression and localization were examined by immunohistochemistry in GCA and corresponding adjacent non-cancerous tissues, gastritis and normal cardiac tissues. The association of CHOP expression with clinical pathological parameters and prognosis of GCA patients was statistically analyzed. RESULTS: Compared with adjacent non-cancerous tissues, the CHOP was down-regulated at mRNA and protein levels in GCA (P<0.01). In addition, immunohistochemistry analysis showed that CHOP positivity was lower in GCA than that in paired adjacent non-cancerous tissues, gastritis and normal tissues (P<0.01). CHOP expression rate gradually decreased with an increase in clinical stage, tumor differentiation and lymph node metastasis of GCA (P<0.05). Kaplan-Meier survival analysis revealed that low expression of CHOP correlated with poor prognosis of GCA patients. Moreover, univariate and multivariate analyses showed that CHOP was an independent prognostic marker for overall survival of GCA patients. CONCLUSIONS: Our results suggest that low CHOP expression predicts poor prognosis of GCA patients, and CHOP may be potentially a prognostic biomarker for GCA.

Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice.

PURPOSE: We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (MMTV-erbB2) mice with estrogen receptor-positive tumors. METHODS: MMTV-erbB2 mice were randomly divided into three experimental groups with 20 mice in each group. MMTV-erbB2 mice were treated with daily subcutaneous injections of vehicle or rhG-CSF (low-rhG-CSF group, rhG-CSF 0.125 µg; vehicle-rhG-CSF group, normal saline 0.25 µg; and high-rhG-CSF group, rhG-CSF 0.25 µg) at 3 months of age. Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction. RESULTS: Low, but not high, rhG-CSF doses significantly accelerated mammary tumorigenesis in MMTV-erbB2 mice. Short-term treatment with rhG-CSF could significantly promote the development of preinvasive mammary lesions. The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%. CONCLUSION: We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo. Identification of G-CSF genes helped us further understand the mechanism by which G-CSF promotes cancer. Low doses of rhG-CSF could significantly increase tumor latency and increase tumor multiplicity and burden. Moreover, rhG-CSF effectively promotes development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.