Prognostic value of C-reactive protein/albumin ratio in predicting overall survival of Chinese cervical cancer patients overall survival: comparison among various inflammation based factors.

Background: Many studies have shown the prognostic value of inflammation based factors in different cancers. This work aimed to explore the prognostic value of pretreatment C-reactive protein/albumin (CRP/Alb) ratio in patients with cervical cancer, and compared to other inflammatory prognostic factors, such as neutrophil/lymphocyte ratio(NLR), Glasgow prognostic score (mGPS), prognostic index (PI), platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), clinicopathological parameter and squamous cell carcinoma antigen (SCC-Ag). Methods: This study was a retrospective analysis of the data related to 229 patients with newly diagnosed cervical cancer. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. The correlation between CRP/Alb ratio and other prognostic factors were analyzed by Chi-Square or Fisher's exact test. Results: Multivariate analyses showed that CRP/Alb ratio was an independent predictor of overall survival (OS) in cervical squamous cell carcinoma (SCC) (HR, hazard ratio = 2.529; p = 0.045), but not in all cases of cervical cancer. However, NLR was a prognostic factor in the whole cervical cancer (HR = 2.47; p = 0.020) as well as in SCC subgroup (HR = 2.28; p = 0.038). Spearman's rank correlation analysis revealed that NLR showed a positive correlation with CRP/Alb ratio (p < 0.001). The combined index of NLR and CRP/Alb ratio could enhance the prognostic value compared to NLR or CRP/Alb ratio alone. Moreover, a high CRP/Alb ratio > 0.022 was associated with older patients (p < 0.001) and more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p < 0.001). In addition, NLR and CRP/Alb ratio were associated with SCC-Ag concentration in SCC. Furthermore, CRP/Alb ratio was a superior prognosis factor than mGPS, PI, PLR and PNI in SCC. Moreover, positive correlation was present among SCC-Ag, NLR and CRP/Alb ratio. Conclusions: CRP/Alb ratio might be considered as a novel prognosis factor and combined with NLR could improve the accuracy of OS prediction in patients with cervical cancer as well as its most common histological SCC subtypes.

Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract.

Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.

Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer.

Fusobacterium nucleatum (F. nucleatum, Fn) is associated with the colorectal cancer (CRC). Fn-infection could induce significant levels of serum Fn-specific antibodies in human and mice. The objective of this study was to identify Fn-infection that elicit a humoral response in patients with CRC and evaluate the diagnostic performance of serum anti-Fn antibodies. In this work, we showed the mean absorbance value of anti-Fn-IgA and -IgG in the CRC group were significantly higher than those in the benign colon disease group and healthy control group (P < 0.001). The sensitivity and specificity of ELISA for the detection of anti-Fn-IgA were 36.43% and 92.71% based on the optimal cut-off. The combination of anti-Fn-IgA and carcino-embryonic antigen (CEA) was better for diagnosing CRC (Sen: 53.10%, Spe: 96.41%; AUC = 0.848). Furthermore, combining anti-Fn-IgA with CEA and carbohydrate antigen 19-9 (CA19-9) (Sen: 40.00%, Spe: 94.22%; AUC = 0.743) had the better ability to classify CRC patients with stages I-II. These results suggested that Fn-infection elicited high level of serum anti-Fn antibodies in CRC patients, and serum anti-Fn-IgA level may be a potential diagnosing biomarker for CRC. Serum anti-Fn-IgA in combination with CEA and CA19-9 increases the sensitivity of detecting early CRC.

Antibodies Against Epstein-Barr Virus Glycoprotein gp42 for the Diagnosis of Nasopharyngeal Carcinoma.

BACKGROUND: Assessment of immunoglobulin A (IgA) antibody responses to Epstein-Barr virus (EBV) antigen is important for the early diagnosis of nasopharyngeal carcinoma (NPC). EBV glycoprotein gp42 has been shown to play an essential role in membrane fusion with B cells. The aim of the present study was to assess whether the antibodies to EBV glycoprotein gp42 in serum could be a novel marker for diagnosis of NPC. METHODS: EBV glycoprotein gp42 expressed in the recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to gp42 in serum. The blood samples were obtained from 406 participants (n = 208 patients with NPC and 198 healthy controls). Receiver operating characteristics (ROC) was used to calculate diagnostic accuracy. RESULTS: The ROC curves showed that IgA-gp42 ELISA had a sensitivity of 76.4%, specificity of 78.3% and an area under the curve (AUC) of 0.856 (95% CI, 0.82 - 0.891) to diagnose NPC. Furthermore, gp42 maintained diag- nostic capacity in NPC patients who were IgA-viral capsid antigen (VCA) negative (87.5%, 64.1% and 0.844 [95% CI, 0.776 - 0.912]). Combining gp42 and VCA improved the diagnostic capacity compared with the individual tests (89.9%, 94.4% and 0.973 [95% CI, 0.959 - 0.9871). CONCLUSIONS: The EBV glycoprotein complex gp42 acts as a novel biomarker for diagnosis of NPC and improves identification of patients with VCA-negative NPC.

Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma.

To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort (n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort (n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls (p < 0.001). In the training cohort, the IgA-gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC.

Study of support vector machine and serum surface-enhanced Raman spectroscopy for noninvasive esophageal cancer detection.

The ability of combining serum surface-enhanced Raman spectroscopy (SERS) with support vector machine (SVM) for improving classification esophageal cancer patients from normal volunteers is investigated. Two groups of serum SERS spectra based on silver nanoparticles (AgNPs) are obtained: one group from patients with pathologically confirmed esophageal cancer (n=30) and the other group from healthy volunteers (n=31). Principal components analysis (PCA), conventional SVM (C-SVM) and conventional SVM combination with PCA (PCA-SVM) methods are implemented to classify the same spectral dataset. Results show that a diagnostic accuracy of 77.0% is acquired for PCA technique, while diagnostic accuracies of 83.6% and 85.2% are obtained for C-SVM and PCA-SVM methods based on radial basis functions (RBF) models. The results prove that RBF SVM models are superior to PCA algorithm in classification serum SERS spectra. The study demonstrates that serum SERS in combination with SVM technique has great potential to provide an effective and accurate diagnostic schema for noninvasive detection of esophageal cancer.

[The protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion injury and coagulopathy after excision of liver cancer].

OBJECTIVE: To observe the protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion (I/R) injury and coagulopathy in liver cancer patients undergoing excision of hepatic cancer after occlusion of hepatic blood flow. METHODS: A prospective randomly controlled study was conducted. Sixty patients with liver cancer classified as Child-Pugh class A undergoing hepatectomy in the Department of Hepatobiliary Surgery of Sun Yat-sen University Cancer Center from October 2011 to March 2013 were enrolled. The patients were randomized into control group and Xuebijing group (each patient received 100 mL Xuebijing injection added to 0.9% saline as a preoperative treatment for 3 days). Complete blood count, coagulation function, hepatic function, serum pro-inflammatory cytokines and alpha-fetoprotein (AFP) levels were determined before and after operation. RESULTS: Forty-five out of 60 patients were enrolled eventually, with 23 patients in control group and 22 in Xuebijing group, and among them 43 patients were positive for hepatitis B surface antigen (HBsAg) at admission. Compared with those before operation, the postoperative levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) in control and Xuebijing groups were significantly elevated, prothrombin time (PT) and activated partial prothrombin time (AfYIT) were significantly prolonged, and white blood cells (WBC) , proportion of neutrophils (N) and C-reactive protein (CRP) were significantly increased (P<0.05 or P<0.01 ). Although the above indexes in Xuebijing group after operation were lower than those in control group in different degrees [ALT (U/L): 213.1 (80.4-796.6) vs. 265.8 (15.6-882.3), AST (UIL): 194.1 (65.4-914.2) vs. 264.3 (15.4-475.9), LDH (lg,U/L): 5.69 ± 0.72 vs. 5.71 ± 0.72, PT (s): 15.24 ± 2.16 vs. 14.41 ± 1.33, AfYIT (s): 31.51 ± 7.04 vs. 29.47 ± 4.90, WBC (x 109/L) : 13.4 7 ± 4.66 vs. 14.58 ± 4.40, N: 0.87 ± 0.06 vs. 0.87 ± 0.04, CRP (mg/L): 40.64 (16.93-189.59) vs. 45.64 ( 1.65-349.40) J, no statistical significance was found between the groups (all P>0.05 ). The preoperative levels of tumor necrosis factor-a (TNF -a) and interleukin-6 OL-6) were both less than 1.0 ng/L, and the postoperative levels of TNF-a showed no significant change, and IL-6 was increased to 485.10 (104.00-837.50) ng/L and 193.26 (95.10-385.20) ng/L in control and Xuebijing groups respectively (P<0.01). The serum high mobility group box-1 ( HMGB1 ) protein levels after operation were higher than those of preoperative in both groups (both P<0.01), but the postoperative HMGB1 in Xuebijing group were significantly lower than those in control group (j.Lg/L: 268.73 ± 5.56 vs. 277.12 ± 2.92, P<0.01). Acute physiology and chronic health evaluation ll (APACHE ll) score in Xuebijing group was significantly lower than that in control group (4.18 ± 3.75 vs. 4.53 ± 2.34, t=5.328, P=0.027), and the first passage of flatus and defecation after operation in Xuebijing group were significantly earlier than those in control group [exhaust time (days): 3 (2-4) vs. 3 (2-4), U=-2.023, P=0.043; defecation time (days): 4 (2-6) vs. 5 (3-8), U =-2.926, P=0.003 J. However, no difference was found between two groups in the postoperative and total hospital days. Spearman rank correlation analysis showed there were positive correlations between hepatitis B virus (HBV)-DNA levels and preoperative ALT (r=0.414, P=0.044) and AST (r=0.405, P=0.024) in 33 HBV-DNA positive patients, but there was no significant correlation between HBV -DNA levels or other preoperative liver function indicators. CONCLUSIONS: Hepatic I/R injury and coagulopathy may occur in liver cancer patients undergoing resection of cancer with occlusion of hepatic blood flow. Xuebijing injection may inhibit the release of serum pro-inflammatory cytokines, thereby alleviate hepatic I/R injury and promote the recovery of intestinal function. But it does not offer protective effect on coagulopathy.