[Show abstract][Hide abstract] ABSTRACT: Heat shock factor 1 (HSF1) is a powerful, multifaceted modifier of carcinogenesis. However, the clinical significance and biologic function of HSF1 in esophageal squamous cell carcinoma (ESCC) remain unknown.
HSF1 was detected in ESCC cell lines, fibroblast cell lines and ESCC xenograft tumors and human ESCC tissues by real-time RT-PCR and western blotting. HSF1 protein expression was analyzed by immunochemistry in 134 ESCC patients followed by correlation with clinicopathological parameters.
HSF1 expression is weak in fibroblast cell 3T3 and moderate in ESCC cell Eca109, but increasing expression of HSF1 was observed in both of 3T3 and Eca109 cells when they interplayed with each other. In Eca109 xenograft tumors, both tumor cells and stromal fibroblasts showed stronger expression of HSF1. In ESCC patients, the HSF1 expression in tumor or in stromal cells was significantly associated with tumor stage, lymph node metastasis and clinical stage. Multivariate analysis demonstrated a significant negative correlation between disease-free survival (DFS), overall survival (OS) and the HSF1 expression in stromal cells (P < 0.05) but not in tumor cells. Additionally, the expression of HSF1 in tumor cells or stromal cells was an independent factor for DFS (P = 0.032 or P = 0.012) and OS (P = 0.017 or P = 0.013) in metastatic ESCC patients but not for locoregional ESCC. ESCC patients with low HSF1 in both tumor cells and stromal cells had the longest survivals (P < 0.001).
The interaction of tumor cells and stromal fibroblasts increases the expression of HSF1 reciprocally in tumor microenvironment. The HSF1 expression in stromal cells was significantly associated with poor prognosis of ESCC.
Preview · Article · Dec 2015 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: Objectives
This study was designed to establish an ELISA method, as well as the cut-off value, for IgA against Epstein–Barr virus (EBV) viral capsid antigen (VCA), as a screening assay for nasopharyngeal carcinoma (NPC) in southern China. In addition, the correlation between relative optical density (rOD) values from ELISA and titers from the immunoenzymatic assay (IEA) was also evaluated.
Two hundred and fifty-eight NPC cases, 33 non-NPC head and neck cancer patients, and 1156 healthy controls were recruited for this study. VCA-IgA and early antigen (EA)-IgA were measured by ELISA kits and IEA in parallel.
The total precision of the VCA-IgA ELISA achieved a level of <13.0% coefficient of variation. An rOD value of 1.60 for the VCA-IgA ELISA was determined as the cut-off point for southern China, and the sensitivity and specificity for NPC diagnosis when using this cut-off value were 93.0% and 92.4%, respectively. The area under the receiver operating characteristic curve (ROC-AUC) value was 0.969. The correlation coefficient between titers and rOD values was 0.957. rOD values were correlated with NPC overall stage and lymph node involvement.
The cut-off level established in our study could be used to facilitate more accurate diagnosis of NPC in southern China. The rOD value might be an index for NPC prognosis, since it shows a good correlation with the titer from IEA.
Full-text · Article · Aug 2014 · International Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Although the alterations of lipid profile in lung cancer have been documented, the prognostic value of serum HDL-C level and its correlation with inflammation in NSCLC remain unknown.
Levels of preoperative serum lipid concentrations (including HDL-C, LDL-C, TC, and TG) and the inflammatory biomarker C-reactive protein level (CRP) were retrospectively analyzed in 228 patients with NSCLC and in 300 healthy controls. The serum lipid levels in these two populations were compared. Univariate and multivariate cox hazards analyses were performed to investigate the prognostic value of serum lipid levels in NSCLC. The correlation between CRP and lipid profile were also analyzed.
Compared with those in normal controls, the serum HDL-C, LDL-C, and TC levels were statistically decreased and the TG levels were significantly increased in 228 NSCLC patients. The patients with decreased levels of HDL-C had significantly lower 5-year survival rates than those with normal HDL-C, not only in the whole NSCLC cohort but also in the subgroups stratified according to the disease T, N classifications, and metastasis, whereas the other lipid components were not independent prognostic factors for NSCLC. Of the lipid components, a lower HDL-C level was observed more often in patients with a high CRP level than in those with a normal CRP level. Spearman's rank correlation analysis revealed that the HDL-C level presented a negative correlation with the CRP level (r = -0.360, p<0.001).
A decreased level of preoperative HDL-C was found to be associated with poor survival in patients with NSCLC. Serum HDL-C level may be a clinical prognosis factor for NSCLC patients. In addition, a negative correlation was present between the levels of HDL-C and CRP, the well-known inflammation biomarker.
[Show abstract][Hide abstract] ABSTRACT: The widespread reverse syphilis screening algorithm involves 1 more treponemal test than the traditional screening algorithm, resulting in increased medical costs. In the first screening step of the algorithm, a chemiluminescence microparticle immunoassay is used to detect Treponema pallidum (TP) antibody on the basis of signal-to-cutoff (S/CO) ratios. We hypothesized that by analyzing S/CO ratios, we could determine a strategy to reduce unnecessary confirmatory testing.
The ARCHITECT Syphilis TP assay using the chemiluminescence microparticle immunoassay was used as a syphilis screening test, and all reactive results were followed up with a toluidine red unheated serum test (TRUST) and a TP particle agglutination (TPPA) assay. We evaluated the S/CO ratios of 319 reactive samples of a total of 8980 that were included in the screening tests. A receiver operating characteristic curve was used to determine the optimal S/CO ratio to predict confirmatory TPPA results.
When the S/CO ratio was 9.9 or greater, the specificity and positive predictive value were both determined to be 100.0%. All samples (194/194) with S/CO ratios of 9.9 or greater, even with negative results for TRUST, were confirmed to be positive for treponemal antibody.
A sample with an S/CO ratio of 9.9 or greater in initial screening does not need an extra confirmatory TPPA test, although the sample has a negative result for TRUST. We propose a potentially cost-effective reverse screening algorithm, obviating the need for the secondary treponemal testing in 65.2% of the screening-reactive samples.
No preview · Article · Jan 2014 · Sexually transmitted diseases
[Show abstract][Hide abstract] ABSTRACT: Various studies have been searching for new tumor biomarkers for breast cancer for years. However, so far, few markers have been proved clinically useful except CA153. Based on knowledge that most adenocarcinomas including breast carcinoma expressed Cytokeratin19, the authors studied CK19-2G2,a novel fragment of cytokeratin19 shedding into serum in breast cancer patients.
The serum samples of four hundred and seventeen patients including three hundred and three (fifty-four DCIS and two hundred and forty-nine stage I-III) PBC patients and one hundred and fourteen MBC patients, eighty-one healthy controls and twenty-one breast benign disease patients were provided for measurement of CK19-2G2, CEA and CA153.The correlation between clinicopathological characters, prognosis and CK19-2G2 levels was further studied.
The serum CK19-2G2 levels in breast cancer patients were significantly higher than that in healthy and benign controls. For breast cancer patients, CK19-2G2 levels in MBC were significantly higher than that in PBC patients. The sensitivities of CK19-2G2 for breast carcinoma are as high as CEA and CA153, and up to 71% in MBC patients. Serum CK19-2G2 levels (≥2 mU/mL) were associated with pathological stages, tumor size (≥2 cm), lymph node involvement, and HER2 status. Multivariate analysis revealed that high serum CK19-2G2 level was an independent factor for relapse (0.029) and death (0.040) in breast cancer patients.
Serum CK19-2G2 may be an independent indicator for prognosis and a candidate marker for monitoring metastasis in breast cancer.
[Show abstract][Hide abstract] ABSTRACT: Our aim was to investigate whether adding ω-3 polyunsaturated fatty acids (PUFAs) to parenteral nutrition (PN) could reduce inflammation and improve immune function in patients following esophageal cancer surgery. In this pilot study, 60 patients with esophageal cancer were divided into 2 groups (30 patients in each group). All patients had total scores of more than or equal to 3 on the nutritional risk screening (NRS2002) test recommended by the European Society of Parenteral Enteral Nutrition, which showed that all patients had nutritional risk and should receive nutritional support. Both groups received isocaloric and isonitrogenous PN. One group received a ω-3 PUFAs supplement. Key indicators of inflammation [serum procalcitonin (PCT) level and the ratio of CD4(+) to CD8(+) (CD4(+)/CD8(+) ratio)] were determined intraoperatively and 24, 72, and 144 h postoperatively. PCT level was notably lower and CD4(+)/CD8(+) ratio was markedly higher in the ω-3 PUFAs group (P = 0.007 for PCT level and P = 0.012 for CD4(+)/CD8(+) ratio) on postoperative day 6 but not on postoperative days 1 and 3. ω-3 PUFAs supplemented PN can reduce inflammation and improve immune function in patients following esophageal cancer surgery. A larger trial is required to see whether ω-3 PUFAs supplementation of PN improves the clinical outcomes of patients following esophageal cancer surgery.
No preview · Article · Feb 2013 · Nutrition and Cancer
[Show abstract][Hide abstract] ABSTRACT: A two-stage study was conducted in southern China to determine and validate an optimal combination of Epstein-Barr virus (EBV)-related seromarkers for nasopharyngeal carcinoma (NPC) screening. In the first stage, six seromarkers [VCA-IgA, EA-IgA, Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), EBNA1-IgG, Zta-IgA and Rta-IgG] were detected by enzyme-linked immunosorbent assay (ELISA) and two traditional NPC screening seromarkers (VCA-IgA and EA-IgA) were detected by immunofluorescence assay (IFA) in serum samples from 191 NPC patients and 337 controls. An optimal combination of seromarkers for NPC diagnosis was selected using logistic regression models. Results showed that the diagnostic performances of VCA-IgA and EA-IgA tested by ELISA were superior to the performances of the same seromarkers by IFA. VCA-IgA combined with EBNA1-IgA by ELISA was identified as the optimal combination, with an area under the receiver operating characteristic (ROC) curve (AUC) up to 0.97, a sensitivity of 95.3% and a specificity of 94.1% for classification of NPCs vs. controls. In the second stage, 5,481 participants aged 30-59 years and without clinical evidence of NPC were recruited into a population-based NPC screening program from May 2008 to February 2009 in Sihui City, China. Their sera were tested simultaneously by both the new and the traditional screening schemes and eight early stage NPC patients were subsequently histopathologically confirmed. The traditional and the new screening schemes had comparable specificity (estimated as 98.5%), but the sensitivity of the new scheme (75.0%) was significantly higher than that of the traditional one (25.0%). The combination of VCA-IgA and EBNA1-IgA by ELISA outperforms the traditional NPC screening scheme and could become the preferred serodiagnostic strategy for NPC screening in high-incidence areas.
No preview · Article · Jul 2012 · International Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: High serum human epidermal growth factors receptor-2 (HER2) extracellular domain (ECD) has been identified as an independent prognostic indicator of poor prognosis in metastatic breast cancer. However, its prognostic value in primary operable breast cancer was still controversial. We aim to investigate the correlation between serum HER2 ECD levels and tissue HER2 status, the association between serum HER2 ECD levels and clinicopathological characteristics, and their impacts on disease-free survival (DFS) and overall survival (OS) in primary operable breast cancer.
Two hundred and fifty-two primary operable breast cancer patients pretreated from 2002 to 2009 in Sun Yat-Sen University Cancer Center were enrolled in this study. Serum HER2 ECD was measured by chemiluminescent assay, and tissue HER2 status was accessed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) assay.
There was a significant correlation between serum HER2 ECD levels and HER2 tissue status (P < 0.001, R = 0.36). High serum HER2 ECD levels (≥15 ng/mL) were significantly associated with age (≥35 years) (P = 0.028), postmenopausal status (P < 0.001), stage III (P < 0.001), tumor size (≥2 cm) (P < 0.001), lymph node involvement (P < 0.001), negative estrogen receptor (P = 0.005), and progesterone receptor status (P = 0.001). Multivariate analysis showed that high serum HER2 ECD level was an independent prognostic factor of worse DFS (P = 0.014) and OS (P = 0.014) in primary operable breast cancer patients.
Serum HER2 ECD level can reflect tissue HER2 status and can be an independent prognostic indicator for primary operable breast cancer patients.
No preview · Article · Nov 2011 · Journal of Cancer Research and Clinical Oncology