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The Analysis Of Biological Prognostic Factors Of Esophageal Squamous Cell Carcinoma

Posted on:2017-08-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:J LiFull Text:PDF
GTID:1314330482494385Subject:Oncology
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Background:Esophageal cancer is a highly invasive tumor with a poor prognosis. Inflammatory cells are found to be related with cancer prognosis in many malignancies. However the prognostic values of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) in esophageal squamous cell carcinoma (ESCC) are contentious.Methods:we performed a retrospective study of 178 patients undergone radical resection and a complete peripheral blood count was performed on all patients 1 week before surgery. Kaplan-Meier curves with log-rank tests were adopted for overall survival (OS) and disease-free survival (DFS) analysis. Univariate and multivariate analysis using a Cox regression model were performed with known clinical and demographic prognostic factors to evaluate prognostic parameters using the enter method.Results:Of the 178 patients,39 (21.9%) were women and 139 (78.1%) were men. The median age was 56 years (range 38-76 years); The median follow-up was 39 months (range 3-88 months). Multivariate analysis using a Cox regression model showed that LMR were not significantly associated with OS (HR= 0.733,95% CI:0.397-1.353,.P=0.321) and DFS (HR= 0.850,95% CI:0.491-1.473, P=0.562). NLR or PLR were also not significantly correlated with OS or DFS.Conclusions:NLR, PLR and LMR could not serve as prognostic biomarkers for patients with operable ESCC.Background:Esophageal cancer is a highly invasive tumor with a poor prognosis. Lymphocytes play an important role in systemic immune responses, but their role in cancers varies depending on the specific tumor microenvironment.The aim of this study was to provide evidence for tumor-infiltrating lymphocytes as a prognostic biomarker in esophageal squamous cell carcinoma (ESCC).Methods:Tumor-infiltrating lymphocytes analysis was retrospectively performed on full-face hematoxylin and eosin stained sections from 127 patients. Kaplan-Meier curves with log-rank tests were adopted for overall survival (OS) and disease-free survival (DFS) analyses. Univariate and multivariate analyses of Cox regression model were performed with known histopathologic and demographic prognostic factors to evaluate the prognostic parameters with the enter method, and for TILs scores as continuous variables.Results:A majority (92.6%) of tumors had at least 10% stromal tumor-infiltrating lymphocytes (range,10% to 90%), and 84.3% of cancers had at least 10% intraepithelial tumor-infiltrating lymphocytes(range,10% to 40%). Multivariate analysis showed progressively better overall survival (P< 0.001, HR= 0.968,95% CI 0.955-0.981) and disease-free survival (P= 0.005, HR= 0.982,95% CI 0.970-0.995) in patients with higher stromal tumor-infiltrating lymphocytes.Conclusions:Increasing stromal lymphocytic infiltration is an independent prognostic factor for esophageal squamous cell carcinoma treated by radical resection.Background:The p14ARF/MDM2/p53 pathway is known to play an important role in tumor progression by cell cycle control, although the association between this pathway and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in the p14ARF/MDM2/p53 pathway and prognosis in ESCC patients with radical resection.Methods:124 ESCC patients with radical resection were included in this retrospective study and genotyped using the MassArray method. Kaplan-Meier curves with log-rank tests were adopted for overall survival (OS) and disease-free survival (DFS) analysis. Univariate and multivariate analysis using a Cox regression model were performed with known clinical and demographic prognostic factors to evaluate prognostic parameters using the enter method.Results:According to multivariate Cox hazard analysis and multiple testing, the TC/CC genotype of p14ARF rs3814960 was shown to be strongly related to a decreased overall survival (OS) (HR=2.765,95% CI:1.330-5.750, P=0.006, Pc=0.030) and disease-free survival (DFS) (HR= 2.449,95% CI:1.301-4.608, P=0.005, Pc= 0.025). Moreover, patients with the A/- +AA genotype of MDM2 rs34886328 had a notably increased OS (HR = 0.272,95% CI:0.131-0.564, P=4.7×10-4, Pc=0.003) and DFS (HR= 0.217,95% CI: 0.109-0.429, P=1.1×10-5, Pc= 6.6×10-5). We also found that these two single nucleotide polymorphisms (SNPs) had a cumulative effect on the prognosis of ESCC, with the OS (P< 0.001) and DFS (P< 0.001) being shortest for patients carrying both of these unfavorable genotypes.Conclusions:Two SNPs in the p14ARF/MDM2/p53 pathway, p14ARF rs3814960 and MDM2 rs34886328, were found to be significantly associated with the OS and DFS of ESCC, and may thus serve as predictors of ESCC, if these results are further validated in a larger population.Background:Esophageal cancer is the eighth most common malignancy and squamous cell carcinoma accounts for more than 90% of esophageal cancer in China. The clinical variables of esophageal squamous cell carcinoma (ESCC) currently used to predict outcomes are imprecise. HPV plays an important role in the development of cervical cancer and is an independent prognostic factor of oropharyngeal cancer, anal cancer and cervical cancer. This study aimed to explore the associations between HPV infection in tumor tissues and the prognosis of ESCC.Methods:we performed a retrospective study of 135 patients undergone radical resection andDNA was extracted from paraffinsections of ESCC tissues.14 HPV subtypes(HPV16, 18,31,33,35,39,45,51,52,56,58,59,66,68) from DNA samples were detected by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and PCR.SPSS 16.0 software was used for statistical analysis.Results:Of the 135 patients,26 (19.3%) were women and 109 (80.7%) were men. The median age was 58 years (range 40-78 years).We found thatonly 1 patient infected with HPV 16 by MALDI-TOF MSin the tumor tissue, accounting for 0.74% of the total patients. The remaining 13 HPV subtypes were not found in the ESCC tissues. Consistent withMALDI-TOF MS method, the results of PCR showed only 1 patientinfected with HPV.Conclusions:The study found that patients with esophageal squamous cell carcinoma tissue in the lower HPV infection could not serve as an independent prognostic biomarker in ESCC in Central China because of the low infection rates. In addition, HPV may not be an importantrisk factors of ESCC in Central China and the roles of HPV may not be same in different regions.
Keywords/Search Tags:esophageal squamous cell carcinoma, lymphocyte-monocyte ratio, neutrophil-lymphocyte ratio, platelets-lymphocyte ratio, prognostic biomarker, tumor-infiltrating lymphocytes, prognostic factor, overall survival, disease-free survival, p14ARF, MDM2, p53
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