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Screen Of Molecular Makers Related To Progression And Metastasis Of Early Esophageal Squamous Cell Carcinoma

Posted on:2011-10-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:J LuFull Text:PDF
GTID:1114360305467846Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Background:Esophageal squamous cell carcinoma (ESCC), especially in northern China, is one of the common fatal cancers. ESCC is an aggressive cancer with poor prognosis. Most patients present with advanced stage disease when they were diagnosed, so they lost the best time for therapy. Early detection and therapay remains the best way for a cure. With the improvement of tumor therapy, the recommended therapy of early ESCC is endoscopic mucosal resection (EMR). The key point for EMR is to estimate the condition of infiltration of lesions and metastasis exactly, and the metastasis condition of lymph node directly determines the treatment modes. However, there are no effective examinations to evaluate the progression and metastasis of tumors. The most important reason for different tumors with different biological behaviours is that each tumor has its characteristic genetic alterations. Unfortunately there are no specific makers of the genetic alterations for progression and metastasis of tumors, so it would significantly be rational strategies to systemically analyze cancer tissues on molecular level and to find specific molecular markers for progression and metastasis. The aim of this study is to screen out ideal markers for predicting progression and metastasis of early ESCC.Methods:The first part:surgically resected specimens from 24 patients with early ESCC(T1N0 stage), were studied. According to the survival time, they were divided into two groups. Patients in death group were 11 cases who died in 40 months and patients in survival group were 13 cases with at least 80 months duration. The genomic DNA isolated from tumor tissues were hybridized to Agilent CGH microarray. The second part:16 of 24 were analyzed for expression of microRNAs by TaqMan Human MicroRNA Arrays.16 cases were divided into two groups based on the same standard.Results:1. Many chromosome alterations were identified in our study, including gains of 1q,3q,5p,6p,7q/p,8q/p,9q, 11q,12p,14q,16p,17q/p,18p, 19q/p,20q/p,22q and deletions of 3p,4q/p,5q,6p,9p,11q,13q,14q,18q,19q,21q. Compared with death group, some copy number changes occurred more frequent in survival group. They were gains of 1q,3q,5p,7q/p,8q/p,9q, 11q,12p,14q,16p, 17q,19q,20q,22q and loss of 4q/p,5q,13q. Some small scale changes occurred in the two groups were significantly different. They included gains of lq21.3-24, 3q21.1-24,3q26.1-26.33,5p13.1-15.31,7p22,7q11.23,8p11.2,8q22.1-24.3, 11q12.1-13.5,12p12.1-13.33,14q23.1,16p12.1-13.3,17q25.1,19q13.12, 20q11.21-13.33,22q12.1-13.2 and losses of 4p,4q31-35,5q22.3 and 13q12.21-12.2. Moreover,109 candidate genes for distinguishing the two groups were identified.2. Many microRNAs were found to be differently expressed between two groups in our study, and four microRNAs were identified for distinguishing these two groups. They include miR-574-3p, miR-19b, miR-31 and miR-28-3p.Conclusions:There are some specific changes of chromosome copy number, genes and microRNAs which might contribute to the potency for progression and metastasis of early ESCC.In our study, we screened out some specific markers of molecular genetics to predict the progression and metastasis of early ESCC. These markers included 109 genes with copy number changes and four microRNAs. The results of our study find the scientific proof for correct estimation on therapy of early ESCC.
Keywords/Search Tags:esophageal squamous cell carcinoma, progression, metastasis, array-CGH, microRNA
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