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Study On The Expression Of Mir-93,Mir-106b And Potential Targets Of Wnt/β-cateninin Laryngeal Squamous Cell Carcinoma

Posted on:2013-07-02Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2234330371977720Subject:Department of Otolaryngology Head and Neck Surgery
Abstract/Summary:PDF Full Text Request
【Objective】Laryngeal squamous cell carcinoma is one of the most common malignant tumors.In recent years, MicroRNA was developed as early cancer detection of molecular markers, thecancer early diagnosis, cancerous tumors, disease prediction, and became a new hotspot. But thestudyof the expression profiles in laryngeal squamous cell carcinoma ((LSCC)) were onlystaying in testing their expression.To pick up high expression of mir-106b, mir-93 in laryngealsquamous cell carcinoma and adjacent normal tissue with gene chip, test with q-PCR in theparaffin samples. At the same time, the important protein expression of MUC1, beta catenin,cyclinD1 in the WNT/beta catenin pathway, combined with pathological material and themolecular mechanism, were discussed and became molecular target therapy in laryngealsquamous cell carcinoma.【Methods】1. The expression of mir-106b, mir-93 of paraffin samples in LSCC was determined bylooped-primer Real-time PCR and combined with pathological material analysis.2. Predicted microRNA corresponding Target genes with professional database, such as SangermicroRNA (miRBase), Target Scan, online software (http://cloud.genomics.org.cn/home.xhtml)and choosed the high score as prediction to support the site.3. Mucin1,β-catenin,cyclinD1 expression were examined in paraffin-embedded tissue thatcomprised 65 LSCC and 35 adjacent normal larynx control specimens with MaxVisionimmunohistochemistry staining. The difference from positive expression of three indicators andclinical parameters were estimated using Chi- Square, Spearman Rank Correlation method.【Results】1. Higher expression of mir-93 and mir-106b in LSCC was comprised with normal tissues ofadjacent to carcinoma. The difference is statistically significant (p = 0.017, p = 0.019).2.Target genes were forecast to mir-93, mir-106b, mainly including MUC1、β-catenin、cyclinD1. 3. Mir-106b, mir-93 and the clinical stages was inversely related (r = 0.467, r = 0.380). Thelevels of mir-106b and mir-93 increased markedly in laryngeal carcinoma with stageⅢincomparison to stageⅠ,ⅡandⅣ(p = 0.000, p = 0.002). Both of them and lymph nodes werestatistically significant. Mir-106b, mir-93 was positively associated with lymph node metastasis(r = 0.300, r = 0.442). Both of them and the lymph node metastasis were statistically significant(p = 0.015, p = 0.000).4. Higher Mucin1 expression in LSCC was 44.6 %that comprised with normal tissues ofadjacent to carcinoma 8.6 %.The ectopic expression ofβ-catenin in cytoplasm and nucleus was58.5%, normal tissues adjacent to carcinoma was 2.9% that had significant differences (p<0.001).Higher cyclinD1 expression in LSCC was 78.5 % that comprised with normal tissues of adjacentto carcinoma had significant differences (p<0.001).The results showed that Mucin1 andβ-catenin expression were positively correlated (r=0.361,p=0.013) ,β-catenin and cyclinD1expression were positively correlated (r=0.210,p=0.003)5. With chi-square test, MUC1 in lymph node metastasis positive expression rate of positiverate was 21.1%, without lymph node metastasis positive rate was 54.3% that had significantdifferences (P = 0.014). The ectopic expression ofβ-catenin was 30.0%, 72.7% and 50.0% inpathologic stage low, medium and high differentiation. All of them were statistically significantdifferences (P = 0.024).The results with each other showed that the low differentiationcomprised with medium differentiation were statistically significant difference (P = 0.034). Theectopic expression ofβ-catenin was 36.8% in the lymph node metastasis comprised to withoutlymph node metastasis and had a statistically significant difference (P = 0.023). HigherCyclinD1 expression in LSCC was 70.0%, 90.9% and 63.6% in pathologic stage low, mediumand high differentiation. All of them were statistically significant differences (P = 0.035).CyclinD1 positive expression rate in the lymph node metastasis was 57.9%, without lymph nodemetastasis was 87.0% that had statistically significant difference (P = 0.024). The positiveexpression of MUC1 and cyclinD1, the ectopic expression ofβ-catenin were no statisticalsignificance about age, the clinical stages and tumor site.【Conclusions】1. The microRNAs related laryngeal squamous cell carcinoma with lymphatic metastasis aredetermined and studied on function and clinical parameters related research, for providing newmethods.2. Higher Mucin1 expression in LSCC of the cytoplasm and the ectopic expression ofβ-catenin, higher cyclinD1 expression, as new biological markers, have a synergistic effect on laryngealsquamous cell carcinoma.
Keywords/Search Tags:microRNA, Laryngeal tumor, squamous cell carcinoma, Mucin1, β-catenin, cyclinD1, q-PCR, Immunohistochemistry
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