本文選題：DSCR1基因 + 喉咽鱗狀細(xì)胞癌�。� 參考：《山東大學(xué)》2012年博士論文

【摘要】：目的通過研究喉咽鱗狀細(xì)胞癌組織與癌旁組織中DSCR1基因蛋白的表達(dá),了解其表達(dá)與腫瘤臨床特征的關(guān)系,探討DSCR1基因?qū)ο卵树[狀細(xì)胞癌的生物學(xué)行為的影響,為以DSCR1基因為靶點的抗腫瘤治療提供生物學(xué)依據(jù)。 方法收集94例喉咽鱗狀細(xì)胞癌病例,有78例同時取癌旁組織,通過免疫組織化學(xué)p-V9000法,使用兔抗DSCR1抗體DCT3,檢測DSCR1基因蛋白在喉咽鱗狀細(xì)胞癌與正常癌旁組織中的表達(dá),數(shù)據(jù)輸入SAS8.2軟件進(jìn)行統(tǒng)計學(xué)分析,采用卡方檢驗比較不同性別、年齡、組織學(xué)分級、臨床分期、部位、生長方式、淋巴結(jié)轉(zhuǎn)移以及吸煙史組間表達(dá)差異,配對t檢驗方法對78例同一病人的腫瘤與癌旁組織中基因蛋白的表達(dá)差異進(jìn)行分析,P0.05為有統(tǒng)計學(xué)意義。 結(jié)果腫瘤組織中DSCR1基因蛋白表達(dá)陽性率94.9%,癌旁組織中表達(dá)陽性率35.9%,有極顯著統(tǒng)計學(xué)意義(t值23.69,P0.001)；DSCR1基因的表達(dá)與組織學(xué)分級、TNM分期顯著相關(guān)(P0.05)；DSCR1基因的表達(dá)與與腫瘤的發(fā)病年齡、性別、部位、生長方式、淋巴結(jié)轉(zhuǎn)移以及吸煙史均無關(guān)(P0.05)。 結(jié)論 1.在喉咽癌腫瘤組織與癌旁組織中,DSCR1基因蛋白的表達(dá)存在明顯的差異。 2.DSCR1基因與腫瘤的組織學(xué)分級有顯著關(guān)系,分化程度越差,DSCR1基因蛋白的表達(dá)陽性率越高,與TNM分期及淋巴結(jié)轉(zhuǎn)移的關(guān)系有待于進(jìn)一步研究。 3.在喉咽癌的形成及發(fā)展進(jìn)程中,DSCR1基因必定發(fā)揮了重要的作用,可能是此基因的失活或功能失調(diào)導(dǎo)致了腫瘤的發(fā)展不受控制,并影響了腫瘤的生物學(xué)特征,是一個很有前途的腫瘤基因治療靶點。 目的通過檢測喉咽癌組織與癌旁組織中微血管密度數(shù)值,研究血管因素與腫瘤侵襲性間的相關(guān)性。并與前期測定的DSCR1基因表達(dá)之間做相關(guān)性分析,討論DSCR1基因與喉咽癌血管生成之間的關(guān)系,探討DSCR1基因?qū)硌拾┑陌l(fā)生、血管新生等生物學(xué)行為特性的影響。 方法使用免疫組化PV9000方法,在與第一部分相同的94例喉咽鱗狀細(xì)胞癌病例,通過CD34抗體染色標(biāo)記血管內(nèi)皮細(xì)胞,計算微血管密度(MVD)值,通過與臨床資料進(jìn)行統(tǒng)計學(xué)分析,探討MVD與各種臨床病理參數(shù)之間的關(guān)系,并通過前期測定的腫瘤組織中DCT3抗體標(biāo)記的DSCR1基因表達(dá)與MVD之間做相關(guān)性分析,MVD結(jié)果以均數(shù)±標(biāo)準(zhǔn)差表示,兩組間比較采用t檢驗(方差齊),三組以上樣本間關(guān)系采用單因素方差分析,P0.05表示差異有顯著性。MVD與DSCR1表達(dá)相關(guān)性檢驗用Spearman相關(guān)分析。 結(jié)果在喉咽癌組織中MVD平均為17.57±10.61條/400倍視野,癌周正常組織為12.61±7.67條/400倍視野,經(jīng)統(tǒng)計學(xué)分析差異顯著(P0.05)。MVD與腫瘤頸淋巴結(jié)轉(zhuǎn)移的關(guān)系研究發(fā)現(xiàn),轉(zhuǎn)移組中MVD平均為18.96±11.63條/400倍視野,而非轉(zhuǎn)移組為16.17±9.61條/400倍視野,經(jīng)統(tǒng)計學(xué)分析差異顯著(P0.05)；MVD與喉咽癌的病理分級的關(guān)系發(fā)現(xiàn),高分化組的MVD平均為16.29±9.98條/400倍視野,中分化組為18.58±10.35條/400倍視野,低分化組為20.48±13.61條/400倍視野,三組比較差異顯著(P0.05)。對瘤內(nèi)血管密度MVD與腫瘤臨床分期的相關(guān)性研究表明,TNM分期Ⅰ～Ⅱ組MVD平均為16.13±9.61/400倍視野,而Ⅲ～Ⅳ組為18.43±11.61條/400倍視野,經(jīng)統(tǒng)計學(xué)分析差異顯著(P0.05)；本實驗表明MVD與患者的發(fā)病年齡、性別、腫瘤生長部位、生長方式及吸煙史等均無明顯相關(guān)性(P0.05)；在喉咽癌腫瘤組織中隨著MVD的升高,DSCR1基因的表達(dá)也逐漸增強(qiáng),結(jié)果具有顯著的統(tǒng)計學(xué)意義(P0.0001),且兩者之間為正相關(guān)的關(guān)系(r=0.698)。 結(jié)論 1.喉咽癌組織中MVD與腫瘤的組織學(xué)分級、TNM分期、淋巴結(jié)轉(zhuǎn)移有關(guān)。說明腫瘤不同的生物學(xué)特征伴隨不同的微血管密度表達(dá),可以通過檢測MVD判斷喉咽癌的預(yù)后,以及高M(jìn)VD的喉咽癌患者行預(yù)防性頸淋巴結(jié)清掃及術(shù)后的放、化療等綜合治療是必要的。 2.在喉咽癌鱗狀細(xì)胞癌,隨著DSCR1基因的表達(dá)活性增加,腫瘤微血管密度的也增強(qiáng),兩者存在正相關(guān)的關(guān)系,證實了DSCR1基因與腫瘤血管生成的密切相關(guān)性,說明DSCR1基因可以影響喉咽癌的侵襲、轉(zhuǎn)移等過程,是很有前途的腫瘤治療靶點。 目的了解VEGF-C mRNA及DSCRl mRNA在喉咽鱗癌組織及癌旁組織中的表達(dá)水平,進(jìn)一步驗證VEGF及DSCRl基因與腫瘤的關(guān)系,并將VEGF-C mRNA表達(dá)水平與DSCR1mRNA水平做相關(guān)性分析,探討DSCR1基因與喉咽癌血管生成之間的關(guān)系。 方法通過RT-PCR方法檢測DSCR1mRNA及VEGF-C mRNA在43例喉咽鱗癌組織及21例癌旁組織中的表達(dá)情況,在不同組織學(xué)分級、臨床分期、淋巴結(jié)轉(zhuǎn)移之間進(jìn)行比較,并對二者的表達(dá)進(jìn)行相關(guān)性分析。 結(jié)果43例喉咽癌中35例可檢測到DSCRl mRNA陽性,占81.39%,21例正常癌旁組織中8例可檢測DSCR1mRNA陽性,占38.10%,喉咽鱗狀細(xì)胞癌DSCR1mRNA表達(dá)的平均相對光密度值為0.91±0.10,明顯高于正常癌旁組織0.61±0.08,差異具有統(tǒng)計學(xué)意義(P0.05)；DSCR1mRNA的表達(dá)在不同的組織學(xué)分級、及淋巴結(jié)轉(zhuǎn)移均有顯著差異(P0.05)。43例喉咽癌32例可檢測到VEGF-C mRNA,占74.42%,21例正常組織中6例可檢測至VEGF-C mRNA,占28.57%,癌周組織平均相對灰度值為(0.56±0.19),癌內(nèi)組織平均相對灰度值為(1.21±0.41),二組之間比較差異均有統(tǒng)計學(xué)意義(P0.05)。43例腫瘤組織中DSCR1mRNA表達(dá)與VEGF-C mRNA表達(dá)的相關(guān)性,經(jīng)Spearman相關(guān)性分析,兩者之間成正相關(guān)。 結(jié)論 1.在喉咽癌腫瘤組織與癌旁組織中,DSCR1mRNA的表達(dá)存在明顯的差異。DSCR1與不同的腫瘤組織學(xué)分級及淋巴結(jié)轉(zhuǎn)移有顯著關(guān)系,此基因與腫瘤的生物學(xué)行為密切相關(guān)。 2. VEGF-C mRNA的表達(dá)從癌周組織到癌內(nèi)組織相對灰度值呈增高趨勢,有顯著差異,說明VEGF-C與癌癥的發(fā)生發(fā)展有密切關(guān)系。 3.在喉咽癌腫瘤組織中DSCR1mRNA表達(dá)與VEGF-CmRNA表達(dá)呈正相關(guān),DSCR1基因與喉咽鱗狀細(xì)胞癌的血管生成存在密切關(guān)系。
[Abstract]:Objective to study the expression of DSCR1 gene protein in the tissues of larynx squamous cell carcinoma and paracancerous tissue, to understand the relationship between the expression of the tumor and the clinical features of the tumor, and to explore the effect of the DSCR1 gene on the biological behavior of the hypopharyngeal squamous cell carcinoma, and to provide a biological basis for the anti tumor treatment of the target based on the DSCR1 base.
Methods 94 cases of hypopharynx squamous cell carcinoma were collected and 78 cases were collected simultaneously. The expression of DSCR1 gene protein in hypopharynx squamous cell carcinoma and normal para cancerous tissue was detected by immunohistochemistry p-V9000 method and Rabbit anti DSCR1 antibody DCT3. The data were analyzed by SAS8.2 software, and the same sex was compared with the chi square test. No, age, histological grade, clinical stage, location, growth mode, lymph node metastasis and smoking history, the difference in the expression of gene protein in 78 cases of the same patient's tumor and para cancerous tissue was analyzed by paired t test, and P0.05 was statistically significant.
Results the positive rate of DSCR1 gene protein expression in tumor tissues was 94.9%, the positive rate of the Para Para tissue was 35.9%, with significant statistical significance (t value 23.69, P0.001); the expression of DSCR1 gene was significantly correlated with the histological grade, TNM staging (P0.05); the expression of the DSCR1 gene and the age of the tumor, sex, location, growth mode, lymph node, and lymph node Metastasis and the history of smoking were not related (P0.05).
conclusion
1. there was a significant difference in the expression of DSCR1 protein in tumor tissues and adjacent tissues of hypopharyngeal carcinoma.
There is a significant relationship between the 2.DSCR1 gene and the histological grade of the tumor. The worse the degree of differentiation, the higher the expression of DSCR1 gene protein, the relationship with TNM staging and lymph node metastasis need to be further studied.
3. in the process of the formation and development of hypopharynx cancer, the DSCR1 gene is bound to play an important role. It may be that the inactivation or dysfunction of the gene may lead to the uncontrolled development of the tumor, and affect the biological characteristics of the tumor. It is a promising target for the treatment of tumor genes.
Objective to investigate the correlation between vascular factors and tumor invasiveness by detecting the microvascular density in the tissues of hypopharyngeal carcinoma and adjacent tissues, and to analyze the correlation between the DSCR1 gene expression and the relationship between the DSCR1 gene and the angiogenesis of the hypopharynx cancer, and explore the occurrence of the DSCR1 gene and the angiogenesis of the hypopharynx. The effects of biological behavior characteristics.
Methods using immunohistochemical PV9000 method, 94 cases of larynx squamous cell carcinoma the same as the first part were used to mark vascular endothelial cells by CD34 antibody staining, and the value of microvascular density (MVD) was calculated. The relationship between MVD and various clinicopathological parameters was analyzed by statistical analysis with clinical data. The correlation analysis between the DSCR1 gene expression of DCT3 antibody markers in the tissue and MVD was analyzed, and the results of MVD were expressed with mean standard deviation. The two groups were compared with t test (Fang Chaqi), and the relationship between the three groups was analyzed by single factor analysis of variance. P0.05 indicated that the difference was significant in the correlation test of.MVD and DSCR1 expression by Spearman correlation analysis.
Results the average MVD of MVD in the hypopharynx cancer tissue was 17.57 + 10.61 /400 times of vision, and the normal tissue of the carcinoma was 12.61 + 7.67 times of /400 fold. The statistical difference was significant (P0.05) and the relationship between the tumor neck lymph node metastasis and the MVD was 18.96 + 11.63 /400 times of vision in the transfer group, while the non metastasis group was 16.17 + 9.61 /400 times. The visual field was statistically significant (P0.05). The relationship between the MVD and the histopathological classification of hypopharynx found that the average MVD of the high differentiation group was 16.29 + 9.98 /400 times of vision, the middle differentiation group was 18.58 + 10.35 /400 times of vision, the low differentiation group was 20.48 + 13.61 /400 times of vision, and the three groups were significantly different (P0.05). The intra tumor vascular density MVD and swelling were found. The correlation study of the clinical staging of the tumor showed that the average MVD of TNM stage I to II group was 16.13 + 9.61/400 fold, while the group III to IV was 18.43 + 11.61 /400 times of /400, and the difference was significant (P0.05). The experiment showed that there was no significant correlation between MVD and the age of the patients, the sex, the tumor growth position, the growth mode and the smoking history. Sex (P0.05); the expression of DSCR1 gene was gradually increased with the increase of MVD in the tumor tissues of hypopharynx cancer, and the results had significant statistical significance (P0.0001), and the relationship between them was positively related (r=0.698).
conclusion
The histological grading, TNM staging and lymph node metastasis in 1. hypopharynx cancer tissues are related to the different biological characteristics of the tumor with different microvascular density expressions. The prognosis of the laryngynx cancer can be judged by the detection of MVD, as well as the comprehensive treatment of prophylactic neck lymph node dissection and postoperative radiotherapy and chemotherapy for high MVD hypopharynx cancer patients. It is necessary.
2. in the squamous cell carcinoma of hypopharynx cancer, with the increase of the expression of DSCR1 gene, the tumor microvessel density is also enhanced. There is a positive correlation between the two. It confirms the close correlation between the DSCR1 gene and the angiogenesis of tumor. It shows that the DSCR1 gene can affect the invasion and metastasis of the larynx cancer, and it is a promising target for cancer treatment.
Objective to investigate the expression of VEGF-C mRNA and DSCRl mRNA in hypopharynx squamous cell carcinoma tissue and para cancer tissue, to further verify the relationship between VEGF and DSCRl genes and tumor, and to analyze the correlation between the expression level of VEGF-C mRNA and the level of DSCR1mRNA, and to explore the relationship between the DSCR1 gene and the angiogenesis of the hypopharynx cancer.
Methods the expression of DSCR1mRNA and VEGF-C mRNA in 43 cases of hypopharynx squamous cell carcinoma and 21 para cancerous tissues were detected by RT-PCR method. The comparison of the histological grade, clinical stage and lymph node metastasis was carried out, and the expression of the two were analyzed.
Results in 43 cases of larynx cancer, 35 cases were detected to be DSCRl mRNA positive, accounting for 81.39%. 8 cases of normal para cancerous tissues in 21 cases were detected DSCR1mRNA positive, accounting for 38.10%. The average relative light density of DSCR1mRNA expression in hypopharynx squamous cell carcinoma was 0.91 + 0.10, which was significantly higher than that of normal para cancerous tissue (0.61 + 0.08), and the difference was statistically significant (P0.05); DSCR1mRNA There were significant differences in histological grade and lymph node metastasis (P0.05) in 32 cases of hypopharynx cancer in.43, VEGF-C mRNA was detected in 74.42%. In 21 normal tissues, 6 cases were detected to VEGF-C mRNA, 28.57%, and the average relative gray value of the tissue was (0.56 + 0.19), and the average relative gray value in the tissues was (1.21 + 0.41), and two groups were between the two groups. The difference was statistically significant (P0.05) the correlation between the expression of DSCR1mRNA and the expression of VEGF-C mRNA in the tumor tissues of.43, and the correlation between them was positively correlated with the Spearman correlation analysis.
conclusion
1. there is a significant difference in the expression of DSCR1mRNA in the tumor tissues and para cancerous tissues of the hypopharynx cancer..DSCR1 is closely related to the histological grade and lymph node metastasis of different tumors. This gene is closely related to the biological behavior of the tumor.
The expression of 2. VEGF-C mRNA increased from the peritacid tissue to the relative gray level in the tissues, which showed significant differences, indicating that VEGF-C was closely related to the development of cancer.
3. there was a positive correlation between the expression of DSCR1mRNA and the expression of VEGF-CmRNA in hypopharyngeal carcinoma tissues. DSCR1 gene is closely related to angiogenesis in hypopharyngeal squamous cell carcinoma.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R739.65

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