本文選題：RCC + 免疫組織化學�。� 參考：《第四軍醫(yī)大學》2014年碩士論文

【摘要】：腎細胞癌（renal cell carcinoma，RCC）是腎臟惡性腫瘤的最常見類型。RCC對放療和化療均不敏感，早期RCC通過手術治療常能取得良好的治療效果。但是對于進展期和晚期RCC，手術治療則效果欠佳。近年來，雖然已有多種阻斷腫瘤細胞生長或血管生成的抗腫瘤藥物用于晚期RCC的治療，但其治療效果仍不夠理想，晚期RCC患者的5年生存率仍很低。 隨著對腫瘤分子機制研究的不斷深入，已有多條信號通路被證實參與了RCC的發(fā)生和發(fā)展過程。這些信號通路在正常腎臟細胞的惡性轉化，腫瘤細胞的增殖、侵襲和轉移等多種生物學過程中發(fā)揮著重要的調控作用。因此，對RCC發(fā)生發(fā)展的分子機制的研究以及針對這些信號通路的分子靶向治療藥物的研發(fā)對于晚期RCC的治療具有重要的意義。 Notch信號通路對于胚胎發(fā)育、組織自我更新、細胞干性維持、細胞增殖和凋亡等過程均有重要的調節(jié)作用。近年來，越來越多的研究證明Notch信號通路參與了多種腫瘤生物學行為的調節(jié)，，包括腫瘤細胞的增殖、分化、凋亡及基因組穩(wěn)定性等。眾多研究表明Notch1在多種腫瘤中具有促進腫瘤或抑制腫瘤的效應。目前，已有多個關于Notch1及Notch信號通路與RCC的研究，但是，人們對于RCC中Notch1的作用觀點并不一致，仍需進一步探討和明確。 為了明確Notch信號通路在RCC中的作用，我們應用免疫組織化學染色和Western-blot檢測了RCC臨床標本中Notch1的表達,并對其與其他臨床病理特征的相關性進行了分析。我們還應用Western-blot和RT-qPCR的方法檢測了Notch1和Hes1在腎細胞癌786-O細胞和腎小管上皮細胞HK-2細胞中的表達。免疫組織化學染色結果顯示Notch1在RCC腫瘤組織中的陽性表達率明顯低于正常腎組織，其陽性率分別為23.2%和73.2%。RT-qPCR的結果顯示RCC腫瘤組織中Notch1及其下游分子Hes1的mRNA水平較正常腎組織低。統(tǒng)計分析發(fā)現(xiàn)，晚期(AJCC III+IV)RCC中Notch1的表達顯著低于早期(AJCC I+II)RCC，并且Fuhrman III的RCC中Notch1的表達也低于Fuhrman I+II級RCC中的水平。細胞檢測結果顯示，786-O細胞中Notch1和Hes1的mRNA水平均明顯低于HK-2細胞。基于以上實驗結果，我們認為Notch1和Notch信號通路可能參與RCC的發(fā)生和發(fā)展，Notch1的低表達和Hes1的低轉錄水平可能提示RCC的惡性程度較高，Notch1的表達水平和Notch信號通路的活化程度可作為RCC預后判斷的一項指標。
[Abstract]:Renal cell carcinoma (RCC) is the most common type of renal malignancy. RCCs are not sensitive to radiotherapy and chemotherapy. But for advanced and advanced RCCs, surgical treatment is not effective. In recent years, although many antitumor drugs have been used to block tumor cell growth or angiogenesis in the treatment of advanced RCC, the therapeutic effect is still not satisfactory. The 5-year survival rate of advanced RCC patients is still very low. With the further study of tumor molecular mechanism, several signal pathways have been proved to be involved in the occurrence and development of RCC. These signaling pathways play an important role in many biological processes, such as malignant transformation of normal renal cells, proliferation, invasion and metastasis of tumor cells. Therefore, the study of the molecular mechanism of RCC development and the development of molecular targeted therapy drugs for these signaling pathways are of great significance for the treatment of advanced RCC. The Notch signaling pathway is of great significance for embryonic development and tissue self-renewal. Cell dryness maintenance, cell proliferation and apoptosis all play an important role in regulating the process. In recent years, more and more studies have demonstrated that Notch signaling pathway plays an important role in the regulation of tumor biological behavior, including proliferation, differentiation, apoptosis and genomic stability of tumor cells. Numerous studies have shown that Notch1 has the effect of promoting tumor or inhibiting tumor in many kinds of tumors. At present, there have been many studies on Notch1 and Notch signaling pathway and RCC. However, people do not agree on the role of Notch1 in RCC, so we need to further explore and clarify the role of Notch signaling pathway in RCC. The expression of Notch1 in RCC was detected by immunohistochemistry and Western-blot, and the correlation between Notch1 and other clinicopathological features was analyzed. Western-blot and RT-qPCR were used to detect the expression of Notch1 and Hes1 in 786-O and HK-2 cells of renal cell carcinoma. The expression of Notch1 in RCC tissues was significantly lower than that in normal renal tissues. The positive rates of Notch1 and its downstream molecule Hes1 in RCC tumor tissues were 23.2% and 73.2%, respectively. RT-qPCR showed that the mRNA levels of Notch1 and its downstream molecule Hes1 in RCC were lower than those in normal renal tissues. Statistical analysis showed that the expression of Notch1 in late stage AJCC III IVCC was significantly lower than that in early stage AJCC I IIR CCS, and the expression of Notch1 in Fuhrman III RCC was lower than that in Fuhrman I II RCC. The results showed that the mRNA levels of Notch1 and Hes1 in Hes1 cells were significantly lower than those in HK-2 cells. Based on the above experimental results, We believe that Notch1 and Notch signaling pathway may be involved in the occurrence and development of RCC. The low expression of Notch1 and the low transcription level of Hes1 may suggest that the expression of Notch1 and the activation of Notch signaling pathway may be the prognosis of RCC. A measure of judgment.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R737.11

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