【摘要】：背景胃癌是全球最常見(jiàn)的消化道惡性腫瘤之一。亞洲日本、韓國(guó)及我國(guó)是胃癌高發(fā)區(qū),我國(guó)每年新發(fā)病例約40萬(wàn)例,占世界總發(fā)病例數(shù)的42%。早期胃癌患者術(shù)后5年生存率可達(dá)90%以上,但絕大多數(shù)胃癌在確診時(shí)屬進(jìn)展期,或已經(jīng)發(fā)生了腫瘤轉(zhuǎn)移,5年生存率不足30%。要減少胃癌的死亡率,最有效的措施就是早發(fā)現(xiàn)和早治療,分子生物學(xué)的發(fā)展為胃癌機(jī)制的研究提供了先進(jìn)的技術(shù)手段和方法學(xué),對(duì)胃癌治療方案的制定具有重要的指導(dǎo)意義。miRNA是一類長(zhǎng)約18~22個(gè)核苷酸的保守的非編碼小分子RNA,miRNA在轉(zhuǎn)錄或轉(zhuǎn)錄后水平負(fù)調(diào)控蛋白質(zhì)編碼基因的表達(dá):通過(guò)與其靶基因m RNA非完全互補(bǔ)或近似完全互補(bǔ)結(jié)合,導(dǎo)致m RNA降解或抑制其翻譯。從miRNA被發(fā)現(xiàn)以來(lái),許多研究報(bào)道了腫瘤組織中miRNA異常表達(dá),并證實(shí)了miRNA與一些抑癌因子和促癌因子有著顯著相關(guān)性。目的本研究通過(guò)檢測(cè)胃癌患者癌組織與癌旁組織差異表達(dá)的miRNA,探討其表達(dá)水平與腫瘤大小、TNM分期的相關(guān)性及與轉(zhuǎn)移狀態(tài)的相關(guān)性。采用生物信息學(xué)手段預(yù)測(cè)篩選出與胃癌侵襲和轉(zhuǎn)移相關(guān)性最大的靶基因,并探討其如何通過(guò)靶基因影響胃癌細(xì)胞的增殖和侵襲能力。方法(1)本研究選取3對(duì)胃癌和癌旁組織樣本進(jìn)行芯片檢測(cè),通過(guò)q RT-PCR方法對(duì)上一步篩選出的27個(gè)miRNA在胃癌組織及癌旁組織的表達(dá)水平進(jìn)行驗(yàn)證。(2)為了探索miRNA與胃癌發(fā)生發(fā)展的關(guān)系,對(duì)發(fā)生轉(zhuǎn)移和未發(fā)生轉(zhuǎn)移的胃癌樣本中的miR-223、miR-20a和miR-150這3種miRNA的表達(dá)情況以及患者的生存情況進(jìn)行分析統(tǒng)計(jì)。實(shí)時(shí)熒光定量PCR檢測(cè)84個(gè)已發(fā)生轉(zhuǎn)移胃癌樣品和48個(gè)未發(fā)生轉(zhuǎn)移胃癌樣品中miR-223、-20a和-150的的表達(dá)。(3)為了檢測(cè)miR-223對(duì)胃癌細(xì)胞增殖能力的影響,選用GT3TKB和MKN45作為研究對(duì)象。首先,測(cè)定了原始的GT3TKB和MKN45中miR-223的表達(dá)水平。接下來(lái)在GT3TKB和MKN45細(xì)胞系中分別轉(zhuǎn)染了化學(xué)合成的miR-223的擬似物(mimics)和抑制物RNA(inhibitor)。其次,對(duì)轉(zhuǎn)染后的細(xì)胞進(jìn)行Transwell小室侵襲實(shí)驗(yàn)及劃痕愈合實(shí)驗(yàn)。(4)為了尋找miRNA-223的靶基因,用生物信息學(xué)手段預(yù)測(cè)并根據(jù)經(jīng)驗(yàn)規(guī)則和已發(fā)表的研究成果篩選出與胃癌侵襲和轉(zhuǎn)移相關(guān)性最大的靶基因PAX6。在GT3TKB和MKN45細(xì)胞系中分別轉(zhuǎn)染了miR-223 mimics和miR-223 inhibitor,提取了轉(zhuǎn)染后GT3TKB和MKN45以及對(duì)應(yīng)的對(duì)照組細(xì)胞的總RNA,用RT-PCR方法檢測(cè)PAX6的表達(dá)水平,并用Western blot方法檢測(cè)PAX6的表達(dá)情況。進(jìn)一步用q RT-PCR方法及Western blot方法檢測(cè)132例臨床胃癌組織樣品中miR-223和PAX6表達(dá)水平,并進(jìn)行兩者相關(guān)性分析。結(jié)果(1)胃癌細(xì)胞中差異表達(dá)miRNA的篩選研究:結(jié)果顯示,13個(gè)miRNA在胃癌組織中的表達(dá)顯著上調(diào),14個(gè)miRNA在胃癌組織中表達(dá)呈下調(diào)。進(jìn)一步驗(yàn)證發(fā)現(xiàn),有21個(gè)miRNA與芯片實(shí)驗(yàn)結(jié)果相符。其中10個(gè)在胃癌組織中高表達(dá),11個(gè)在胃癌組織中低表達(dá)。6種miRNA的表達(dá)在胃癌與癌旁組織中的差異無(wú)統(tǒng)計(jì)學(xué)意義。其中,差異最顯著的3個(gè)miRNA分別為miR-223、miR-20a和miR-150。(2)異常表達(dá)的miRNA在發(fā)生轉(zhuǎn)移的胃癌組織中的表達(dá)情況及患者生存分析:結(jié)果顯示,miR-223表達(dá)量與腫瘤大小、TNM分期顯著相關(guān)(P0.05),其與轉(zhuǎn)移狀態(tài)的相關(guān)性極顯著(P0.01);miR-20a與TNM分期顯著相關(guān)(P0.05),與轉(zhuǎn)移狀態(tài)相關(guān)性極顯著(P0.01);miR-150僅與TNM分期相關(guān)性顯著(P0.05)。接著分析了76例具有嚴(yán)重的組織學(xué)性狀的胃癌樣品的miR-223表達(dá)水平,使用Kaplan-Meier生存分析對(duì)這些樣品的miR-223與生存率相關(guān)性進(jìn)行分析,結(jié)果顯示miR-223低表達(dá)組的無(wú)病生存率顯著高于miR-223高表達(dá)組。這些結(jié)果表明miR-223表達(dá)量與胃癌發(fā)展有關(guān)。(3)miR-223對(duì)胃癌細(xì)胞遷移和侵襲生物學(xué)行為作用的研究:通過(guò)實(shí)驗(yàn)發(fā)現(xiàn)高侵襲力的MKN45的miR-223表達(dá)水平比GT3TKB的顯著上調(diào)(P0.01)。GT3TKB在轉(zhuǎn)染miR-223的mimics后第3天增殖活性顯著上調(diào);與此相反,MKN45在轉(zhuǎn)染了miR-223的inhibitor后第3天增殖活性降低。通過(guò)轉(zhuǎn)染miR-223 mimics上調(diào)GT3TKB內(nèi)源性miR-223的表達(dá),相同倍數(shù)顯微鏡下,我們觀察到穿過(guò)侵襲小室基質(zhì)膠的轉(zhuǎn)染mimics的GT3TKB細(xì)胞比對(duì)照組GT3TKB細(xì)胞密集,數(shù)量也顯著增多(150:100;p0.01),提示侵襲能力提高。相反地,利用miR-223 inhibitor下調(diào)MKN45的miR-223表達(dá)后,其穿過(guò)基質(zhì)膠的細(xì)胞數(shù)少于對(duì)照組(150:200;p0.05),表明侵襲力下降。轉(zhuǎn)染了miR-223 mimics的GT3TKB培養(yǎng)1天后,劃痕愈合情況明顯優(yōu)于對(duì)照組,說(shuō)明miR-223提高GT3TKB的劃痕愈合速度,即轉(zhuǎn)移能力;相反,轉(zhuǎn)染了miR-223 inhibitor的MKN45在培養(yǎng)1天后,劃痕愈合情況明顯比對(duì)照組差,表明了miR-223在MKN45的劃痕愈合中起到重要作用。(4)miR-223促進(jìn)胃癌細(xì)胞遷移和侵襲的分子機(jī)制研究:結(jié)果顯示轉(zhuǎn)染了miR-223mimics的GT3TKB細(xì)胞系的PAX6表達(dá)水平顯著低于未轉(zhuǎn)染的GT3TKB對(duì)照組;而轉(zhuǎn)染了miR-223 inhibitor的MKN45細(xì)胞系的PAX6表達(dá)水平高于對(duì)照組MKN45。Western blot的實(shí)驗(yàn)也顯示出與此一致的結(jié)果:PAX6在miR-223上調(diào)的胃癌細(xì)胞中表達(dá)量下降,兩者呈負(fù)相關(guān)。結(jié)論(1)胃癌組織中差異表達(dá)的miRNA共21個(gè),差異最顯著的miRNA為miR-223、miR-20a和miR-150。(2)miR-223表達(dá)水平與腫瘤大小、TNM分期顯著相關(guān),其與轉(zhuǎn)移狀態(tài)的相關(guān)性極顯著;miR-20a與TNM分期顯著相關(guān),與轉(zhuǎn)移狀態(tài)相關(guān)性極顯著;miR-150僅與TNM分期相關(guān)性顯著。進(jìn)一步分析顯示miR-223的高表達(dá)與組織學(xué)性狀的嚴(yán)重程度和低生存率有關(guān)。(3)miR-223可促進(jìn)胃癌細(xì)胞的增殖,并促進(jìn)胃癌細(xì)胞侵襲和轉(zhuǎn)移。(4)PAX6是miR-223在胃癌細(xì)胞中的靶基因。(5)miR-223可通過(guò)下調(diào)PAX6,增強(qiáng)胃癌細(xì)胞的增殖和侵襲能力。因此,miR-223和PAX6可能成為胃癌治療的靶點(diǎn)。
[Abstract]:Background Gastric cancer is one of the most common malignant tumors in the world. In Asia, Japan, South Korea and our country are the high-risk areas of the stomach cancer, and about 400,000 new cases in our country each year, accounting for 42% of the total number of cases in the world. The 5-year survival rate of the patients with early gastric cancer can reach more than 90%, but most of the gastric cancer is in the progress of the diagnosis, or the tumor metastasis has occurred, and the 5-year survival rate is less than 30%. To reduce the mortality of gastric cancer, the most effective measure is the early detection and early treatment, the development of molecular biology provides the advanced technical means and methodology for the research of the gastric cancer mechanism, and has important guiding significance for the development of the gastric cancer treatment plan. The miRNA is a conserved non-coding small-molecule RNA of about 18-22 nucleotides, and the miRNA regulates the expression of the protein-encoding gene at the post-transcriptional or post-transcriptional level: the m-RNA is degraded or suppressed by a non-fully complementary or nearly completely complementary combination with the target gene m RNA. Since miRNAs have been found, many studies have reported the abnormal expression of miRNAs in tumor tissues, and confirmed that miRNAs have a significant correlation with some of the cancer-inhibiting factors and the cancer-promoting factors. Objective To study the correlation between the expression level and the tumor size, TNM stage and the correlation between the tumor size and TNM stage by detecting the expression of the differentially expressed miRNA in the cancer tissue and the adjacent tissue of the gastric cancer. Bioinformatics is used to predict the target gene which is the most relevant to the invasion and metastasis of gastric cancer, and how to influence the proliferation and invasion ability of gastric cancer cells through the target gene. Methods (1) In this study,3 samples of gastric cancer and non-cancerous tissue were tested, and the expression levels of 27 miRNAs screened by the previous step were verified by the q-RT-PCR method. (2) In order to explore the relationship between the development of miRNA and gastric cancer, the expression of miR-223, miR-20a and miR-150 in the sample of gastric cancer with metastasis and metastasis and the survival condition of the patient were analyzed. The expression of miR-223,-20a and-150 in 84 cases of metastatic gastric cancer and 48 non-metastatic gastric cancer samples was detected by real-time fluorescence quantitative PCR. (3) To detect the effect of miR-223 on the proliferation of gastric cancer cells, GT3TKB and MKN45 were used as the research object. First, the level of expression of miR-223 in the original GT3TKB and MKN45 was determined. The mimetics of the chemically synthesized miR-223 and the inhibitor RNA were subsequently transfected into the GT3TKB and the MKN45 cell lines, respectively. Secondly, the transwell-cell invasion experiment and the scratch-healing experiment were performed on the transfected cells. (4) In order to find the target gene of the miRNA-223, the target gene PAX6 with the largest correlation with the invasion and metastasis of the gastric cancer was selected by means of bioinformatics and according to the experience rules and the published research results. The expression level of PAX6 was detected by RT-PCR and the expression of PAX6 was detected by Western blot. The expression levels of miR-223 and PAX6 in 132 patients with gastric cancer were detected by the method of q-RT-PCR and Western blot. Results (1) The screening of differentially expressed miRNAs in gastric cancer cells showed that the expression of 13 miRNAs in gastric cancer was up-regulated and 14 miRNAs were down-regulated in gastric cancer tissues. Further validation found that 21 miRNAs were in line with the results of the chip test. Among them,10 of them were highly expressed in gastric cancer tissues and 11 were low-expression in gastric cancer tissues. The expression of 6 miRNAs was not statistically significant in gastric cancer and adjacent tissues. Among them, the most significant three miRNAs were miR-223, miR-20a and miR-150, respectively. (2) The expression of the abnormal expression of the miRNA in the tissue of the gastric cancer with metastasis and the survival analysis of the patient: The results showed that the expression of miR-223 was significantly correlated with the size of the tumor and the TNM stage (P0.05). The correlation between the expression of the miR-223 and the metastasis was very significant (P0.01), and the miR-20a was significantly related to the TNM stage (P0.05). The correlation between miR-150 and TNM was significant (P 0.01), and the correlation between miR-150 and TNM was significant (P0.05). The miR-223 expression level of 76 gastric cancer samples with severe histological characteristics was then analyzed, and the correlation between the miR-223 and the survival rate of these samples was analyzed using the Kaplan-Meier survival analysis, and the results showed that the disease-free survival rate of the miR-223 low-expression group was significantly higher than that of the miR-223 high-expression group. These results show that the expression of miR-223 is related to the development of gastric cancer. (3) The study of the effect of miR-223 on the migration and invasion of gastric cancer cells: The expression of miR-223 of MKN45 with high invasiveness was significantly up-regulated than that of GT3TKB (P0.01). The proliferation activity of MKN45 on day 3 after transfection of an inhitor of miR-223 was reduced. The expression of the endogenous miR-223 of the GT3TKB was up-regulated by transfection of miR-223 misitics, and under the same multiple microscope, we observed that the GT3TKB cells transfected with mimics, which passed through the matrix of the invasion cell, were more dense and the number of GT3TKB cells in the control group (150:100; p0.01), suggesting an increase in the invasion ability. On the contrary, after the miR-223 expression of MKN45 was down-regulated by miR-223 inhitor, the number of cells that passed through the matrix gel was less than that of the control group (150:200; p0.05), indicating a decrease in the invasion force. After 1 day after transfection of the GT3TKB of miR-223 misitics, the scratch-healing condition was better than that of the control group, which indicated that miR-223 increased the scratch-healing speed of the GT3TKB, that is, the transfer capacity; on the contrary, the MKN45 transfected with the miR-223 inhitor was significantly worse than the control group after 1 day of culture, It is shown that miR-223 plays an important role in the scratch healing of MKN45. (4) The molecular mechanism of miR-223 to promote the migration and invasion of gastric cancer cells showed that the expression of PAX6 of the GT3TKB cell line transfected with miR-223mmics was significantly lower than that of the untransfected GT3TKB control group. The expression of PAX6 in the MKN45 cell line transfected with miR-223 inhitor was higher than that of the control group (MKN45). Conclusion (1) There are 21 miRNAs differentially expressed in gastric cancer, and the most significant miRNAs are miR-223, miR-20a and miR-150. (2) The expression level of miR-223 was significantly correlated with tumor size and TNM stage, and the correlation between miR-20a and TNM was very significant, and the correlation between miR-20a and TNM was very significant; and miR-150 was associated with TNM stage only. Further analysis showed that the high expression of miR-223 was related to the severity of the histological character and the low survival rate. (3) miR-223 can promote the proliferation of gastric cancer cells and promote the invasion and metastasis of gastric cancer cells. (4) PAX6 is the target gene of miR-223 in gastric cancer cells. (5) The miR-223 can enhance the proliferation and the invasion ability of the gastric cancer cells by down-regulating the PAX6. Therefore, miR-223 and PAX6 may be the target for gastric cancer treatment.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.2

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 戴成雨;胃癌20例誤診分析[J];實(shí)用醫(yī)學(xué)雜志;2002年03期

2 李秋波,陶智慧,胡奎,韓智,馬勇;胃癌術(shù)前區(qū)域動(dòng)脈灌注化療加手術(shù)聯(lián)合治療的療效觀察(附24例)[J];航空航天醫(yī)藥;2003年03期

3 倪海濱,毛振彪,黃介飛,肖明兵,季穎林,張彥亮,冒海蕾;血清可溶性細(xì)胞間粘附分子-1與胃癌臨床意義的研究[J];南通醫(yī)學(xué)院學(xué)報(bào);2003年01期

4 邢亞莉;姚春霞;唐曉君;劉春梅;;彩超在胃癌診斷中的價(jià)值[J];基層醫(yī)學(xué)論壇;2007年17期

5 ;日本專家用新技術(shù)提高胃癌診斷準(zhǔn)確率[J];生物醫(yī)學(xué)工程與臨床;2009年02期

6 ;新技術(shù)能提高胃癌診斷準(zhǔn)確率[J];中華中醫(yī)藥學(xué)刊;2009年07期

7 高春光;;胃癌患者的臨床治療體會(huì)[J];中國(guó)民族民間醫(yī)藥;2009年14期

8 高瑞鳳;朱曄;劉興姣;;37例進(jìn)展期胃癌的超聲分析[J];中國(guó)實(shí)用醫(yī)藥;2010年25期

9 姜可偉;;規(guī)范全球第二大致死率疾病的診斷——《胃癌診斷標(biāo)準(zhǔn)》解讀[J];中國(guó)衛(wèi)生標(biāo)準(zhǔn)管理;2010年04期

10 張常華;何裕隆;詹文華;吳英;;多學(xué)科小組與胃癌診治[J];現(xiàn)代腫瘤醫(yī)學(xué);2011年06期

相關(guān)會(huì)議論文 前10條

1 武淑蘭;魏志杰;殷宇明;;胃癌致微血管病性溶血性貧血的診斷[A];第十一屆全國(guó)紅細(xì)胞疾病學(xué)術(shù)會(huì)議暨學(xué)習(xí)班論文匯編[C];2007年

2 丁濤;;超聲在診斷胃癌中的應(yīng)用[A];中國(guó)超聲醫(yī)學(xué)工程學(xué)會(huì)第三屆全國(guó)肌肉骨骼超聲醫(yī)學(xué)學(xué)術(shù)交流會(huì)論文匯編[C];2011年

3 陳曉康;呂國(guó)榮;蘇若瑟;;應(yīng)用彩色能量多普勒血流顯像對(duì)胃癌的診斷價(jià)值[A];慶祝中國(guó)超聲醫(yī)學(xué)工程學(xué)會(huì)成立20周年——第八屆全國(guó)超聲醫(yī)學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2004年

4 于吉人;;胃癌的術(shù)前系統(tǒng)評(píng)估[A];2004年浙江省外科學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2004年

5 楊軍樂(lè);寧文德;董季平;徐敏;;多層螺旋CT在胃癌診斷中的應(yīng)用研究[A];中華醫(yī)學(xué)會(huì)第十三屆全國(guó)放射學(xué)大會(huì)論文匯編（下冊(cè)）[C];2006年

6 張曉鵬;;胃癌磁共振成像研究進(jìn)展[A];第四屆中國(guó)腫瘤學(xué)術(shù)大會(huì)暨第五屆海峽兩岸腫瘤學(xué)術(shù)會(huì)議教育集[C];2006年

7 張麗紅;常維平;黃賢會(huì);;螺旋CT在特殊部位胃癌診斷中的應(yīng)用[A];中國(guó)醫(yī)師協(xié)會(huì)放射醫(yī)師分會(huì)首屆會(huì)員大會(huì)暨第四屆醫(yī)學(xué)影像山東論壇、山東省第16次放射學(xué)會(huì)議暨山東省第14屆醫(yī)學(xué)影像學(xué)學(xué)術(shù)研討會(huì)論文集[C];2007年

8 陳靜;;彩色多普勒超聲檢查在胃癌的應(yīng)用[A];中國(guó)超聲醫(yī)學(xué)工程學(xué)會(huì)第七屆全國(guó)腹部超聲學(xué)術(shù)會(huì)議學(xué)術(shù)論文匯編[C];2007年

9 劉池波;梁勇;王海寶;楊林軍;梁津逍;;胃癌患者中血清淀粉樣蛋白A的測(cè)定及臨床意義[A];第二屆中國(guó)醫(yī)學(xué)細(xì)胞生物學(xué)學(xué)術(shù)大會(huì)暨細(xì)胞生物學(xué)教學(xué)改革會(huì)議論文集[C];2008年

10 吳厚賓;;腹腔鏡在胃癌診治中的應(yīng)用進(jìn)展(綜述)[A];江西省第二屆胃腸外科學(xué)術(shù)會(huì)議暨江西省第十二次中西醫(yī)結(jié)合普通外科學(xué)術(shù)會(huì)議論文匯編[C];2012年

相關(guān)重要報(bào)紙文章 前10條

1 錢錚;新技術(shù)能提高胃癌診斷準(zhǔn)確率[N];中國(guó)中醫(yī)藥報(bào);2009年

2 記者 陳青;胃癌患者從“存活”邁向“樂(lè)活”[N];文匯報(bào);2010年

3 李楠;胃癌診斷敏感性從不足30%提高到57.4%[N];健康報(bào);2008年

4 通訊員 李楠;胃癌“轉(zhuǎn)化醫(yī)學(xué)”研究見(jiàn)成效[N];上�？萍紙�(bào);2008年

5 記者 楚燕　通訊員 那偉 高樹(shù)灼;廈門胃癌研究達(dá)國(guó)際領(lǐng)先水平[N];廈門日?qǐng)?bào);2009年

6 胡德榮;新型胃癌分子標(biāo)志物研究獲突破[N];中國(guó)醫(yī)藥報(bào);2010年

7 本報(bào)記者 周芳;改善飲食習(xí)慣 早發(fā)現(xiàn)早治療[N];吉林日?qǐng)?bào);2006年

8 中南大學(xué)湘雅二醫(yī)院 楊燕貽;胃癌防治有哪些錯(cuò)誤觀念[N];大眾衛(wèi)生報(bào);2005年

9 特約記者 程守勤;胃癌診斷又有新方法[N];家庭醫(yī)生報(bào);2003年

10 重慶萬(wàn)州 黃瓊;胃癌的手術(shù)治療[N];上海中醫(yī)藥報(bào);2013年

相關(guān)博士學(xué)位論文 前10條

1 孫大志;基于microRNA 21的調(diào)控作用探討從痰論治胃癌的作用機(jī)制[D];中國(guó)人民解放軍醫(yī)學(xué)院;2012年

2 陳悅之;TNFAIP8在胃癌中的表達(dá)和對(duì)調(diào)節(jié)胃癌細(xì)胞增殖，影響侵襲及遷移中的作用研究[D];山東大學(xué);2015年

3 殷繼鵬;腫瘤血管靶向肽GX1用于胃癌的分子影像研究[D];第四軍醫(yī)大學(xué);2015年

4 蔡習(xí)強(qiáng);TFEB介導(dǎo)的自噬在胃癌耐藥中的作用及其機(jī)制研究[D];第四軍醫(yī)大學(xué);2015年

5 趙曉迪;microRNA-7調(diào)控胃癌惡性生物學(xué)行為的功能與分子機(jī)制研究[D];第四軍醫(yī)大學(xué);2015年

6 尚華;MicroRNA-125a在胃癌中表達(dá)水平的研究及其臨床意義[D];山東大學(xué);2015年

7 關(guān)中正;TGF-β在胃癌免疫逃逸中作用及機(jī)制研究[D];山東大學(xué);2015年

8 黃勇;AEG-1/MT qDH、NF-κB、MMP-9在胃癌中的表達(dá)及相關(guān)性的研究[D];山東大學(xué);2015年

9 謝黎明;胃癌中miR-124表達(dá)的意義及作用機(jī)制研究[D];南華大學(xué);2015年

10 劉佳寧;SOX9和CEACAM1在胃癌組織中表達(dá)及其對(duì)胃癌細(xì)胞增殖和轉(zhuǎn)移的影響[D];山東大學(xué);2015年

相關(guān)碩士學(xué)位論文 前10條

1 徐海蓉;胃癌危險(xiǎn)因素的流行病學(xué)研究[D];南京醫(yī)科大學(xué);2002年

2 張軍利;p27、PTEN與VEGF蛋白在胃癌組織中的表達(dá)及其意義[D];泰山醫(yī)學(xué)院;2014年

3 馬春婷;胃癌與幽門螺桿菌的相關(guān)性研究[D];石河子大學(xué);2015年

4 王士杰;腹腔鏡手術(shù)治療進(jìn)展期遠(yuǎn)端胃癌的臨床療效及患者術(shù)后隨訪生存質(zhì)量研究[D];中國(guó)人民解放軍醫(yī)學(xué)院;2015年

5 李浩;胃癌血清蛋白標(biāo)記物的篩選與鑒定[D];鄭州大學(xué);2015年

6 王巍;胃癌患者血液樣品的光譜分析[D];鄭州大學(xué);2015年

7 李玉博;高場(chǎng)磁共振在胃癌術(shù)前T分期與分級(jí)的價(jià)值[D];鄭州大學(xué);2015年

8 張?zhí)K鈺;SOX4和P53蛋白在胃癌組織中的表達(dá)及貞芪扶正膠囊對(duì)胃癌術(shù)后輔助治療作用的觀察[D];蘭州大學(xué);2015年

9 馬來(lái)陽(yáng);能譜CT成像在胃癌術(shù)前分期及分化程度評(píng)價(jià)中的應(yīng)用研究[D];蘭州大學(xué);2015年

10 侯向紅;HORMAD2在胃癌中的表達(dá)及對(duì)胃癌細(xì)胞增殖和凋亡的影響[D];蘭州大學(xué);2015年

，

本文編號(hào)：2484961