本文選題：糖酵解 + 代謝重編��； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:代謝重編是腫瘤發(fā)生的主要特征之一,腫瘤細(xì)胞通過重整代謝促進(jìn)腫瘤增殖、侵襲和轉(zhuǎn)移。因此,本文通過免疫組織化學(xué)染色分析不同代謝標(biāo)記物的表達(dá)情況來闡明喉鱗狀細(xì)胞癌(Laryngeal squamous cell carcinoma,LSCC)組織的代謝狀態(tài)及不同代謝模式又是如何促進(jìn)腫瘤存活與惡變。方法:收集2014年12月至2016年12月經(jīng)手術(shù)切除的50例喉鱗狀細(xì)胞癌組織及10例癌旁組織,并對(duì)臨床資料進(jìn)行整理分析。應(yīng)用免疫組織化學(xué)方法檢測不同代謝標(biāo)記物在喉鱗狀細(xì)胞癌組織及癌旁組織中的表達(dá)情況,評(píng)估不同代謝物之間的相關(guān)性及它們與臨床病理學(xué)資料的關(guān)系。我們根據(jù)樣本的特點(diǎn)采用卡方或者Fisher’s確切概率的檢驗(yàn)方法通過SPSS21.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)分析;不同代謝標(biāo)記物之間的相關(guān)性則用Spearman等級(jí)相關(guān)來分析。通過雙側(cè)檢驗(yàn),所測結(jié)果以P0.05認(rèn)為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1單羧酸轉(zhuǎn)運(yùn)體4(Monocarboxylate transporter-4,MCT-4)幾乎不在正常粘膜組織表達(dá),而單羧酸轉(zhuǎn)運(yùn)體1(Monocarboxylate transporter-1,MCT-1)和F1-ATP合酶β亞單位(F1-ATPase beta-subunit,β-F1-ATPase)主要在正常組織中具有干細(xì)胞活性的基底細(xì)胞層表達(dá)。在喉鱗狀細(xì)胞癌組織中MCT-1、MCT-4、線粒體外膜轉(zhuǎn)位酶20(Translocase of outer mitochondrial membrane 20,TOMM20)、β-F1-ATPase、碳酸酐酶Ⅸ(Carbonic anhydraseⅨ,CAⅨ)和過氧化物氧化還原蛋白1(Peroxiredoxin-1,PRDX-1)的陽性表達(dá)率分別為74.0%、66.0%、70.0%、78.0%、64.0%、70.0%。通過統(tǒng)計(jì)分析,我們發(fā)現(xiàn)不同標(biāo)記物的陽性表達(dá)率在喉鱗狀細(xì)胞癌組織和癌旁組織中組間差異均有統(tǒng)計(jì)學(xué)意義(PMCT-1=0.007;PMCT-4=0.001;PTOMM20=0.017;Pβ-F1-ATPase=0.015;PCAⅨ=0.010;PPRDX-1=0.017)。2在50例喉鱗狀細(xì)胞癌組織中mct-1,tomm20,β-f1-atpase和prdx-1陽性表達(dá)率在不同病理分級(jí)和臨床分期的分組中組間差異均有統(tǒng)計(jì)學(xué)意義(pmct-1,病理分級(jí)=0.001,pmct-1,臨床分期=0.003;ptomm20,病理分級(jí)=0.012,ptomm20,臨床分期=0.021;pβ-f1-atpase,病理分級(jí)=0.031,pβ-f1-atpase,臨床分期=0.046;pprdx-1,病理分級(jí)=0.012,pprdx-1,臨床分期=0.021)。此外,mct-1和prdx-1陽性表達(dá)率在有無淋巴結(jié)轉(zhuǎn)移的分組中組間差異有統(tǒng)計(jì)學(xué)意義(pmct-1,淋巴結(jié)轉(zhuǎn)移=0.047;pprdx-1,淋巴結(jié)轉(zhuǎn)移=0.043),tomm20陽性表達(dá)率在不同吸煙量分組中的組間差異有統(tǒng)計(jì)學(xué)意義(ptomm20,吸煙量=0.019)。同時(shí),mct-4和caⅨ陽性表達(dá)率在不同病理分級(jí)分組中的陽性表達(dá)組間差異均有統(tǒng)計(jì)學(xué)意義(pmct-4,病理分級(jí)=0.003;pcaⅨ,病理分級(jí)=0.022)。3通過免疫組織化學(xué)染色,我們更直觀地發(fā)現(xiàn)線粒體氧化磷酸化相關(guān)標(biāo)記物主要在腫瘤實(shí)質(zhì)表達(dá),并且可以選擇性進(jìn)行擴(kuò)增。而在相鄰腫瘤間質(zhì)中表達(dá)較低甚至缺失。腫瘤分化程度越差、惡性程度越高線粒體氧化磷酸化相關(guān)標(biāo)記物的陽性表達(dá)水平就越高。在高分化的腫瘤中線粒體氧化磷酸化相關(guān)標(biāo)記物主要在癌巢侵襲性的前端表達(dá),在低分化的腫瘤中則呈成彌漫性高表達(dá)。相反,糖酵解標(biāo)記物mct-4可以在腫瘤實(shí)質(zhì)和腫瘤間質(zhì)表達(dá),在腫瘤實(shí)質(zhì)中,糖酵解標(biāo)記物mct-4主要在高分化的腫瘤組織和肥胖衰老退變的腫瘤組織中表達(dá);在腫瘤間質(zhì)中,mct-4始終在腫瘤相關(guān)成纖維細(xì)胞和炎癥細(xì)胞中表達(dá)。4我們應(yīng)用spearman等級(jí)相關(guān)來分析糖酵解和線粒體氧化磷酸化標(biāo)記物在喉鱗狀細(xì)胞癌中表達(dá)的相關(guān)性。其中,mct-1、tomm20、β-f1-atpase和prdx-1四者之間呈正相關(guān),此外,mct-4、caⅨ和prdx-1三者之間呈正相關(guān)。結(jié)論:1在正常組織中,具有干細(xì)胞活性的基底細(xì)胞層與l-乳酸、酮類物質(zhì)的高攝取和線粒體氧化磷酸化代謝相關(guān):mct-1和β-f1-atpase是基底細(xì)胞層的標(biāo)記物。2結(jié)果證實(shí):在喉鱗狀細(xì)胞癌組織中我們幾乎未見mct-4(+)且tomm20(-)的傳統(tǒng)“糖酵解”腫瘤細(xì)胞,表明喉鱗狀細(xì)胞癌中可能不存在傳統(tǒng)的“warburgeffect”。但是,腫瘤實(shí)質(zhì)可以進(jìn)行線粒體氧化磷酸化擴(kuò)增,誘導(dǎo)相鄰間質(zhì)進(jìn)行糖酵解。這意味著糖酵解和線粒體氧化磷酸化在喉鱗狀細(xì)胞癌中同時(shí)存在,協(xié)同促進(jìn)腫瘤增殖、侵襲和轉(zhuǎn)移。3靶向線粒體氧化磷酸化和糖酵解相關(guān)蛋白可以為腫瘤學(xué)的診斷和治療提供新的思路,應(yīng)開發(fā)應(yīng)用于腫瘤的個(gè)體化治療中。這或許是延緩腫瘤進(jìn)展、降低治療抵抗和提高療效的有效手段。
[Abstract]:Objective: metabolic rearrangement is one of the main characteristics of tumor occurrence. Tumor cells promote tumor proliferation, invasion and metastasis through renormalization. Therefore, the metabolic status of Laryngeal squamous cell carcinoma (LSCC) tissue is elucidated by immunohistochemical staining analysis of the expression of different metabolic markers. Different metabolic patterns promote tumor survival and malignancy. Methods: 50 cases of laryngeal squamous cell carcinoma (laryngeal squamous cell carcinoma) and 10 para cancerous tissues were collected from December 2014 to 2016, and the clinical data were collected and analyzed. Immunohistochemistry was used to detect different metabolic markers in the tissues of squamous cell carcinoma of the larynx and the para cancer group. The correlation between the different metabolites and their relationship with the clinicopathological data was evaluated. We used the statistical analysis of the chi square or Fisher 's's exact probabilities through the SPSS21.0 statistical software according to the characteristics of the samples; the correlation between the different metabolic markers was related to the Spearman level correlation. Analysis. Through bilateral tests, the results were found to be statistically significant with P0.05. Results: 1 mono carboxylic transporter 4 (Monocarboxylate transporter-4, MCT-4) was almost not expressed in normal mucous tissue, while mono carboxylic transporter 1 (Monocarboxylate transporter-1, MCT-1) and F1-ATP synthase beta subunit (F1-ATPase beta-subunit, beta -F1-ATPase) MCT-1, MCT-4, mitochondrial epicardial transposition enzyme 20 (Translocase of outer mitochondrial membrane 20, TOMM20), beta -F1-ATPase, carbonic anhydrase IX (Carbonic anhydrase IX, CA IX) and peroxide redox protein 1 in laryngeal squamous cell carcinoma tissue. The positive expression rates of n-1, PRDX-1) were 74%, 66%, 70%, 78%, 64%, and 64%. Through statistical analysis, we found that the positive rates of different markers were statistically significant (PMCT-1=0.007; PMCT-4=0.001; PTOMM20=0.017; P beta -F1-ATPase=0.015; PCA IX =0.010; PPRDX-1=0). .017) the positive expression rates of MCT-1, tomm20, beta -f1-atpase and prdx-1 in 50 cases of laryngeal squamous cell carcinoma were statistically significant in different pathological grades and clinical stages (pmct-1, pmct-1, pmct-1, clinical stage =0.003, ptomm20, pathogenesis, clinical staging, pathology, pathology, pathology, pathology, pathology, and pathology. =0.031, P beta -f1-atpase, clinical staging =0.046; pprdx-1, pathological grading =0.012, pprdx-1, clinical stage =0.021). Moreover, the positive rates of MCT-1 and prdx-1 were statistically significant (pmct-1, lymph node metastasis =0.047; lymph node metastasis). There were statistical significance (ptomm20, smoking =0.019) in the smoke volume group. At the same time, the positive expression rates of mct-4 and CA IX positive expression rates in different pathological classification groups were statistically significant (pmct-4, pathological grading =0.003; PCA IX, pathological grading =0.022).3 through immunohistochemical staining, we more intuitively found Mitochondrial oxidative phosphorylation related markers are mainly expressed in tumor substance and can be selectively amplified. The lower or even deletion in adjacent tumor interstitium. The worse the tumor differentiation, the higher the degree of malignancy the higher the positive expression level of mitochondrial oxidative phosphorylation related markers. Mitochondria in highly differentiated tumors Oxidative phosphorylation related markers are mainly expressed in the front-end of the invasion of cancer nests, and diffuse high expression in low differentiated tumors. On the contrary, glycolytic marker mct-4 can be expressed in tumor substance and tumor interstitium. In tumor substance, glycolytic marker mct-4 is mainly in highly differentiated tumor tissue and the swelling of obesity and senescence. Expression in tumor tissue; in the tumor interstitium, mct-4 is always expressed in tumor related fibroblasts and inflammatory cells. We use Spearman correlation to analyze the correlation between glycolysis and mitochondrial oxidative phosphorylation markers in laryngeal squamous cell carcinoma. Among them, there is a positive correlation between MCT-1, tomm20, beta -f1-atpase and prdx-1 four. In addition, there is a positive correlation between mct-4, CA IX and prdx-1 three. Conclusion: 1 in normal tissues, the basal cell layer with stem cell activity is related to the high uptake of l-, the high uptake of ketone substances and mitochondrial oxidative phosphorylation: MCT-1 and beta -f1-atpase are the markers of the basal cell layer,.2 results, which are confirmed in the laryngeal squamous cell carcinoma tissue. There is no traditional "glycolysis" tumor cells of mct-4 (+) and tomm20 (-), indicating that there may be no traditional "warburgeffect" in laryngeal squamous cell carcinoma. However, the tumor substance can be amplified by oxidative phosphorylation of mitochondria to induce glycolysis in adjacent stroma, which means glycolysis and mitochondrial oxidative phosphorylation in laryngeal squamous cells. The simultaneous existence of cancer, synergistic promotion of tumor proliferation, invasion and metastasis of.3 targeted mitochondrial oxidative phosphorylation and glycolysis related proteins can provide new ideas for the diagnosis and treatment of oncology, and should be developed in the individualized treatment of tumors. This may be an effective means of slowing down the progress of the tumor, reducing the resistance to treatment and improving the efficacy.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.65

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Minjong Lee;Jung-Hwan Yoon;;Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication[J];World Journal of Biological Chemistry;2015年03期

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本文編號(hào)：1892630