【摘要】：目的:遠(yuǎn)處轉(zhuǎn)移是初診無轉(zhuǎn)移性鼻咽癌放化療后最主要的失敗原因,預(yù)測鼻咽癌病人遠(yuǎn)處轉(zhuǎn)移風(fēng)險是臨床研究重點(diǎn)和熱點(diǎn)。不少研究發(fā)現(xiàn)宿主本身的遺傳特質(zhì)是轉(zhuǎn)移發(fā)生發(fā)展的重要影響因素。該研究旨在探討轉(zhuǎn)化生長因子β(transforming growth factor-beta,TGF-β)信號通路中基因的單核苷酸多態(tài)性(Single Nucleotide Polymorphism,SNP)與鼻咽癌預(yù)后的關(guān)聯(lián)性。材料和方法:入組2012.01-2012.12于我院就診且經(jīng)病理確診的初診無遠(yuǎn)處轉(zhuǎn)移并且接受調(diào)強(qiáng)放射治療的患者。從外周血液標(biāo)本中提取每個患者的基因組DNA,所有血液標(biāo)本的收集均在患者接受治療前。本研究共入組鼻咽癌病例292例。本研究選擇TGF-β信號通路的5個基因12單核苷多態(tài)性位點(diǎn),采用基質(zhì)輔助激光解吸附電離飛行時間質(zhì)譜或Taq Man方法進(jìn)行SNP檢測分型。采用Kaplan Meier(KM)法計算生存率,單因素分析采用log-rank檢驗(yàn),并采用Cox比例風(fēng)險模型進(jìn)行多因素分析,探討基因多態(tài)性與鼻咽癌預(yù)后的關(guān)聯(lián)。結(jié)果:全組中位隨訪時間為39.5月(5-49月),44例出現(xiàn)了遠(yuǎn)處轉(zhuǎn)移,29例死亡。全組病人的3年無遠(yuǎn)處轉(zhuǎn)移生存率為85.0%,3年總生存率為91.2%。單因素分析發(fā)現(xiàn):TGF-β1基因rs1800469位點(diǎn)CC基因型比CT/TT型的無遠(yuǎn)處轉(zhuǎn)移生存率低(74.1%vs.87.9%,p=0.011);TGF-β1基因rs1800470位點(diǎn)的TT基因型與CT/CC型相比,TT型的無遠(yuǎn)處轉(zhuǎn)移生存率更低(72.2%vs.87.8%,p=0.004);Smad4基因rs12958604位點(diǎn)AA型的無遠(yuǎn)處轉(zhuǎn)移生存率高于AG/GG型(90.0%vs.80.6%,p=0.028),其余各SNP位點(diǎn)不同基因型患者的無轉(zhuǎn)移生存差異均未達(dá)到統(tǒng)計學(xué)差異(p0.05)。單因素也顯示rs1800469CT/TT基因型為總生存率高于CC型(93.7%vs.82.3%,p=0.010)。Cox多因素分析發(fā)現(xiàn):rs1800469位點(diǎn)CT/TT型的轉(zhuǎn)移風(fēng)險比CC型低(HR=0.539,p=0.045),rs1800470位點(diǎn)TT型的轉(zhuǎn)移風(fēng)險比CT/CC型高(HR=2.304,p=0.007),rs12958604位點(diǎn)AG/GG的轉(zhuǎn)移風(fēng)險比AA型高(HR=2.362,p=0.038);rs1800469的CT/TT基因型為死亡風(fēng)險低于CC型(HR=0.462,p=0.042)。此外,將無轉(zhuǎn)移生存存在統(tǒng)計學(xué)差異的3個位點(diǎn)結(jié)合分析發(fā)現(xiàn),同時攜帶3個高轉(zhuǎn)移風(fēng)險基因型的3年無轉(zhuǎn)移生存率為60.%,攜帶1個或2個為85.0%,無攜帶者為93.5%,差異具有統(tǒng)計學(xué)意義(p0.001)。多因素分析顯示與不攜帶不利基因型相比攜帶1個或2個不利基因型的遠(yuǎn)處轉(zhuǎn)移風(fēng)險比為2.471(p=0.090),同時攜帶3個不利基因型的風(fēng)險比為5.949(p=0.003)。結(jié)論:本研究發(fā)現(xiàn)TGF-β信號通路中存在三個單核苷酸多態(tài)性位點(diǎn)與鼻咽癌的遠(yuǎn)處轉(zhuǎn)移風(fēng)險相關(guān),rs1800469 CC基因型、rs1800470 TT基因型和rs12598604AG/GG存在較高的遠(yuǎn)處轉(zhuǎn)移風(fēng)險。聯(lián)合分析顯示能更好評估和預(yù)測鼻咽癌轉(zhuǎn)移風(fēng)險。研究也發(fā)現(xiàn)rs1800469 CC基因型是鼻咽癌總生存預(yù)后差的一個因素。這三個單核苷酸位點(diǎn)可能成為預(yù)測鼻咽癌遠(yuǎn)處轉(zhuǎn)移風(fēng)險的穩(wěn)定有效的遺傳標(biāo)記物,有待于擴(kuò)大樣本量進(jìn)一步證實(shí)及進(jìn)一步的功能實(shí)驗(yàn)驗(yàn)證。
[Abstract]:Objective: distant metastasis is the most important cause of failure after radiotherapy and chemotherapy for newly diagnosed non-metastasis nasopharyngeal carcinoma (NPC). Predicting the risk of distant metastasis in patients with nasopharyngeal carcinoma (NPC) is the focus and focus of clinical research. Many studies have found that the genetic characteristics of the host itself are an important factor affecting the occurrence and development of metastasis. The purpose of this study was to investigate the relationship between single nucleotide polymorphism (Single Nucleotide Polymorphism,SNP) of transforming growth factor 尾 (transforming growth factor-beta,TGF- 尾) signaling pathway and prognosis of nasopharyngeal carcinoma (NPC). Materials and methods: the patients who were admitted to our hospital in 2012.01 / 2012.12 and diagnosed pathologically did not have distant metastasis and received intensity modulation radiotherapy. Genomic DNA, was extracted from peripheral blood samples. All blood samples were collected before treatment. 292 cases of nasopharyngeal carcinoma (NPC) were enrolled in this study. In this study, five mononucleosides polymorphism sites of TGF- 尾 signaling pathway were selected, and SNP typing was detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry or Taq Man. The survival rate was calculated by Kaplan 鈮，

本文編號：2479720