摘要
目的探讨癌组织中O-岩藻糖基转移酶1基因(POFUT1)的表达变化对相关肿瘤预后的影响及其作用机制。方法结合TCGA数据库及GTEx数据库获取的泛癌数据集,利用GEPIA2及TIMER2数据集,比较多种类型肿瘤与配对的正常组织中POFUT1的表达水平,选出比较有统计学差异的肿瘤类型;比较不同POFUT1水平的上述肿瘤患者的预后。利用TIMER数据库及Estimate软件包筛选POFUT1与免疫细胞浸润水平关联性最强的肿瘤,并分析POFUT1与上述肿瘤组织基质评分、免疫细胞浸润评分及综合评分的相关性。进一步利用String数据库及GE⁃PIA2筛选POFUT1关联基因,并通过DAVID数据库对POFUT1及其关联基因进行信号通路富集分析。结果与配对的正常组织比较,POFUT1在胆管癌、结肠癌、乳腺癌、食管癌、胶质细胞瘤、头颈鳞状细胞癌、肾嫌色细胞癌、脑低级别胶质瘤、肝细胞癌、肺腺癌、肺鳞癌、胰腺癌、直肠腺癌、皮肤黑色素瘤、胃癌、胃食管癌、甲状腺癌组织中的表达差异具有统计学意义(P均<0.05)。POFUT1在TIMER2和GEPIA数据库中同时均表达差异的肿瘤类型有7种(结肠癌、食管癌、胶质细胞瘤、头颈鳞状细胞癌、肾嫌色细胞癌、直肠腺癌、胃癌)。肾透明细胞癌和直肠腺癌中,POFUT1高表达组的总生存期高于POFUT1低表达组(P均<0.05);脑低级别胶质瘤、间皮瘤、葡萄膜黑色素瘤中,POFUT1低表达组总生存期高于POFUT1高表达组(P均<0.05)。POFUT1与免疫细胞浸润水平关联性最强的3种肿瘤分别为脑低级别胶质瘤、结肠癌、膀胱尿路上皮癌;POFUT1表达水平与脑低级别胶质瘤组织的基质、免疫细胞浸润、综合评分及结直肠癌组织的免疫细胞浸润评分均具有相关性(P均<0.05)。POFUT1及其关联基因富集的通路主要为蛋白质结合及RNA结合途径、丝氨酸相关酶途径、细胞凋亡通路和Notch信号通路。结论POFUT1在17种肿瘤中表达水平上升;POFUT1高表达的肾透明细胞癌和直肠腺癌预后好,POFUT1低表达的脑低级别胶质瘤、间皮瘤、葡萄膜黑色素瘤预后好;POFUT1可能通过调控肿瘤免疫浸润水平及信号通路如蛋白质结合及RNA结合途径、Notch信号通路等影响肿瘤患者预后。
Objective To explore the effect of the expression changes of O-fucosyltransferase 1(POFUT1)in the tu‐mor tissues on the prognosis of tumor patients and its mechanism.Methods Combined with the pan-cancer data sets ob‐tained from the TCGA database and the GTEx database,we used the GEPIA2 and TIMER2 to compare the expression lev‐els of POFUT1 in various types of tumors and paired normal tissues,and selected the tumor types with statistical differenc‐es.The prognosis of the above tumor patients with different POFUT1 levels was compared.The TIMER database and the estimate software package were used to screen the tumors with the strongest correlation between POFUT1 and the level of immune cell infiltration,and then we analyzed the correlations between POFUT1 and the above-mentioned tumor tissue ma‐trix score,immune cell infiltration score,and comprehensive score.Further,the String database and GEPIA2 were used to screen POFUT1-related genes,and the functional enrichment analysis of POFUT1 and its related genes was carried out based on the DAVID database.Results Compared with the paired normal tissues,the expression difference of POFUT1 was statistically significant in the cholangiocarcinoma,colon cancer,breast cancer,esophageal cancer,glioblasto‐ma,head and neck squamous cell carcinoma,renal chromophobe carcinoma,low-grade brain glioma,hepatocyte cancer,lung adenocarcinoma,lung squamous cell carcinoma,pancreatic cancer,rectal adenocarcinoma,skin melanoma,gastric cancer,gastroesophageal cancer and thyroid cancer(all P<0.05).Seven tumor types showed differential expression of PO‐FUT1 in the TIMER2 and GEPIA databases(colon cancer,esophageal cancer,glioblastoma,head and neck squamous cell carcinoma,renal chromophobe carcinoma,rectal adenocarcinoma,and gastric cancer).In the renal clear cell carcino‐ma and rectal adenocarcinoma,the overall survival time of the high POFUT1 expression group was higher than that of the low POFUT1 expression group(P<0.05).In the low-grade brain glioma,mesothelioma,and uveal melanoma,the overall survival time of low POFUT1 expression group was higher than that of the high POFUT1 expression group(P<0.05).The three tumors with the strongest correlation between POFUT1 and immune cell infiltration levels were low-grade glioma,co‐lon cancer,and bladder urothelial carcinoma.The expression level of POFUT1 was related to the stroma,immune cell in‐filtration and comprehensive score of low-grade brain glioma tissues and the immune infiltration score of colorectal cancer tissues(all P<0.05).The enriched pathways of POFUT1 and its related genes were mainly protein binding and RNA bind‐ing pathway,serine-related enzyme pathway,apoptosis pathway,and Notch signaling pathway.Conclusions The ex‐pression level of POFUT1 increases in 17 types of tumors.Renal clear cell carcinoma and rectal adenocarcinoma with high POFUT1 expression have better prognosis,while low-grade brain glioma,mesothelioma and uveal melanoma with low ex‐pression have better prognosis.POFUT1 may affect the prognosis of tumor patients by regulating the level of tumor immune infiltration and signaling pathways such as protein binding,RNA binding and Notch signaling pathway.
作者
于帆
韦唯
楼爽
何海洪
周义文
YU Fan;WEI Wei;LOU Shuang;HE Haihong;ZHOU Yiwen(Clinical Laboratory Medicine Center,Shenzhen Hospital,Southern Medical University,Shenzhen 518000,China)
出处
《山东医药》
CAS
2022年第15期1-5,共5页
Shandong Medical Journal
基金
吴阶平医学基金会-临床科研专项资助基金(320.6750.2021-06-30)
南方医科大学深圳医院重点学科建设基金(ZDXKKYTS006)。
