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中华普通外科学文献(电子版) ›› 2023, Vol. 17 ›› Issue (04) : 271 -277. doi: 10.3877/cma.j.issn.1674-0793.2023.04.007

论著

补体3在乳腺癌中的表达差异及临床意义的生物信息学分析
张琴琴, 王俊楠, 林厚民, 伍莹, 谭月梅, 李明洲, 金俊飞, 王宁霞, 洪勇()   
  1. 541002 桂林,广西壮族自治区南溪山医院甲状腺乳腺外科;510630 广州,暨南大学附属第一医院乳腺外科
    541000 桂林,桂林医学院
    530008 桂林,广西肝损伤与修复分子医学重点实验室
    541002 桂林,广西壮族自治区南溪山医院甲状腺乳腺外科
    530008 桂林,广西肝损伤与修复分子医学重点实验室;541001 桂林,桂林医学院附属医院
    510630 广州,暨南大学附属第一医院乳腺外科
  • 收稿日期:2022-12-29 出版日期:2023-08-01
  • 通信作者: 洪勇
  • 基金资助:
    广西自然科学基金面上项目(2020GXNSFAA159051); 广西肝脏损伤与修复分子医学重点实验室经费开放课题(GXLIRMMKL-201915); 广西医疗卫生适宜技术开发与推广应用项目(S2020068); 桂林市临床重点专科建设项目(市卫医〔2019〕36号); 广西医疗卫生重点培育学科建设项目(桂卫医发〔2022〕17号)

Bioinformatics analysis of differential expression and clinical significance of complement 3 in breast cancer

Qinqin Zhang, Junnan Wang, Houmin Lin, Ying Wu, Yuemei Tan, Mingzhou Li, Junfei Jin, Ningxia Wang, Yong Hong()   

  1. Department of Thyroid and Breast Surgery, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541002, China; Department of Breast Surgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China
    Guilin Medical University, Guilin 541000, China
    Guangxi Laboratory Molecular Medicine in Liver Injury and Repair, Guilin 530008, China
    Department of Thyroid and Breast Surgery, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541002, China
    Guangxi Laboratory Molecular Medicine in Liver Injury and Repair, Guilin 530008, China; Affiliated Hospital of Guilin Medical University, Guilin 541001, China
    Department of Breast Surgery, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China
  • Received:2022-12-29 Published:2023-08-01
  • Corresponding author: Yong Hong
引用本文:

张琴琴, 王俊楠, 林厚民, 伍莹, 谭月梅, 李明洲, 金俊飞, 王宁霞, 洪勇. 补体3在乳腺癌中的表达差异及临床意义的生物信息学分析[J]. 中华普通外科学文献(电子版), 2023, 17(04): 271-277.

Qinqin Zhang, Junnan Wang, Houmin Lin, Ying Wu, Yuemei Tan, Mingzhou Li, Junfei Jin, Ningxia Wang, Yong Hong. Bioinformatics analysis of differential expression and clinical significance of complement 3 in breast cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(04): 271-277.

目的

初步探究补体3(C3)在乳腺癌中的表达、预后评估价值、相关作用及潜在机制,为后期相关研究提供依据。

方法

使用TCGA、Breast Cancer Gene-Expression Miner、UALCAN、CPTAC、TIMER、Kaplan-Meier Plotter、GeneMANIA、DAVID等多个数据库对C3在泛癌中的表达、临床特征关系、预后价值、免疫相关性等进行综合分析,随后在乳腺癌中进行单基因差异分析,并进一步对C3在不同分型的乳腺癌做免疫细胞浸润相关性分析。

结果

TCGA数据库分析显示,C3在多种恶性肿瘤中的表达存在显著差异,并且与临床分期及预后相关;把表达差异、预后相关、临床分期相关取交集后发现C3在肾透明细胞癌、混合型肾癌、甲状腺癌、乳腺浸润癌、肝细胞癌5种肿瘤中呈现出表达差异,与预后及临床分期相关。C3在乳腺癌中为低表达;而癌组织中C3 mRNA水平与预后呈正相关,在非配对及配对分析中发现C3在乳腺癌组织中的表达均低于正常乳腺组织,其差异均具有统计学意义(P<0.001)。Survfit函数分析结果显示,C3低表达组和高表达组患者的总生存期(OS)预后差异有统计学意义(P=0.01),低C3表达水平与较短的OS相关。利用UALCAN平台分析C3 mRNA水平并绘制生存曲线,结果显示C3水平对乳腺癌有特异性诊断价值。TIMER数据库分析显示,C3在各种分型的乳腺癌中均与免疫细胞浸润呈正相关。

结论

C3在乳腺癌中低表达,有预后评估价值及特异性诊断价值,影响乳腺癌预后,机制可能与C3相关的免疫细胞浸润有关。补体通过肿瘤微环境对肿瘤免疫发挥重要作用。

Objective

To explore the expression, prognosis, function, underlying mechanisms and significance of complement 3 (C3) in breast cancer, and to provide basis for further research on the mechanism of C3 in breast cancer.

Methods

TCGA, Breast Cancer Gene-Expression Miner, UALCAN, CPTAC, TIMER, Kaplan-Meier Plotter, GeneMANIA, DAVID were used for comprehensive analysis of the expression of C3 in the generic cancer, clinical features, prognostic value, and correlation immune. And then single genetic analysis was carried out by collecting clinical tissue samples for further validation.

Results

TCGA database analysis showed that there were significant differences in the expression of C3 in various malignant tumors, and it was correlated with clinical stage and prognosis. After the intersection of expression difference, prognostic correlation and clinical stage correlation, it was found that C3 had significant differences in kidney renal clear cell carcinoma, pan-kidney cohort (KICH+KIRC+KIRP), thyroid carcinoma, breast invasive carcinoma, and hepatocellular carcinoma, which were related to prognosis and clinical stage. C3 was lowly expressed in breast cancer. The mRNA level of C3 in cancer tissues was positively correlated with the prognosis of breast cancer. The expression of C3 in breast cancer tissues was lower than that in normal breast tissues in both unpaired and paired analyses, and the differences were statistically significant (both P<0.001). The results of Survfit function showed that there was significantly prognostic difference in overall survival (OS) between patients with low and high C3 expression (P=0.01), and low C3 expression level was associated with shorter OS in cancers. The level of C3 mRNA was analyzed by UALCAN platform and the ROC curve was drawn. The results showed that C3 level had specific diagnostic value for breast cancer. TIMER database analysis showed that C3 was positively correlated with immune cell infiltration in all types of breast cancer.

Conclusions

C3 is lowly expressed in breast cancer, which has prognostic value and specific diagnostic value. C3 plays a role in breast cancer and affects the prognosis, and the mechanism may be related to C3-related immune cell infiltration. Complement plays an important role in tumor immunity through tumor microenvironment.

图1 C3在泛癌中表达、预后相关性、临床相关性分析 A为TCGA数据库中不同肿瘤和对应的正常组织中C3 mRNA的表达水平,红色代表肿瘤,蓝色代表与其相对应的正常组织;B为C3 mRNA水平和14种肿瘤患者预后显著相关的森林图;C为C3 mRNA水平在与9种肿瘤患者临床分期显著相关;D为Ven图示C3在泛癌中有表达差异,并在预后、临床分期有显著差异的肿瘤类型取交集后获得HCC、BRCA、THCA、KIRC、KIPAN 5种肿瘤类型(*P<0.05,**P<0.01,***P<0.001)
图2 C3 mRNA表达及其与乳腺癌预后相关性 A为仙桃学术平台生信分析TCGA中C3在乳腺癌和正常乳腺组织表达情况非配对检验;B为配对检验;C~F为SangerBox"Gene-KM plotter"模块中C3 mRNA的表达水平与乳腺癌预后的关系,Kaplan-Meier绘图仪进行生存分析,其中C为总生存期,D为无病间期,E为疾病特异生存期,F为无进展间隔期
图3 C3在乳腺癌中蛋白表达水平 A为CAPT数据库分析乳腺癌中C3蛋白水平下降;B为C3 mRNA水平对乳腺癌预测的ROC曲线图
图4 基于TIMER数据库分析乳腺癌组织中C3的表达与免疫细胞浸润水平呈正相关 A为C3与肿瘤纯度相关性;B为C3与B细胞相关性;C为C3与CD8+ T细胞相关性;D为C3与CD4+ T细胞相关性;E为C3与巨噬细胞相关性;F为C3与中性粒细胞相关性;G为C3与树突状细胞相关性
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