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中华细胞与干细胞杂志(电子版) ›› 2023, Vol. 13 ›› Issue (06) : 321 -330. doi: 10.3877/cma.j.issn.2095-1221.2023.06.001

论著

蛋白磷酸酶-1催化亚基β在结直肠癌诊断、预后及免疫浸润中的生物信息学分析
朱兴墅1, 郑师尧2, 王庆惠3, 陈力4, 刘旺武4, 纪辉涛3, 王瑜5, 赵虎5, 方永超5,()   
  1. 1. 350025 福州,中国人民解放军联勤保障部队第九〇〇医院普通外科;350122 福州,福建中医药大学中西医结合学院
    2. 350004 福州,福建医科大学肿瘤临床医学院
    3. 350122 福州,福建中医药大学中西医结合学院
    4. 350025 福州,福建医科大学福总临床医学院
    5. 350025 福州,中国人民解放军联勤保障部队第九〇〇医院普通外科
  • 收稿日期:2023-10-25 出版日期:2023-12-01
  • 通信作者: 方永超
  • 基金资助:
    福建省科技厅引导基金资助项目(2021Y0061)

Bioinformatics analysis of protein phosphatase-1 catalytic subunit β (PPP1CB) in colorectal cancer diagnosis, prognosis, and immune infiltration

Xingshu Zhu1, Shiyao Zheng2, Qinghui Wang3, Li Chen4, Wangwu Liu4, Huitao Ji3, Yu Wang5, Hu Zhao5, Yongchao Fang5,()   

  1. 1. Department of General Surgery, 900th Hospital of the Joint Logistics Support Force, Fuzhou 350025; College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122
    2. College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou 350004, China
    3. College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122
    4. Fuzhou General Clinical Medical College of Fujian Medical University, Fuzhou 350025
    5. Department of General Surgery, 900th Hospital of the Joint Logistics Support Force, Fuzhou 350025
  • Received:2023-10-25 Published:2023-12-01
  • Corresponding author: Yongchao Fang
引用本文:

朱兴墅, 郑师尧, 王庆惠, 陈力, 刘旺武, 纪辉涛, 王瑜, 赵虎, 方永超. 蛋白磷酸酶-1催化亚基β在结直肠癌诊断、预后及免疫浸润中的生物信息学分析[J/OL]. 中华细胞与干细胞杂志(电子版), 2023, 13(06): 321-330.

Xingshu Zhu, Shiyao Zheng, Qinghui Wang, Li Chen, Wangwu Liu, Huitao Ji, Yu Wang, Hu Zhao, Yongchao Fang. Bioinformatics analysis of protein phosphatase-1 catalytic subunit β (PPP1CB) in colorectal cancer diagnosis, prognosis, and immune infiltration[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(06): 321-330.

目的

基于生物信息学探讨蛋白磷酸酶-1催化亚基β(PPP1CB)在结直肠癌(CRC)中的表达、预后、功能富集、免疫浸润及药物敏感性分析。

方法

分别从癌症基因组图谱(TCGA)和GEO数据库GSE41258下载CRC转录组及相应临床数据。根据PPP1CB表达中位数分组,确定两组间临床数据的差异情况。利用R语言survminer包分析PPP1CB高低表达组间的生存差异;对PPP1CB表达与临床特征进行单因素和多因素Cox回归分析,筛选出影响肿瘤进展的独立预后因素;基于独立预后因素构建预测预后情况的列线图,并通过矫正曲线和ROC对模型进行内外部评估;采用R语言limma包对PPP1CB高低组进行差异分析,在DAVID数据库中进行差异表达基因(DEGs)的功能富集分析;采用R语言cibersort包进行免疫浸润丰度的评估;利用OncoPredict包进行药物敏感性预测。两组间比较采用独立样本t检验,分类变量间比较采用卡方检验。

结果

与正常组比较,PPP1CB在肿瘤组中表达降低(P < 0.001);其低表达与患者预后不良相关(P = 0.021),在M0-1和N1-2亚组的生存分析中也得到相似结果(P = 0.012,P = 0.024)。ROC曲线下面积为0.746,提示其具有良好的诊断价值。单因素和多因素Cox回归分析结果显示,PPP1CB、年龄、T分期、N分期以及M分期可作为CRC的独立预后因素。模型的矫正曲线拟合度良好,1、3和5年的ROC曲线下面积均大于0.75。在PPP1CB高低表达组中,共有303个DEGs,其中297个基因表达增加,6个基因表达降低。功能富集分析显示,该差异基因主要富集在细胞周期、细胞肌动蛋白骨架调节等多个通路。免疫细胞浸润结果显示,在两组之间存在6种免疫细胞的表达差异,其中与Treg细胞相关性最高为- 0.416。OncoPredict包进一步筛选出9种可能针对CRC的治疗药物。

结论

PPP1CB在CRC发生发展中可能扮演关键的抑癌基因角色,为CRC患者靶向治疗提供新的潜在靶点。

Objective

Using bioinformatics techniques to investigate the expression, diagnosis, prognosis, functional enrichment, immune invasion, and drug sensitivity of protein phosphatase-1 catalytic subunit β (PPP1CB) in colorectal cancer (CRC) .

Methods

The transcriptome data of CRC and corresponding clinical data were obtained from the Cancer Genome Atlas (TCGA) and GEO databases GSE41258, respectively. According to the median expression of PPP1CB, the differences in clinical data between the two groups were determined. The survival differences between the high and low expression groups of PPP1CB were analyzed using the R survminer package. Univariate and multivariate Cox regression analyses were performed using SPSS software to assess the association between PPP1CB expression and clinical features, and to identify independent prognostic factors influencing tumor progression. Based on these independent prognostic factors, a nomogram was constructed to predict prognosis, and the model was internally and externally validated using calibration curves and ROC analysis. The R limma package was utilized to analyze the differential expression of PPP1CB between high and low expression groups, and functional enrichment analysis of the differentially expressed genes (DEGs) was conducted using the DAVID database. The R language cibersort package was employed to assess the abundance of immune infiltration, while drug susceptibility prediction was performed using the OncoPredict package. The independent samples t-test was used between the two groups, and the chi-square test was used between the categorical variables.

Results

There was no significant difference in clinical data between the two groups (P > 0.05). The expression of PPP1CB in CRC exhibited a significant reduction (P < 0.001). The low expression was associated with poor patient prognosis (P = 0.021), and similar findings were observed in the survival analysis of M0-1 and N1-2 subgroups (P = 0.012, P = 0.024). The area under the ROC curve was 0.746, indicating its favourable diagnostic value. Univariate and multivariate Cox regression analysis revealed that PPP1CB, age, T stage, N stage, and M stage could serve as independent prognostic factors for CRC, leading to the construction of a nomogram. The model demonstrated a satisfactory fit, and the area under the ROC curve at 1, 3, and 5 years exceeded 0.75. Within the high and low expression groups of PPP1CB, a total of 303 DEGs, with 297 genes showing increased expression and six genes showing decreased expression. Functional enrichment analysis highlighted the enrichment of differential genes in various pathways, including cell cycle and cellular actin backbone regulation. Additionally, the immune cell infiltration analysis results indicated six differences in immune cell expression between the two groups, with the strongest correlation observed with Treg cells (- 0.416). Further utilization of the OncoPredict package identified nine potential treatments for CRC.

Conclusion

The potential role of PPP1CB as a tumor suppressor gene in the initiation and progression of CRC has been identified, presenting a novel therapeutic target for precision treatment in patients with CRC.

表1 PPP1CB高低组间差异分析[例(%)]
图1 PPP1CB在CRC中作为抑癌基因并参与独立预后因素注:a图为PPP1CB在CRC和正常组织黏膜表达差异;b图为肿瘤中PPP1CB表达与患者预后的生存分析;c图为ROC曲线确定基因的诊断价值;d ~ e图为亚组M0-M1和N1-N2的生存分析;f ~ g图为单因素和多因素Cox回归分析筛选CRC的独立预后因素
表2 单因素Cox回归分析
表3 多因素Cox回归分析
图2 预后模型构建与验证注:a图为根据多因素Cox回归分析结果构建预测CRC患者预后列线图;b ~ c图为通过矫正曲线和ROC对模型进行内部验证;d ~ e图为通过外部数据GSE41258对模型进行验证
图3 PPP1CB高低表达差异分析与功能富集分析注:a图对CRC中PPP1CB高低表达的差异基因绘制火山图;b图为100个最显著DEGs的火山图;c ~ d图为通过DAVID数据库对DEGs进行GO和KEGG富集分析
图4 PPP1CB表达与免疫细胞浸润注:a图通过cibersort算法对CRC患者中PPP1CB表达水平与免疫细胞浸润丰度进行评估;b ~ g图为免疫细胞浸润丰度与PPP1CB表达的相关性;aP < 0.05,bP < 0.01,cP < 0.001
图5 特定药物敏感性预测注:a ~ i图为通过Oncopredict包预测出PPP1CB低表达患者特异的敏感性药物;aP < 0.001
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