Zhang Guo-Liang, Pan Le-Lin, Huang Tao, Wang Jin-Hai
Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China.
Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
J Cancer. 2019 Oct 11;10(23):5883-5890. doi: 10.7150/jca.32267. eCollection 2019.
The previous cancer studies were difficult to reproduce since the tumor tissues were analyzed directly. But the tumor tissues were actually a mixture of different cancer cells. The transcriptome of single-cell was much robust than the transcriptome of a mixed tissue. The single-cell transcriptome had much smaller variance. In this study, we analyzed the single-cell transcriptome of 272 colorectal cancer (CRC) epithelial cells and 160 normal epithelial cells and identified 342 discriminative transcripts using advanced machine learning methods. The most discriminative transcripts were LGALS4, PHGR1, C15orf48, HEPACAM2, PERP, FABP1, FCGBP, MT1G, TSPAN1 and CKB. We further clustered the 342 transcripts into two categories. The upregulated transcripts in CRC epithelial cells were significantly enriched in Ribosome, Protein processing in endoplasmic reticulum, Antigen processing and presentation and p53 signaling pathway. The downregulated transcripts in CRC epithelial cells were significantly enriched in Mineral absorption, Aldosterone-regulated sodium reabsorption and Oxidative phosphorylation pathways. The biological analysis of the discriminative transcripts revealed the possible mechanism of colorectal cancer.
以往的癌症研究很难重复，因为是直接对肿瘤组织进行分析。但肿瘤组织实际上是不同癌细胞的混合物。单细胞转录组比混合组织的转录组更稳定。单细胞转录组的方差要小得多。在本研究中，我们分析了272个结肠直肠癌（CRC）上皮细胞和160个正常上皮细胞的单细胞转录组，并使用先进的机器学习方法鉴定出342个具有鉴别性的转录本。最具鉴别性的转录本是LGALS4、PHGR1、C15orf48、HEPACAM2、PERP、FABP1、FCGBP、MT1G、TSPAN1和CKB。我们进一步将这342个转录本聚类为两类。CRC上皮细胞中上调的转录本在核糖体、内质网中的蛋白质加工、抗原加工和呈递以及p53信号通路中显著富集。CRC上皮细胞中下调的转录本在矿物质吸收、醛固酮调节的钠重吸收和氧化磷酸化途径中显著富集。对具有鉴别性的转录本进行生物学分析揭示了结肠癌的可能机制。
