印戒细胞癌(signet ring cell carcinoma,SRCC)是结直肠癌(colorectal cancer,CRC)中一类少见但特征明显的病理亚型,其具有富含黏液的表型,且转移率较高、预后较差.本课题组的CRC单细胞RNA测序(single-cell RNA sequencing,scRNA-seq)队列中,招募了 1例该病例,是目前世界上首例来源于结直肠SRCC的scRNA-seq数据.本文基于这一批scRNA-seq数据及其他公开数据,探索了 SRCC与常见腺癌(adenocarcinoma,AC)之间的细胞和分子生物学差异.结果提示,SRCC中杯状细胞样的恶性细胞是导致其独特表型的原因,这些细胞特异性上调蛋白质加工处理和细胞黏附相关信号通路,并高表达多种黏蛋白基因;上皮间充质转换(epithelial to mesenchymal transition,EMT)与CRC转移相关.SRCC具有不同于AC的EMT基因表达谱,SRCC被证明具有高水平的EMT,这也与它们的高恶性程度相一致;结合肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)数据库中CRC转录组数据和随访信息,EMT相关基因存在潜在预后作用;与AC相比,SRCC中淋巴细胞的占比较低,髓系细胞占比较高,且上皮细胞与免疫细胞的相关性降低;CRC中上皮细胞与基质细胞间广泛存在胶原蛋白和整合素的相互作用.该研究首次报道了结直肠SRCC的单细胞转录组图谱,是对近年来CRC单细胞图谱的有力补充,为寻找结直肠SRCC的治疗靶点提供新的思路.
Single-cell sequencing reveals the cellular and molecular biological features of signet colorectal ring cell carcinoma
Signet ring cell carcinoma(SRCC)is a rare but distinctive pathological subtype of colorectal cancer(CRC)with a mucin-rich phenotype as well as high metastatic rate and poor prognosis.In our large cohort of single-cell RNA sequencing(scRNA-seq)study of CRC,one case of SRCC was serendipitously enrolled.It is currently the first scRNA-seq data of SRCC derived from CRC in the world.Using this batch of scRNA-seq data including the SRCC,we aimed to compare the SRCC case with common adenocarcinoma(AC)in order to elucidate the cellular and molecular mechanisms behind SRCC.The results sug-gested that goblet-like malignant cells in SRCC contributed to its unique phenotypes.These cells specifically upregulated protein processing and cell adhesion related signaling pathways and overexpressed multiple mucin genes.Epithelial to mesenchymal transition(EMT)was associated with CRC metastasis.SRCC exhibited high level of EMT,in accordance with its high malig-nancy.However,the EMT related genes in SRCC were different from those of common AC.The potential prognostic role of genes related to EMT was revealed by combining the transcriptomic data and follow-up information of CRC in The Cancer Genome Atlas(TCGA)database.Compared to AC,SRCC had a smaller proportion of lymphocytes and a larger proportion of myeloid cells,and the correlation between epithelial and immune cells was reduced.Collagen and integrins interacted extensive-ly between epithelial cells and stromal cells in CRC.This study is the first to characterize colorectal SRCC at the single cell level which is a powerful complement to the single-cell atlas of CRC,and provides new insights into the therapeutic targets of color-ectal SRCC.
colorectal signet ring cell carcinomacolorectal adenocarcinomasingle-cell RNA sequencingtumor metastasisepithelial to mesenchymal transition
NETL
NSTL
万方数据
