Dataset Information

Revealing the transcriptional heterogeneity of organ-specific metastasis in human gastric cancer using single-cell RNA Sequencing.

ABSTRACT:

Background

Deciphering intra- and inter-tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) and its metastasis and identifying effective therapeutic targets. However, the characteristics of different organ-tropism metastases of GC are largely unknown.

Methods

Ten fresh human tissue samples from six patients, including primary tumour and adjacent non-tumoural samples and six metastases from different organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single-cell RNA sequencing. Validation experiments were performed using histological assays and bulk transcriptomic datasets.

Results

Malignant epithelial subclusters associated with invasion features, intraperitoneal metastasis propensity, epithelial-mesenchymal transition-induced tumour stem cell phenotypes, or dormancy-like characteristics were discovered. High expression of the first three subcluster-associated genes displayed worse overall survival than those with low expression in a GC cohort containing 407 samples. Immune and stromal cells exhibited cellular heterogeneity and created a pro-tumoural and immunosuppressive microenvironment. Furthermore, a 20-gene signature of lymph node-derived exhausted CD8⁺ T cells was acquired to forecast lymph node metastasis and validated in GC cohorts. Additionally, although anti-NKG2A (KLRC1) antibody have not been used to treat GC patients even in clinical trials, we uncovered not only malignant tumour cells but one endothelial subcluster, mucosal-associated invariant T cells, T cell-like B cells, plasmacytoid dendritic cells, macrophages, monocytes, and neutrophils may contribute to HLA-E-KLRC1/KLRC2 interaction with cytotoxic/exhausted CD8⁺ T cells and/or natural killer (NK) cells, suggesting novel clinical therapeutic opportunities in GC. Additionally, our findings suggested that PD-1 expression in CD8⁺ T cells might predict clinical responses to PD-1 blockade therapy in GC.

Conclusions

This study provided insights into heterogeneous microenvironment of GC primary tumours and organ-specific metastases and provide support for precise diagnosis and treatment.

SUBMITTER: Jiang H

PROVIDER: S-EPMC8858624 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Revealing the transcriptional heterogeneity of organ-specific metastasis in human gastric cancer using single-cell RNA Sequencing.

Jiang Haiping H Yu Dingyi D Yang Penghui P Guo Rongfang R Kong Mei M Gao Yuan Y Yu Xiongfei X Lu Xiaoyan X Fan Xiaohui X

Clinical and translational medicine 20220201 2

<h4>Background</h4>Deciphering intra- and inter-tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) and its metastasis and identifying effective therapeutic targets. However, the characteristics of different organ-tropism metastases of GC are largely unknown.<h4>Methods</h4>Ten fresh human tissue samples from six patients, including primary tumour and adjacent non-tumoural samples and six metastases from different organs or tissues (liver, peritoneum, ovary, ...[more]

PMID: 35184420

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Project description:BackgroundOrgan-specific gene expression contains rich information about in vivo biological processes. This kind of information, previously gathered through microarray profiling, has been proven fruitful to the understanding of specific mutants, regulatory events, signaling, and development. With the advent of the next-generation sequencing (NGS) of RNAs, more quantitative and detailed information of gene expressions than previously available can now be collected for each organ or organ developmental stages. The combination of an object-oriented experimental design and an efficient treatment of the high volume information generated through a NGS platform may offer a powerful tool for inferring previously intractable developmental processes.ResultsWe collected transcriptomic data over a Solexa/Illumina platform on samples of Ipomoea leaf, sepal, and petals (at three developmental stages), and presented a method for analyzing transcriptomic variations within and between organs. We demonstrated that in vivo signals of transcriptomes can be retrieved de novo through the NGS techniques, proper data handling, bioinformatic tools, and the current understanding of molecular networks. We found that numbers of transcribed genes from both nuclear and chloroplast genomes decreased by the same order of leaf → sepal →petal. Petal resembled leaf in cell division patterns and abundance level of commonly expressed organelle genes. Its chloroplast transcripts constituted a subset of those in leaf. Moreover, reconstructions of multiple metabolic networks for each organ enabled inferences of substance flow, providing transcript evidence for the path of sucrose in leaf to anthocyanin synthesis in petal.ConclusionOur results attest that developmental transcriptomes are highly informative for exploring connections between morphological traits and the associated molecular networks. Significant hypotheses have been developed, including that the petal is a derived organ of leaf and that its color can be modified by fluctuations of substance flow within the associated metabolic networks among organs.

Dataset Information

Revealing the transcriptional heterogeneity of organ-specific metastasis in human gastric cancer using single-cell RNA Sequencing.

Background

Methods

Results

Conclusions

Publications

Revealing the transcriptional heterogeneity of organ-specific metastasis in human gastric cancer using single-cell RNA Sequencing.

Similar Datasets

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