Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer

Zhang, Peng; Yang, Minmin; Zhang, Yiding; Xiao, Shifu; Lai, Xinxing; Tan, Aidi; Du, Shiyu; Shao, Li

doi:10.1016/j.celrep.2020.03.020

Cited by 64 publications

(86 citation statements)

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“…Our early studies also found that combination with CKI can improve the clinical effectiveness rate and performance status of radiotherapy for ESCA. Furthermore, CKI can also provide treatment by reducing gastrointestinal reactions and radiation esophagitis 13. Tumorigenesis is a complex process that is driven by a combination of networks of genes and environmental factors; there is a lack of effective methods to identify functional networks that Chinese medicine interferes with tumorigenesis [14][15][16][17] . To better analyse and predict the molecular mechanism of CKI in the treatment of ESCA, this study adopted weighted gene co-expression network analysis (WGCNA) integrated with the network pharmacology method.…”

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confidence: 99%

Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology

Zhou

Zhang

et al. 2020

Sci Rep

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compound Kushen injection (cKi), a medicine in widespread clinical use in china, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment. Esophageal cancer (ESCA) is widespread worldwide. According to Global Cancer Statistics 2018, it ranks seventh in incidence and sixth in mortality 1. The 5-year survival rate of ESCA is between 12 and 20% and differs substantially by sex 2. China is a high-risk area for ESCA, especially in some rural areas, where the incidence rate far exceeds that of urban areas due to lifestyle and environmental reasons 3. ESCA can be divided into esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) according to histological classification. In recent decades, the incidence of EAC in Western countries has increased several times, and the proportion of ESCC has exceeded 90% throughout China 4,5. The introduction of chemo(radio)therapy and surgical therapy led to increased survival rates and reduced the incidence of recurrence 6. Because conventional methods do not adequately improve patient survival of ESCA, however, scientists are seeking more effective treatments. Recently, traditional Chinese medicine (TCM) has taken the world stage as complementary and alternative medicine 7. Compound Kushen Injection (CKI) consists of two herbs, Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Smilacis Glabrae). CKI mainly contains various anticancer ingredients, such as matrine and oxymatrine, which can inhibit the growth of tumour cells, overcome resistance to metastasis and multidrug resistance, and protect human immunity 8. CKI has been utilized in clinical practice for decades to treat various solid tumour types, including liver cancer, breast cancer, gastric cancer, and other cancer types 8,9. The analysis of medical data on 2,550 ESCA patients from 22 large-scale hospitals in China confirmed that CKI has been ...

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confidence: 99%

Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology

Zhou

Zhang

et al. 2020

Sci Rep

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“…A handful of clinical trials targeting the CRC CMS4 subtype with novel immunotherapies including anti-PD-1 mAB spartalizumab [85], dual PD-1/TGFB engineered mAB-fusion protein M7824 [86], and a dendritic cell vaccine (AVEVAC) [87] have already begun in the US and EU. Similar subtyping advances in pancreatic [41], gastric [22], and liver cancers leveraging data accumulated from large-scale multicenter projects including the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and others hold similar potential.…”

Section: Tme Biomarker Concepts and Personalized Medicinementioning

confidence: 90%

“…Each of these compartments hosts a variety of cell types with varying functions. e development of single-cell RNA sequencing (scRNA-Seq) technology in recent years has vastly improved the ability to characterize these cells, and their role in cancer initiation and progression is becoming even more apparent [22]. Cancer therapies often target specific cell classes in the tumor and TME (Figure 2).…”

Section: Targeting Cell Specialization Within the Tumor Microenvironmentmentioning

confidence: 99%

Implications for Tumor Microenvironment and Epithelial Crosstalk in the Management of Gastrointestinal Cancers

Westphalen

Wee

et al. 2019

Journal of Oncology

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Rapid advances in technology are revealing previously unknown organization, cooperation, and limitations within the population of nontumor cells surrounding the tumor epithelium known as the tumor microenvironment (TME). Nowhere are these findings more pertinent than in the gastrointestinal (GI) tract where exquisite cell specialization supports a complex microenvironmental niche characterized by rapid stemness-associated cell turnover, pathogen sensing, epithelial orchestration of immune signaling, and other facets that maintain the complex balance between homeostasis, inflammation, and disease. Here, we summarize and discuss select emerging concepts in the precancerous microenvironment, TME, and tumor epithelial-TME crosstalk as well as their implications for the management of GI cancers.

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“…Single‐cell analyses in GC remains scant but is currently actively pursued . Of special mention is the recent study led by Zhang et al that mapped the single‐cell transcriptomic landscape of premalignant gastric mucosae and early gastric cancers (EGC), identifying clusters of distinct cell types and their unique molecular features at each stage. By investigating the expression profiles of the conserved antral basal gland mucous cell type across different stages of the lesion, the team discovered the acquisition of an intestinal‐like stem cell phenotype that could be central in tumorigenesis.…”

Section: Confounding Layers Of Complexities Underlie Gc Classificationmentioning

confidence: 99%

Dissection of gastric cancer heterogeneity for precision oncology

Tan

2019

Cancer Science

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Gastric cancer (GC) remains the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. Comprehensive ‐omic studies have unveiled a heterogeneous GC landscape, with considerable molecular diversity both between and within tumors. Given the complex nature of GC, a long‐sought goal includes effective identification of distinct patient subsets with prognostic and/or predictive outcomes to enable tailoring of specific treatments (“precision oncology”). In this review, we highlight various approaches to molecular classification in GC, covering recent genomic, transcriptomic, proteomic and epigenomic features. We pay special attention to the translational significance of classifier systems and examine potential confounding factors which deserve further investigation. In particular, we discuss recent advancements in our knowledge of intra‐subtype, intra‐patient and intra‐tumor heterogeneity, and the pivotal role of the tumor stromal microenvironment.

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Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer

Cited by 64 publications

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Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology

Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology

Implications for Tumor Microenvironment and Epithelial Crosstalk in the Management of Gastrointestinal Cancers

Dissection of gastric cancer heterogeneity for precision oncology

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