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9 results on '"Wangkai Xie"'

1. Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor

Author

Chenchen Mao, Yanyu Chen, Dong Xing, Teming Zhang, Yangxuan Lin, Cong Long, Jiaye Yu, Yunhui Luo, Tao Ming, Wangkai Xie, Zheng Han, Dianfeng Mei, Dan Xiang, Mingdong Lu, Xian Shen, and Xiangyang Xue

Subjects
single-cell RNA-sequencing, spatial transcriptomics, colon cancer liver metastasis, natural killer cells, Medicine, Science, Biology (General), QH301-705.5
Abstract

The abundance and biological contribution of natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM). Here, we integrated single-cell RNA-sequencing, spatial transcriptomics (ST), and bulk RNA-sequencing datasets to investigate NK cells’ biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. Useing single-cell RNA-sequencing and ST, we mapped the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. In summary, our findings revealed resting NK cells exhibited a clinical relevance with CCLM, which may be exploited for novel strategies to improve therapeutic outcomes for patients with CCLM.

Published
2024
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2. ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer

Author

Wangkai Xie, Zheng Han, Ziyi Zuo, Dong Xin, Hua Chen, Juanjuan Huang, Siyu Zhu, Han Lou, Zhiqiang Yu, Chenbin Chen, Sian Chen, Yuanbo Hu, Jingjing Huang, Fabiao Zhang, Zhonglin Ni, Xian Shen, Xiangyang Xue, and Kezhi Lin

Subjects
Cytology, QH573-671
Abstract

Abstract Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.

Published
2023
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3. The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer

Author

Sisi Ye, Yuanbo Hu, Chenbin Chen, Sian Chen, Xinya Tong, Huanbo Zhu, Bo Deng, Xianjing Hu, Xiangwei Sun, Xiaodong Chen, Xinyu Shi, Ruihong Gu, Wangkai Xie, Gangqiang Guo, Dong Xing, Xian Shen, Xiangyang Xue, and Shurong Shen

Subjects
human cytomegalovirus, gastric cancer, US31, tumor immune microenvironment, prognostic factor, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.

Published
2021
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4. Three-Dimensional Ex Vivo Culture for Drug Responses of Patient-Derived Gastric Cancer Tissue

Author

Sian Chen, Chenbin Chen, Yuanbo Hu, Ce Zhu, Xiaozhi Luo, Lizhu Wang, Xiang Wang, Xiangwei Sun, Xiaodong Chen, Wangkai Xie, Han Lou, Xielin Huang, Chao Li, Jun Xu, Xiangyang Xue, and Xian Shen

Subjects
gastric cancer, ex vivo tumor tissue culture, proliferation, apoptosis, chemotherapy effectiveness, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Gastric cancer (GC) is one of the most common malignancies with high mortality and substantial morbidity. Although the traditional treatment strategies for GC revolve around surgery, radiotherapy, and chemotherapy, none have been able to optimally treat most affected patients. To improve clinical outcomes and overcome potential GC resistance, we established a three-dimensional (3D) culturing platform that accurately predicts drug responses in a time- and cost-effective manner. We collected tumor tissues from patients following surgeries and cultured them for 3 days using our protocol. We first evaluated cell proliferation, viability, and apoptosis using the following markers: Ki67 and cleaved caspase 3 (Cas3). We demonstrated that cell viability was maintained for 72 h in culture and that the tumor microenvironments and vascular integrities of the tissues were intact throughout the culture period. We then administered chemotherapeutics to assess drug responses and found differential sensitivity across different patient-derived tissues, enabling us to determine individualized medication plans. Overall, our study validated this rapid, cost-effective, scalable, and reproducible protocol for GC tissue culture that can be employed for drug response assessments. Our 3D culture platform paves a new way for personalized medication in GC and other tumors and can greatly impact future oncological research.

Published
2021
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5. Overexpression of the human cytomegalovirus UL111A is correlated with favorable survival of patients with gastric cancer and changes T-cell infiltration and suppresses carcinogenesis

Author

Kangming Lin, Changyuan Hu, Xielin Huang, Xian Shen, Xin Liu, Ning Ding, Wangkai Xie, Yingpeng Huang, Dan Xiang, and Xiangyang Xue

Subjects
Adult, Male, 0301 basic medicine, Human cytomegalovirus, Cancer Research, Carcinogenesis, T-Lymphocytes, Cytomegalovirus, Biology, medicine.disease_cause, UL111A gene, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Viral Envelope Proteins, Stomach Neoplasms, medicine, Humans, Tissue microarray, Cell growth, FOXP3, General Medicine, Middle Aged, Prognosis, medicine.disease, 030104 developmental biology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cytomegalovirus Infections, Cancer research, Immunohistochemistry, Female, Original Article – Cancer Research, Gastric cancer, CD8, Infiltrating immune cells
Abstract

Purpose We previously found that human cytomegalovirus (HCMV) infection is associated with gastric cancer (GC) development. UL111A plays a role during HCMV productive or latent infection. However, UL111A expression profiles in GC tissues and their relationship with this disease are unknown. Methods PCR and nested RT-PCR were performed to verify UL111A expression in 71 GC tissues and its transcripts in 16 UL111A-positive GC samples. UL111A expression levels in GC patients were evaluated by immunohistochemistry on a tissue microarray for 620 GC patients. The correlations among UL111A expression levels, clinicopathological characteristics, and prognosis were analyzed. Further, the effects of overexpression of latency-associated viral interleukin-10 (LAcmvIL-10) and cmvIL-10 on GC cell proliferation, colony formation, migration, and invasion were assessed. Results The UL111A detection rate in GC tissues was 32.4% (23/71) and that of its mRNA expression was 68.75% (11/16). High expression of UL111A was also related to better overall and disease-free survival in GC patients. GC patients with TNM II/III stage expressing higher UL111A levels might benefit from adjuvant chemotherapy (ACT) after surgery. Moreover, high UL111A expression was also associated with increased CD4+ , CD8+ T-lymphocyte and Foxp3+ T-cell infiltration. In vitro assays further demonstrated that LAcmvIL-10 and cmvIL-10 overexpression inhibits GC cell line proliferation, colony formation, migration, and invasion. Conclusions High UL111A expression changes the number of infiltrating T cells and is associated with favorable survival. Therefore, UL111A could be used as an independent prognostic biomarker and might be a potential therapeutic target for GC.

Published
2020

6. Patients with Helicobacter pylori‑positive gastric cancer with human cytomegalovirus infection have a low tendency of advanced lymphatic metastasis in a Chinese population

Author

Wangkai Xie, Chenchen Mao, Zheng Han, Chao Chen, Xiangyang Xue, Xiangwei Sun, Terry Kwok, Xian Shen, Teming Zhang, Sian Chen, and Lei Zhang

Subjects
0301 basic medicine, Human cytomegalovirus, Cancer Research, Oncogene, biology, business.industry, viruses, Cancer, Helicobacter pylori, Cell cycle, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Molecular medicine, Metastasis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Immunology, medicine, Risk factor, business
Abstract

Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV-/H. pylori -, neither HCMV+/H. pylori - nor HCMV+/H. pylori + were associated with metastasis, but HCMV-/H. pylori + co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation.

Published
2021

7. Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer

Author

Wangkai Xie, Yuanbo Hu, Xian Shen, Xiaodong Chen, Xiangyang Xue, Dong Xing, Zhiguang Zhao, Sian Chen, Kezhi Lin, Xiangwei Sun, Chenbin Chen, Jianfeng Xu, and Zheng Han

Subjects
Male, 0301 basic medicine, Cancer Research, Ubiquitin-Protein Ligases, Immunology, medicine.disease_cause, Models, Biological, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Death-associated protein 6, Downregulation and upregulation, Cell Movement, Stomach Neoplasms, Cell Line, Tumor, medicine, Humans, Neoplasm Invasiveness, lcsh:QH573-671, Cell Proliferation, Cell Nucleus, biology, lcsh:Cytology, Cell growth, Chemistry, GTPase-Activating Proteins, Sumoylation, Cell Biology, Middle Aged, Subcellular localization, Cell biology, Ubiquitin ligase, Nuclear Pore Complex Proteins, 030104 developmental biology, Cytoplasm, 030220 oncology & carcinogenesis, Small Ubiquitin-Related Modifier Proteins, biology.protein, Female, RANBP2, Gastric cancer, Carcinogenesis, Co-Repressor Proteins, Molecular Chaperones, Protein Binding, Subcellular Fractions
Abstract

Death domain-associated protein (DAXX) is a complex biological multifunctional protein and is involved in the tumorigenesis and progression of multiple cancers. The accumulation of DAXX in the nucleus is a common phenomenon in tumor cells. However, altering the subcellular localizations of DAXX results in different biological functions, and we also found that its nuclear/cytoplasmic ratio (NCR) was associated with poor prognosis in gastric cancer (GC). In this study, we investigated the effect of cytoplasmic and nuclear DAXX (cDAXX and nDAXX) in GC and the underlying mechanisms. Immunohistochemical detection performed in 323 GC tissues reveled that cDAXX was associated with a better survival, while high nDAXX expression suggested a poorer prognosis outcome. Upregulation of DAXX in the cytoplasm inhibited cell proliferation and promoted apoptosis, whereas downregulation of DAXX in the nucleus displayed opposite effects. Moreover, Transwell assays revealed that DAXX enhanced GC cell migration and invasion. Analysis from the Gene Expression Profile Interactive Analysis (GEPIA) database showed that the expression of DAXX was significantly associated with SUMO-2/3 in GC tissues. Co-immunoprecipitation combined with immunofluorescence analysis indicated that DAXX interacted directly with SUMO-2/3. Subsequently, down-regulating the expression of SUMO-2/3 resulted in altered subcellular localization of DAXX. Bioinformatics analysis showed that RanBP2 may act as SUMO E3 ligase to promote nuclear-plasma transport via combining with RanGAP1. Taken together, our results indicated that DAXX plays opposing roles in GC and suggest a new model whereby cDAXX, nDAXX, and SUMO-2/3 form a molecular network that regulates the subcellular localization of DAXX and thereby modulates its opposing biological effects. Thus, our findings provide a foundation for future studies of DAXX as a novel therapeutic target for patients with GC.

Published
2020

8. CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly

Author

Wangkai Xie, Chao Chen, Mingdong Lu, Xiangyang Xue, Zheng Han, Xian Shen, Teming Zhang, Xin Liu, Chenbin Chen, Sian Chen, Hongjun Chen, and Jingjing Huang

Subjects
0301 basic medicine, Male, Cancer Research, Cell, CD2AP, Biology, Immunofluorescence, migration, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Cell Movement, Stomach Neoplasms, Cell Line, Tumor, medicine, Biomarkers, Tumor, Cell Adhesion, Humans, Neoplasm Metastasis, Cytoskeleton, Cell adhesion, Molecular Biology, Research Articles, Adaptor Proteins, Signal Transducing, medicine.diagnostic_test, Gene Expression Profiling, gastric cancer, Cancer, cytoskeleton, Adhesion, Middle Aged, medicine.disease, invasion, Gene Expression Regulation, Neoplastic, intercellular adhesion, Cytoskeletal Proteins, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Female, RNA Interference, Research Article
Abstract

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2‐associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F‐actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.

Published
2019

9. Patients with

Author

Chao, Chen, Sian, Chen, Zheng, Han, Wangkai, Xie, Teming, Zhang, Chenchen, Mao, Liang, Zhang, Xiangwei, Sun, Terry, Kwok, Xian, Shen, and Xiangyang, Xue

Subjects
co-infection, Helicobacter pylori, human cytomegalovirus, viruses, gastric cancer, Articles, lymphatic metastasis, bacterial infections and mycoses
Abstract

Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV−/H. pylori−, neither HCMV+/H. pylori− nor HCMV+/H. pylori+ were associated with metastasis, but HCMV−/H. pylori+ co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation.

Published
2019

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