Yi‐Wu Dang

First Affiliated Hospital of GuangXi Medical University

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Gang Chen

First Affiliated Hospital of GuangXi Medical University

107

Rong‐Quan He

First Affiliated Hospital of GuangXi Medical University

Zhi‐Guang Huang

First Affiliated Hospital of GuangXi Medical University

Zhen‐Bo Feng

Guangxi Medical University

Dandan Xiong

Guangxi Medical University

Jian‐Di Li

First Affiliated Hospital of GuangXi Medical University

Huayu Wu

Third Affiliated Hospital of Sun Yat-sen University

Gang Chen

First Affiliated Hospital of GuangXi Medical University

Dianzhong Luo

Chinese PLA General Hospital

Peng Lin

Fujian Medical University

Cooperative Institutions

Guangxi Medical University

320

First Affiliated Hospital of GuangXi Medical University

269

Sun Yat-sen University

Sichuan University

Chinese Academy of Sciences

Capital Medical University

Chinese Academy of Medical Sciences & Peking Union Medical College

Central South University

Shanghai Jiao Tong University

Fudan University

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Prognostic alternative splicing signatures and underlying regulatory network in esophageal carcinoma.

PubMed (2019)

Zucheng Xie Huayu Wu Fu‐Chao Ma Yi‐Wu Dang Zhigang Peng

Alternative splicing (AS) has been widely reported to play an important role in cancers, including esophageal carcinoma (ESCA). However, no study has comprehensively investigated the clinical use of combination of prognostic AS events and clinicopathological parameters. Therefore, we collected 165 ESCA patients including 83 esophageal adenocarcinoma (EAC) and 82 esophageal squamous cell carcinoma (ESCC) patients from The Cancer Genome Atlas to explore the survival rate associated with seven types of AS events. Prognostic predictors for the clinical outcomes of ESCA patients were built. Predictive prognosis models of the alternative acceptor site in ESCA (area under the curve [AUC] = 0.83), alternative donor site in EAC (AUC = 0.99), and alternative terminator site in ESCC (AUC = 0.974) showed the best predictive efficacy. A novel combined prognostic model of AS events and clinicopathological parameters in ESCA was also constructed. Combined prognostic models of ESCA all showed better predictive efficacy than independent AS models or clinicopathological parameters model. Through constructing splicing regulatory network, the expression of AS factor was found to be negatively correlated with the most favorable AS events. Moreover, gene amplification, mutation, and copy number variation of AS genes were commonly observed, which may indicate the molecular mechanism of how the AS events influence survival. Conclusively, the constructed prognostic models based on AS events, especially the combined prognostic models of AS signatures and clinicopathological parameters could be used to predict the outcome of ESCA patients. Moreover, the splicing regulatory network and genomic alteration in ESCA could be used for illuminating the potential molecular mechanism.

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Downregulation of zinc finger protein 71 in laryngeal squamous cell carcinoma tissues and its potential molecular mechanism and clinical significance: a study based on immunohistochemistry staining and data mining

World Journal of Surgical Oncology (2022)

Fang‐Cheng Jiang Jia‐Yuan Luo Yi‐Wu Dang Huiping Lu Dongming Li

Abstract Background The molecular mechanism of laryngeal squamous cell carcinoma (LSCC) is not completely clear, which leads to poor prognosis and treatment difficulties for LSCC patients. To date, no study has reported the exact expression level of zinc finger protein 71 (ZNF71) and its molecular mechanism in LSCC. Methods In-house immunohistochemistry (IHC) staining (33 LSCC samples and 29 non-LSCC samples) was utilized in analyzing the protein expression level of ZNF71 in LSCC. Gene chips and high-throughput sequencing data collected from multiple public resources (313 LSCC samples and 192 non-LSCC samples) were utilized in analyzing the exact mRNA expression level of ZNF71 in LSCC. Single-cell RNA sequencing (scRNA-seq) data was used to explore the expression status of ZNF71 in different LSCC subpopulations. Enrichment analysis of ZNF71, its positively and differentially co-expressed genes (PDCEGs), and its downstream target genes was employed to detect the potential molecular mechanism of ZNF71 in LSCC. Moreover, we conducted correlation analysis between ZNF71 expression and immune infiltration. Results ZNF71 was downregulated at the protein level (area under the curve [AUC] = 0.93, p < 0.0001) and the mRNA level (AUC = 0.71, p = 0.023) in LSCC tissues. Patients with nodal metastasis had lower protein expression level of ZNF71 than patients without nodal metastasis ( p < 0.05), and male LSCC patients had lower mRNA expression level of ZNF71 than female LSCC patients ( p < 0.01). ZNF71 was absent in different LSCC subpopulations, including cancer cells, plasma cells, and tumor-infiltrated immune cells, based on scRNA-seq analysis. Enrichment analysis showed that ZNF71 and its PDCEGs may influence the progression of LSCC by regulating downstream target genes of ZNF71. These downstream target genes of ZNF71 were mainly enriched in tight junctions. Moreover, downregulation of ZNF71 may influence the development and even therapy of LSCC by reducing immune infiltration. Conclusion Downregulation of ZNF71 may promote the progression of LSCC by reducing tight junctions and immune infiltration; this requires further study.

Surgical oncology

Clinical Significance

10.1186/s12957-022-02823-8

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Clinical Significance of the Interleukin 24 mRNA Level in Head and Neck Squamous Cell Carcinoma and Its Subgroups: An In Silico Investigation

Journal of Oncology (2020)

Lanlan Qiu Xiao-Guohui Zhang Gang Chen Yi‐Wu Dang Zhi‐Guang Huang

IL24 mRNA is known to have an apoptotic effect on cancer cells but not on noncancer cells. However, the expression level of the IL24 mRNA in head and neck squamous cell carcinoma (HNSCC) and its subgroups is rarely studied. In this study, the clinical implication of IL24 mRNA was evaluated in the common subgroups of HNSCC, including oral squamous cell carcinoma (OSCC), nasopharyngeal carcinoma (NPC), and laryngeal squamous cell carcinoma (LSCC) for analysis. Substantial IL24 mRNA expression data were calculated from several databases, such as the Gene Expression Omnibus (GEO), ArrayExpress, Sequence Read Archive (SRA), ONCOMINE, and The Cancer Genome Atlas (TCGA) databases. We ultimately collected a total of 41 microarrays and RNA-seq including 1,564 HNSCC and 603 noncancer tissue samples. IL24 mRNA was highly expressed in OSCC, LSCC, and NPC as shown by the separated standard mean difference (SMD), as well as HNSCC as a whole part (SMD = 1.47, 95% confdence interval (CI) = 1.24−1.70, P<0.0001). In all subgroups, the IL24 mRNA upregulation had the ability to distinguish cancer from noncancer tissue with area under the curves (AUCs) of the summary receiver operating characteristic (sROC) higher than 0.85. In conclusion, IL24 mRNA may be used as a potential marker for cancer screening, and its clinical diagnostic value needs to be further studied. It also provides a new idea for the treatment of the IL24 gene in HNSCC and its subgroups in the future.

Clinical Significance

10.1155/2020/7042025

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Integrative analysis of BSG expression in NPC through immunohistochemistry and public high-throughput gene expression data.

PubMed (2017)

Li Gao Jin‐Cai Zhong Wenting Huang Yi‐Wu Dang Min Kang

Though basigin (BSG) was reported to be overexpressed in nasopharyngeal carcinoma (NPC) and correlate with the development of NPC, the molecular basis of BSG in NPC remained elusive. The aim of the research was to investigate BSG expression in NPC and the potential molecular mechanism underlying it.BSG expression in NPC tissues was detected with immunohistochemistry. Chi-square test, Kruskal-Wallis test and Spearman correlation test were performed to examine the relationship between BSG expression and the clinico-pathological features as well as EGFR and P-53 expression in NPC. In addition, data from the Human Protein Atlas (HPA) database and oncomine were collected to validate BSG expression in NPC. Meta-analysis was conducted to investigate the association between BSG expression and the clinico-pathological variables of NPC. The prognostic value and the alteration of BSG gene status were also analyzed with data from The Cancer Genome Atlas (TCGA).BSG presented notably higher expression in NPC tissues than in non-cancer tissues. Moreover, IHC results showed that BSG expression was significantly correlated with tumor progression. A positive correlation was also found between BSG expression and EGFR, P53 expression. Meta-analysis confirmed that BSG was indicative of lymph node metastasis and TNM stage in NPC. Additionally, data from cBioPortal indicated that alteration of BSG gene existed in 5% of NPC cases and BSG correlative genes were obtained from the Co-expression Analysis in TCGA.BSG was overexpressed in NPC and might have an oncogenic effect on the tumorigenesis and progression of NPC.

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Prognostic index of aberrant mRNA splicing profiling acts as a predictive indicator for hepatocellular carcinoma based on TCGA SpliceSeq data

International Journal of Oncology (2019)

Huayu Wu Zhigang Peng Rong‐Quan He Bin Luo Jie Ma

Alternative splicing in tumor cells may be used as a molecular marker for the differential diagnosis of certain tumor types and assessment of prognosis. The aim of the present study was to investigate the associations among alternative splicing events, splicing factors, and the survival of patients with hepatocellular carcinoma (HCC). The alternative splicing event profiles of 371 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) SpliceSeq data, and the percent‑splice‑in value for each splicing event was calculated. The association between alternative splicing events and overall survival was evaluated. The most significant prognosis‑related splicing events were used to build up a prognostic index (PI). A total of 3,082 survival‑associated alternative splicing events were detected in HCC. The final PI based on all of the most significant candidate alternative splicing events exhibited better performance in distinguishing good or poor survival in patients compared to the PI based on a single type of splicing event. Receiver operating characteristic curves confirmed the high efficiency of the PI in predicting the survival of HCC patients, with an area under the curve of 0.914. The overexpression of 32 prognosis‑related splicing factor genes could also predict poor prognosis in patients with HCC. In conclusion, the constructed computational prognostic model based on HCC‑specific alternative splicing events may be used as a molecular marker for the prognosis of HCC.

Splicing factor

10.3892/ijo.2019.4834

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Potential Targets of Nitidine Chloride in Wilms Tumour Revealed by Network Pharmacology, RNA-Seq and Microarrays

SSRN Electronic Journal (2021)

Li Gao Dandan Xiong Qiong-Qian Xu Peng Chen Yong Li

Background: Wilms tumour is the most common childhood renal cancer that requires development of better treatments. Nitidine chloride, a Chinese traditional medicine, could have therapeutic potential for Wilms tumour, however there have been no studies to date. Methods: In-house RNA-seq was performed and public RNA-seq plus microarrays datasets were incorporated for identifying the landscape of differentially expressed genes (DEGs) in Wilms tumour. Meanwhile, the potential targets of nitidine chloride in Wilms tumour were acquired through combined analysis of computational prediction and DEG, which was further validated by molecular docking. The molecular mechanism of nitidine chloride-putative targets was investigated through transcription factors and gene set enrichment analysis. Findings: As a result, a total of 1819 upregulated DEGs and 1942 downregulated DEGs were identified in Wilms tumour. Twenty-three putative targets of nitidine chloride in Wilms tumour were determined and nine showed strong binding force with nitidine chloride in molecular docking. IMPDH2 and MAP4K4 exhibited significant value of prognostic signification. The upregulation of these putative targets in Wilms tumour may be induced by transcription factors (TFs) such as MYC, E2F1, SOX2, MYCN, MITF and CREM. The hub putative targets of nitidine chloride in Wilms tumour were enriched in pathways such as cell cycle, chemokine signaling pathway, glycolysis and gluconeogenesis. Interpretation: In conclusion, the putative pharmacologic targets and molecular pathways of nitidine chloride in Wilms tumour were unveiled in this study. Further research is necessary for confirming the therapeutic effect of nitidine chloride in Wilms tumour. Funding: This work was supported by Natural Science Foundation of Guangxi, China (2018GXNSFAA294025); Guangxi Medical High-level Key Talents Training "139" Program (2020); Guangxi Medical University Training Program for Distinguished Young Scholars ; Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University; Guangxi Degree and Postgraduate Education Reform and Development Research Projects, China (JGY2019050); Innovation Project of Guangxi Graduate Education; Guangxi Zhuang Autonomous Region Health and Family Planning Commission Self-financed Scientific Research Project (Z20200317); Innovation Project of Guangxi Graduate Education (YCSW2021121Declaration of Interests: The authors have declared no competing interests.Ethics Approval Statement: All patients provided informed consent and approval of this research project was granted by the medical ethics committee of the First Affiliated Hospital of Guangxi Medical University (2020-ky-guoji-135).All experiments involving animals were conducted according to the ethical policies and procedures approved by the ethics committee of the First Affiliated Hospital of Guangxi Medical Univeristy (Approval no. 2020-ky-guoji-135).

Wilms tumour

10.2139/ssrn.3917047

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Downregulation of zinc finger protein 71 expression in oral squamous cell carcinoma tissues and its underlying molecular mechanism

Pathology - Research and Practice (2022)

Fang‐Cheng Jiang Guosheng Li Jia‐Yuan Luo Zhi‐Guang Huang Yi‐Wu Dang

Pathogenesis

10.1016/j.prp.2022.154109

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Citations (1)

A circRNA–miRNA–mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma

Journal of Translational Medicine (2018)

Dandan Xiong Yi‐Wu Dang Peng Lin Dong‐yue Wen Rong‐Quan He

Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC). A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC. Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA–miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein–protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis. Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA–miRNA–mRNA network view.

KEGG

Circular RNA

10.1186/s12967-018-1593-5

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Citations (251)

OSacc: Gene Expression-Based Survival Analysis Web Tool For Adrenocortical Carcinoma

DOAJ (DOAJ: Directory of Open Access Journals) (2019)

Li Xie Qingyu Wang Nan F Long Ge Yi‐Wu Dang

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Integrated assessment of CDK1 upregulation in thyroid cancer.

PubMed (2019)

Haiping Zheng Zhi‐Guang Huang Rong‐Quan He Huiping Lu Yi‐Wu Dang

Cyclin-dependent kinase 1 (CDK1) has a unique role in cell cycle regulation, as it is crucial for cell cycle progression and cell division. The aim of the present study was to use a combination of various detection methods to examine the expression and clinical significance of CDK1 in thyroid cancer (THCA). We used in-house tissue microarrays, immunohistochemistry, public RNA-sequencing, gene microarrays, and meta-analyses to conduct a comprehensive analysis of the role of CDK1 in the occurrence and development of THCA. CDK1 protein expression was notably higher in THCA tissues than in non-cancer tissues as evidenced by the in-house tissue microarrays. The expression of CDK1 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples. The pooled standardized mean difference (SMD) for CDK1 was 0.71 (95% CI, 0.46-0.95) including a total of 931 THCA and 585 non-cancerous thyroid tissue samples. An aggregation of the immunohistochemistry results and the RNA-sequencing/microarray findings gave a pooled SMD for CDK1 expression of 2.13 (95% CI, 1.30-2.96). The final area under curve (AUC) for the summarized receiver operating characteristic (sROC) was 0.7941 using all 1102 cases of THCA and 672 cases of controls. KEGG analysis with the co-expressed genes of CDK1 in THCA demonstrated the top enriched pathways to be the cell cycle, thyroid hormone synthesis, autoimmune thyroid disease, etc. In summary, we reveal the overexpression of CDK1 in THCA based on multiple detection methods that combine independent cohorts. However, further studies are required to elucidate the molecular mechanisms of CDK1 that promotes the biological aggressiveness of THCA cells.

Tissue microarray

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Citations (21)