Comprehensive analysis of transcriptome data stemness indices identifies key genes for controlling cancer stem cell characteristics in gastric cancer

Xia, Xinxin; Li, Yuejun

doi:10.21037/tcr-20-704

Cited by 17 publications

(12 citation statements)

References 54 publications

(59 reference statements)

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“…We classified BC into PAM50-based intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like subtype ( Wang et al, 2021 ). Further, the expression data of FLT3 in different phenotypes were analyzed and visualized using ggplot2 ( Gustavsson et al, 2022 ) and ggpubr ( Xia and Li, 2020 ) R packages. Meanwhile, DNA methylation analysis of FLT3 was conducted along with data on clinical features and vital status.…”

Section: Methodsmentioning

confidence: 99%

High FLT3 expression indicates favorable prognosis and correlates with clinicopathological parameters and immune infiltration in breast cancer

Chen

Wang

et al. 2022

Front. Genet.

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Purpose: Breast cancer is a highly heterogeneous malignancy, seriously threatening female health worldwide and inducing higher mortalities. Few have the studies evaluated Fms-like TyrosineKinase-3 (FLT3) in prognostic risk, immunotherapy or any other treatment of breast cancer. Our study focused on investigating the function of FLT3 in breast cancer.Patients and methods: Based on transcriptome and methylation data mined from The Cancer Gene Atlas (TCGA), we explored the clinical features of FLT3 expression in 1079 breast cancer samples. RT-qPCR in cell lines and tissue samples was used to verify the expression difference of FLT3. Kaplan–Meier survival analysis and cox regression models were employed for screening of FLT3 with potential prognostic capacity. Subsequently, functional analysis of the co-expressed genes was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analysis (GSEA). The correlation between FLT3 expression and tumor immune infiltration was jointly analyzed with estimate, ssGSEA, TIMER, and TISIDB. Then we employed checkpoint-related molecules, immunophenoscore (IPS), and tumor mutation burden (TMB) to assess the efficacy of immuno-checkpoint inhibitors (ICIs). Pearson correlation coefficient was employed to exam the association between DNA methylation and FLT3 expression.Results: FLT3 displays an elevated expression in breast cancer than normal pairs and is significantly associated with multiple clinical characteristics like age, menopause status, histological type, pathological stage, and molecular subtype as well as increased overall survival (OS). Additionally, FLT3 is a favorable independent prognostic factor. GO, KEGG, and GSEA suggested that FLT3 was associated with diversified immune-related features. FLT3 expression is correlated with the abundance of various immune cells namely CD4+T cell, CD8+ T cell, myeloid dendritic cell, and neutrophil as well as immune inhibitors especially CTLA4, which is positively correlated with FLT3 expression. Moreover, TMB displayed a negative correlation with FLT3 expression while IPS showed adverse tendency. Ultimately, the methylation of FLT3 downregulates the gene expression and closely binds to a few clinical parameters.Conclusion: FLT3 can be used for prognostic prediction and is relevant to immune infiltration in breast cancer. FLT3 may pave the way for future novel immunotherapies.

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Section: Methodsmentioning

confidence: 99%

High FLT3 expression indicates favorable prognosis and correlates with clinicopathological parameters and immune infiltration in breast cancer

Chen

Wang

et al. 2022

Front. Genet.

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“…To investigate the correlation between immune cell infiltration and risk scores in THCA patients, we performed Spearman correlation analysis between risk scores and immune cell infiltration [34] using the R package scales ggplot2, ggtext, tidyverse, and ggpubr. [35][36][37] If the P-value of the correlation test was less than .05, we drew scatter plots and a bubble plot of the correlation between immune cell infiltration and patient risk score for visualization. [38] 3.…”

Section: Correlation Analysis Of Immune Cells and Risk Scores In Thca...mentioning

confidence: 99%

Construction and validation of a novel prognostic model for thyroid cancer based on N7-methylguanosine modification-related lncRNAs

et al. 2022

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Background: To construct and verify a novel prognostic model for thyroid cancer (THCA) based on N7-methylguanosine modification-related lncRNAs (m7G-lncRNAs) and their association with immune cell infiltration. Methods: In this study, we identified m7G-lncRNAs using co-expression analysis and performed differential expression analysis of m7G-lncRNAs between groups. We then constructed a THCA prognostic model, performed survival analysis and risk assessment for the THCA prognostic model, and performed independent prognostic analysis and receiver operating characteristic curve analyses to evaluate and validate the prognostic value of the model. Furthermore, analysis of the regulatory relationship between prognostic differentially expressed m7G-related lncRNAs (PDEm7G-lncRNAs) and mRNAs and correlation analysis of immune cells and risk scores in THCA patients were carried out. Results: We identified 29 N7-methylguanosine modification-related mRNAs and 116 differentially expressed m7G-related lncRNAs, including 87 downregulated and 29 upregulated lncRNAs. Next, we obtained 8 PDEm7G-lncRNAs. A final optimized model was constructed consisting of 5 PDEm7G-lncRNAs (DOCK9−DT, DPP4–DT, TMEM105, SMG7–AS1 and HMGA2–AS1). Six PDEm7G-lncRNAs (DOCK9–DT, DPP4–DT, HMGA2–AS1, LINC01976, MID1IP1–AS1, and SMG7–AS1) had positive regulatory relationships with 10 PDEm7G-mRNAs, while 2 PDEm7G-lncRNAs (LINC02026 and TMEM105) had negative regulatory relationships with 2 PDEm7G-mRNAs. Survival curves and risk assessment predicted the prognostic risk in both groups of patients with THCA. Forest maps and receiver operating characteristic curves were used to evaluate and validate the prognostic value of the model. Finally, we demonstrated a correlation between different immune cells and risk scores. Conclusion: Our results will help identify high-risk or low-risk patients with THCA and facilitate early prediction and clinical intervention in patients with high risk and poor prognosis.

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“…In the present study, the findings confirmed that NCAPG was highly expressed in LUAD tissues and cells. Previously, transcriptome analysis identified NCAPG as a possible key gene implicated in cancer cell stemness 18,19 . NCAPG was positively correlated with the stemness index as presented by bioinformatics analysis.…”

Section: Discussionmentioning

confidence: 94%

NCAPG stimulates lung adenocarcinoma cell stemness through aerobic glycolysis

Zhang

Liu

et al. 2023

Clinical Respiratory J

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BackgroundCancer stem cells are pivotal in cancer progression and therapy, including lung adenocarcinoma (LUAD). High NCAPG level is implicated in malignant tumorigenesis, but investigations on NCAPG and LUAD stem cells are warranted. Hence, projecting the impact of NCAPG on cell stemness and the targeted therapy for LUAD is of the essence.MethodsBioinformatics analyzed NCAPG expression in LUAD tissues. qRT‐PCR assayed NCAPG expression in LUAD cells. CCK‐8 assessed cell viability and cell sphere‐forming assay measured sphere‐forming ability. Western blot assessed expression of stem cell‐related markers (CD133, CD44, Oct‐4) and specific genes (HK2, PKM2, LDHA) related to glycolysis metabolism pathway. Cellular glycolytic capacity was assayed by glycolytic metabolites pyruvic acid, lactate, citrate, and malate assay kits, and extracellular acidification rate and oxygen consumption rate analyzers.ResultsNCAPG was upregulated in LUAD and enriched in the aerobic glycolysis pathway, and its expression was positively correlated with that of glycolytic marker genes. Cell function assays revealed that NCAPG stimulated proliferation, stemness, and glycolytic activity of LUAD cells. Rescue experiments unveiled that 2‐DG (glycolysis inhibitor) was able to reverse the stimulative impact of NCAPG overexpression on proliferation, stemness, and glycolytic activity of LUAD cells.ConclusionNCAPG stimulated LUAD cell stemness through activation of glycolysis pathway. NCAPG may be possible biomarker for diagnosis and target for treatment of LUAD.

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Comprehensive analysis of transcriptome data stemness indices identifies key genes for controlling cancer stem cell characteristics in gastric cancer

Cited by 17 publications

References 54 publications

High FLT3 expression indicates favorable prognosis and correlates with clinicopathological parameters and immune infiltration in breast cancer

High FLT3 expression indicates favorable prognosis and correlates with clinicopathological parameters and immune infiltration in breast cancer

Construction and validation of a novel prognostic model for thyroid cancer based on N7-methylguanosine modification-related lncRNAs

NCAPG stimulates lung adenocarcinoma cell stemness through aerobic glycolysis

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