Cancer-associated fibroblasts and the related Runt-related transcription factor 2 (RUNX2) promote bladder cancer progression

Liu, Bitian; Shen, Pan; Liu, Junlong; Kong, Chuize

doi:10.1016/j.gene.2021.145451

Cited by 24 publications

(21 citation statements)

References 27 publications

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“…Runt-related transcription factor 2 ( RUNX2 ) is a key factor of osteoblast differentiation and has been reported to be associated with epithelial-mesenchymal transition in bladder tumors. Furthermore, RUNX2 could predict early recurrence in bladder cancer patients with high accuracy [ 47 , 48 ]. Similar to past studies, SSH1 and RUNX2 were associated with the increased risk of tumor recurrence in our study.…”

Section: Discussionmentioning

confidence: 99%

Immune profiles and DNA methylation alterations related with non-muscle-invasive bladder cancer outcomes

et al. 2022

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Background Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC. Methods and results We used the Illumina HumanMethylationEPIC array to measure peripheral blood DNA methylation profiles of NMIBC patients (N = 603) enrolled in a population-based cohort study in New Hampshire and applied cell type deconvolution to estimate immune cell-type proportions. Using Cox proportional hazard models, we identified that increasing CD4T and CD8T cell proportions were associated with a statistically significant decreased hazard of tumor recurrence or death (CD4T: HR = 0.98, 95% CI = 0.97–1.00; CD8T: HR = 0.97, 95% CI = 0.95–1.00), whereas increasing monocyte proportion and methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) were associated with the increased hazard of tumor recurrence or death (monocyte: HR = 1.04, 95% CI = 1.00–1.07; mdNLR: HR = 1.12, 95% CI = 1.04–1.20). Then, using an epigenome-wide association study (EWAS) approach adjusting for age, sex, smoking status, BCG treatment status, and immune cell profiles, we identified 2528 CpGs associated with the hazard of tumor recurrence or death (P < 0.005). Among these CpGs, the 1572 were associated with an increased hazard and were significantly enriched in open sea regions; the 956 remaining CpGs were associated with a decreased hazard and were significantly enriched in enhancer regions and DNase hypersensitive sites. Conclusions Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence.

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Section: Discussionmentioning

confidence: 99%

Immune profiles and DNA methylation alterations related with non-muscle-invasive bladder cancer outcomes

et al. 2022

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“…These findings agree with those of previous studies that reported RUNX2 as being associated with cancer progression. [35,36] TCGA contains data for 33 types of cancer, which can be further divided based on the source of the organ system or histopathologic classification. [37] Pan-squamous cell carcinoma (PSCC) arises from the epithelia of the aerodigestive and genitourinary tracts and includes LUSC, HNSC, ESCA, CESC, and BLCA.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer landscape of the RUNX protein family reveals their potential as carcinogenic biomarkers and the mechanisms underlying their action

Shen

Sun

Liu

et al. 2022

Journal of Translational Internal Medicine

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Background The RUNX family of transcription factors plays an important regulatory role in tumor development. Although the importance of RUNX in certain cancer types is well known, the pan-cancer landscape remains unclear. Materials and Methods Data from The Cancer Genome Atlas (TCGA) provides a pan-cancer overview of the RUNX genes. Hence, herein, we performed a pan-cancer analysis of abnormal RUNX expression and deciphered the potential regulatory mechanism. Specifically, we used TCGA multi-omics data combined with multiple online tools to analyze transcripts, genetic alterations, DNA methylation, clinical prognoses, miRNA networks, and potential target genes. Results RUNX genes are consistently overexpressed in esophageal, gastric, pancreatic, and pan-renal cancers. The total protein expression of RUNX1 in lung adenocarcinoma, kidney renal clear cell carcinoma (KIRC), and uterine corpus endometrial carcinoma (UCEC) is consistent with the mRNA expression results. Moreover, increased phosphorylation on the T14 and T18 residues of RUNX1 may represent potential pathogenic factors. The RUNX genes are significantly associated with survival in pan-renal cancer, brain lower-grade glioma, and uveal melanoma. Meanwhile, various mutations and posttranscriptional changes, including the RUNX1 D96 mutation in invasive breast carcinoma, the co-occurrence of RUNX gene mutations in UCEC, and methylation changes in the RUNX2 promoter in KIRC, may be associated with cancer development. Finally, analysis of epigenetic regulator co-expression, miRNA networks, and target genes revealed the carcinogenicity, abnormal expression, and direct regulation of RUNX genes. Conclusions We successfully analyzed the pan-cancer abnormal expression and prognostic value of RUNX genes, thereby providing potential biomarkers for various cancers. Further, mutations revealed via genetic alteration analysis may serve as a basis for personalized patient therapies.

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“…Our results indicate that the RUNX gene family is associated with levels of immune infiltration, poor prognosis, and drug response in various types of cancer. In addition, these findings highlight the potential use of members of the RUNX gene family as biomarkers for cancer progression and prognosis, and as potential treatment targets in various cancer types [ 36 – 39 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value and immune characteristics of RUNX gene family in human cancers: a pan-cancer analysis

Han

Chen

Shen

et al. 2022

Aging

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Background: Runt-related transcription factors (RUNX) are involved in numerous fundamental biological processes and play crucial parts in tumorigenesis and metastasis both directly and indirectly. However, the pan-cancer evidence of the RUNX gene family is not available. Methods: In this study, we analyzed the potential association between RUNX gene family expression and patient’s prognosis, immune cell infiltration, drug response, and genetic mutation data across different types of tumors using based on The Cancer Genome Atlas, Gene Expression Omnibus, and Oncomine database. Results: The results showed that the expression of the RUNX gene family varied among different cancer types, revealing its heterogeneity in cancers and that expression of RUNX2 was lower than that of RUNX1 and RUNX3 across all cancer types. RUNX gene family gene expression was related to prognosis in several cancers. Furthermore, our study revealed a clear association between RUNX gene family expression and ESTIMATE score, RNA stemness, and DNA stemness scores. Compared with RUNX1 and RUNX2, RUNX3 showed relatively low levels of genetic alterations. RUNX gene family genes had clear associations with immune infiltrate subtypes, and their expression was positively related to immune checkpoint genes and drug sensitivity in most cases. Two immunotherapy cohorts confirm that the expression of RUNX was correlated with the clinical response of immunotherapy. Conclusions: These findings will help to elucidate the potential oncogenic roles of RUNX gene family genes in different types of cancer and it can function as a prognostic marker in various malignant tumors.

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Cancer-associated fibroblasts and the related Runt-related transcription factor 2 (RUNX2) promote bladder cancer progression

Cited by 24 publications

References 27 publications

Immune profiles and DNA methylation alterations related with non-muscle-invasive bladder cancer outcomes

Immune profiles and DNA methylation alterations related with non-muscle-invasive bladder cancer outcomes

Pan-cancer landscape of the RUNX protein family reveals their potential as carcinogenic biomarkers and the mechanisms underlying their action

Prognostic value and immune characteristics of RUNX gene family in human cancers: a pan-cancer analysis

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