Genetic alteration of histone lysine methyltransferases and their significance in renal cell carcinoma

Yan, Libin; Zhang, Yangjun; Ding, Beichen; Zhou, Hui; Yao, Weimin; Xu, Huaxi

doi:10.7717/peerj.6396

“…The heterogeneity of the study populations may have at least partly contributed to this discordance. However, our study indicated that high levels of NSD3 expression indicated poor prognosis for patients with PAAD, KIRP, and UVM, which is consistent with previous studies (32,36,37). A recent study concluded that ablation of NSD3 in a mouse model of LUSC attenuates tumor growth and results in prolonged survival (16).…”

Section: Discussionsupporting

confidence: 91%

Prognostic and Immunological Characterization of NSD3 Evaluated through an Integrative Pan-Cancer Analysis

Li

¹

,

Liu

²

,

Yao

³

et al. 2021

Preprint

0

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Background: Nuclear receptor binding SET domain protein-3 (NSD3) has been reported to be a crucial regulator of carcinogenesis as a histone lysine methyltransferase in multiple cancer types. However, the underlying mechanisms have not been clearly delineated. Therefore, we aimed to investigate the expression pattern, prognostic value, and potential function of NSD3 in 33 types of human cancer. Methods: The potential roles of NSD3 were explored using datasets from The Cancer Genome Atlas (TCGA) pan-cancer dataset and an array of bioinformatics methods, including analyses of the relationship between NSD3 expression and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA amplification, and immune cell inﬁltration across 33 cancer types. Results: Many types of cancers are characterized according to the dysregulation of NSD3, which is associated with the pathological stage of cancer. Patients in our study with higher NDS3 levels, which were attributed to NSD3 copy number amplification, always experienced shorter survival periods. Additionally, NSD3 expression was associated with TMB and MSI in 10 different cancer types. The top five cancers whose NSD3 expression correlated with immune scores were further analyzed. The levels of immune-cell infiltration differed significantly between high and low NSD3-expressing samples in each of the five cancer types. Functional enrichment of the NSD3 co-expressed genes indicated a role for NSD3 in the regulation of immune responses and tumorigenesis. Conclusions: Our study revealed that NSD3 can function as a prognostic marker in various cancers due to its role in tumorigenesis and tumor immunity.

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“…The heterogeneity of the study populations may have at least partly contributed to this discordance. However, our study indicated that high levels of NSD3 expression indicated poor prognosis for patients with PAAD, KIRP, and UVM, which is consistent with previous studies (32,36,37). A recent study concluded that ablation of NSD3 in a mouse model of LUSC attenuates tumor growth and results in prolonged survival (16).…”

Section: Discussionsupporting

confidence: 91%

Prognostic and Immunological Characterization of NSD3 Evaluated Through an Integrative Pan-Cancer Analysis

Li

¹

,

Liu

²

,

Yao

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Background: Nuclear receptor binding SET domain protein-3 (NSD3) has been reported to be a crucial regulator of carcinogenesis as a histone lysine methyltransferase in multiple cancer types. However, the underlying mechanisms have not been clearly delineated. Therefore, we aimed to investigate the expression pattern, prognostic value, and potential function of NSD3 in 33 types of human cancer. Methods: The potential roles of NSD3 were explored using datasets from The Cancer Genome Atlas (TCGA) pan-cancer dataset and an array of bioinformatics methods, including analyses of the relationship between NSD3 expression and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA amplification, and immune cell inﬁltration across 33 cancer types. Results: Many types of cancers are characterized according to the dysregulation of NSD3, which is associated with the pathological stage of cancer. Patients in our study with higher NDS3 levels, which were attributed to NSD3 copy number amplification, always experienced shorter survival periods. Additionally, NSD3 expression was associated with TMB and MSI in 10 different cancer types. The top five cancers whose NSD3 expression correlated with immune scores were further analyzed. The levels of immune-cell infiltration differed significantly between high and low NSD3-expressing samples in each of the five cancer types. Functional enrichment of the NSD3 co-expressed genes indicated a role for NSD3 in the regulation of immune responses and tumorigenesis. Conclusions: Our study revealed that NSD3 can function as a prognostic marker in various cancers due to its role in tumorigenesis and tumor immunity.

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“…However, surgery is not suitable for metastatic RCC, and RCC is insensitive to both chemotherapy and radiotherapy ( Sun et al, 2020 ). Meanwhile, targeted therapies have obviously improved the prognosis of metastatic RCC patients ( Yan et al, 2019 ). Thus, it is essential to explore effective predictive biomarkers for RCC patient prognosis and targeted therapy of RCC.…”

Section: Introductionmentioning

confidence: 99%

Transcription Factors BARX1 and DLX4 Contribute to Progression of Clear Cell Renal Cell Carcinoma via Promoting Proliferation and Epithelial–Mesenchymal Transition

Sun

¹

,

Ge

²

,

Zhang

³

et al. 2021

Front. Mol. Biosci.

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Dysregulation of transcription factors contributes to the carcinogenesis and progression of cancers. However, their roles in clear cell renal cell carcinoma remain largely unknown. This study aimed to evaluate the clinical significance of TFs and investigate their potential molecular mechanisms in ccRCC. Data were accessed from the cancer genome atlas kidney clear cell carcinoma cohort. Bioinformatics algorithm was used in copy number alterations mutations, and differentially expressed TFs’ analysis. Univariate and multivariate Cox regression analyses were performed to identify clinically significant TFs and construct a six-TF prognostic panel. TFs’ expression was validated in human tissues. Gene set enrichment analysis (GSEA) was utilized to find enriched cancer hallmark pathways. Functional experiments were conducted to verify the cancer-promoting effect of BARX homeobox 1 (BARX1) and distal-less homeobox 4 (DLX4) in ccRCC, and Western blot was performed to explore their downstream pathways. As for results, many CNAs and mutations were identified in transcription factor genes. TFs were differentially expressed in ccRCC. An applicable predictive panel of six-TF genes was constructed to predict the overall survival for ccRCC patients, and its diagnostic efficiency was evaluated by the area under the curve (AUC). BARX1 and DLX4 were associated with poor prognosis, and they could promote the proliferation and migration of ccRCC. In conclusion, the six-TF panel can be used as a prognostic biomarker for ccRCC patients. BARX1 and DLX4 play oncogenic roles in ccRCC via promoting proliferation and epithelial–mesenchymal transition. They have the potential to be novel therapeutic targets for ccRCC.

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Genetic alteration of histone lysine methyltransferases and their significance in renal cell carcinoma

Cited by 17 publications

References 41 publications

Prognostic and Immunological Characterization of NSD3 Evaluated through an Integrative Pan-Cancer Analysis

Prognostic and Immunological Characterization of NSD3 Evaluated through an Integrative Pan-Cancer Analysis

Prognostic and Immunological Characterization of NSD3 Evaluated Through an Integrative Pan-Cancer Analysis

Transcription Factors BARX1 and DLX4 Contribute to Progression of Clear Cell Renal Cell Carcinoma via Promoting Proliferation and Epithelial–Mesenchymal Transition

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