The Y-linked proto-oncogene TSPY contributes to poor prognosis of the male hepatocellular carcinoma patients by promoting the pro-oncogenic and suppressing the anti-oncogenic gene expression

Kido, Tatsuo; Lau, Yun‐Fai Chris

doi:10.1186/s13578-019-0287-x

Cited by 21 publications

(32 citation statements)

References 95 publications

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“…HMMR has not been directly reported as therapeutic target for HCC. The Y-linked proto-oncogene could promote the expression of HMMR, which was correlated with poor prognosis in the patients with HCC (Kido & Lau, 2019). Over-expression of HMMR was verified as indicators of poor prognosis and metastasis in lung cancer (Liu et al, 2019;Zhang, Zhang & Yu, 2019).…”

Section: Hazard Ratiomentioning

confidence: 87%

A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma

Zhou

Zhang

Cai

et al. 2020

PeerJ

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Background Hepatocellular carcinoma (HCC) is one of the most universal malignant liver tumors worldwide. However, there were no systematic studies to establish glycolysis‑related gene pairs (GRGPs) signatures for the patients with HCC. Therefore, the study aimed to establish novel GRGPs signatures to better predict the prognosis of HCC. Methods Based on the data from Gene Expression Omnibus, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium databases, glycolysis-related mRNAs were used to construct GRGPs. Cox regression was applied to establish a seventeen GRGPs signature in TCGA dataset, which was verified in two validation (European and American, and Asian) datasets. Results Seventeen prognostic GRGPs (HMMR_PFKFB1, CHST1_GYS2, MERTK_GYS2, GPC1_GYS2, LDHA_GOT2, IDUA_GNPDA1, IDUA_ME2, IDUA_G6PD, IDUA_GPC1, MPI_GPC1, SDC2_LDHA, PRPS1_PLOD2, GALK1_IER3, MET_PLOD2, GUSB_IGFBP3, IL13RA1_IGFBP3 and CYB5A_IGFBP3) were identified to be significantly progressive factors for the patients with HCC in the TCGA dataset, which constituted a GRGPs signature. The patients with HCC were classified into low-risk group and high-risk group based on the GRGPs signature. The GRGPs signature was a significantly independent prognostic indicator for the patients with HCC in TCGA (log-rank P = 2.898e−14). Consistent with the TCGA dataset, the patients in low-risk group had a longer OS in two validation datasets (European and American: P = 1.143e−02, and Asian: P = 6.342e−08). Additionally, the GRGPs signature was also validated as a significantly independent prognostic indicator in two validation datasets. Conclusion The seventeen GRGPs and their signature might be molecular biomarkers and therapeutic targets for the patients with HCC.

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Section: Hazard Ratiomentioning

confidence: 87%

A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma

Zhou

Zhang

Cai

et al. 2020

PeerJ

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“…[23]. Kido et al conformed that PPARGC1A was bene cial to the survival of individuals with liver malignancies and had a negative correlation with the expression of the testis speci c protein Y [24]. Zhang et al identi ed elevated expression of IFIT1 as a positive outcome indicator of progression-free survival as well as the period of overall survival in glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

A novel RNA binding protein-associated prognostic model to predict overall survival in hepatocellular carcinoma patients

Liu

Qin

Hai

et al. 2020

Preprint

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Abstract Background Hepatocellular carcinoma (HCC) represents one of the deadliest malignancies worldwide. Despite significant advances in diagnosis and treatment, the mortality rate from HCC persists at a substantial level. This research strives to establish a prognostic model based on the RNA binding proteins (RBPs) that can predict HCC patients’ OS. Methods There was an RNA-seq data set derived from the Cancer Genome Atlas (TCGA) databank which was included in our research as well as a Microarray data set (GSE14520). The differentially expressed RBPs between HCC and normal tissues were investigated in TCGA dataset. Subsequently, the TCGA data set was randomly split into a training and a testing cohort. The prognostic model of the training cohort was developed by applying univariate Cox regression and lasso Cox regression analyses and multivariate Cox regression analysis. In order to evaluate the prognostic value of the model, a comprehensive survival assessment was conducted. Results A total of 133 differentially expressed RBPs were identified. Five RBPs (RPL10L, EZH2, PPARGC1A, ZNF239, IFIT1) were used to construct the model. The model accurately predicted the prognosis of liver cancer patients in both the TCGA cohort and the GSE14520 validation cohort. HCC patients could be assigned into a high-risk group and a low-risk group by this model, and the overall survival of these two groups was significantly different. Furthermore, the risk scores obtained by our model were highly correlated with immune cell infiltration. . Conclusions Five RBPs-related prognostic models were constructed and validated to predict OS reliably in HCC individuals. It helps to identify patients at high risk of mortality with the risk prediction score, which optimizes personalized therapeutic decision-making.

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“…Approximately 20 million sequence reads per sample were mapped onto the Ensembl GRCh37/UCSC hg19 human reference genome using TopHat software 19,31 . Expression levels were calculated using the featureCounts program 42 .…”

Section: Methodsmentioning

confidence: 99%

“…Various studies, including ours, have demonstrated that several Y chromosome genes, such as testis‐specific protein Y‐encoded ( TSPY ), variable charge Y ( VCY ), and RNA‐binding motif Y ( RBMY ), are ectopically expressed in male HCCs at high frequency, 14‐18 thereby potentially exerting male‐specific functions in the oncogenic processes and contributing to sex differences in HCC patients. Indeed, overexpression of the putative Y‐linked gonadoblastoma gene TSPY in HCC cells could promote cell proliferation and upregulate various cell‐cycle regulators, including CDC25B, whose high expression levels are closely correlated with poor prognosis of HCC patients 19 …”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we investigated the expression patterns of RBMY in clinical HCC specimens by immunohistochemistry and explored the immediate effects of RBMY overexpression in a hepatocellular carcinoma cell line HuH‐7 and a hepatoblastoma cell line HepG2 using the tet‐ON conditional gene activation system, 30 and transcriptome 19,31 and pathway analyses 32,33 . In vivo effects of RBMY overexpression were further studied using the constitutively active AKT and RAS oncogene‐induced mouse liver cancer model and the hydrodynamic transfection technique 34‐36 .…”

Section: Introductionmentioning

confidence: 99%

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Potential dual functional roles of the Y‐linked RBMY in hepatocarcinogenesis

et al. 2020

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Hepatocellular carcinoma (HCC) is a highly heterogeneous liver cancer with significant male biases in incidence, disease progression, and outcomes. Previous studies have suggested that genes on the Y chromosome could be expressed and exert various male‐specific functions in the oncogenic processes. In particular, the RNA‐binding motif on the Y chromosome (RBMY) gene is frequently activated in HCC and postulated to promote hepatic oncogenesis in patients and animal models. In the present study, immunohistochemical analyses of HCC specimens and data mining of The Cancer Genome Atlas (TCGA) database revealed that high‐level RBMY expression is associated with poor prognosis and survival of the patients, suggesting that RBMY could possess oncogenic properties in HCC. To examine the immediate effect(s) of the RBMY overexpression in liver cancer cells, cell proliferation was analyzed on HuH‐7 and HepG2 cells. The results unexpectedly showed that RBMY overexpression inhibited cell proliferation in both cell lines as its immediate effect, which led to vast cell death in HuH‐7 cells. Transcriptome analysis showed that genes involved in various cell proliferative pathways, such as the RAS/RAF/MAP and PIP3/AKT signaling pathways, were downregulated by RBMY overexpression in HuH‐7 cells. Furthermore, in vivo analyses in a mouse liver cancer model using hydrodynamic tail vein injection of constitutively active AKT and RAS oncogenes showed that RBMY abolished HCC development. These findings support the notion that Y‐linked RBMY could serve dual tumor‐suppressing and tumor‐promoting functions, depending on the spatiotemporal and magnitude of its expression during oncogenic processes, thereby contributing to sexual dimorphisms in liver cancer.

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The Y-linked proto-oncogene TSPY contributes to poor prognosis of the male hepatocellular carcinoma patients by promoting the pro-oncogenic and suppressing the anti-oncogenic gene expression

Cited by 21 publications

References 95 publications

A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma

A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma

A novel RNA binding protein-associated prognostic model to predict overall survival in hepatocellular carcinoma patients

Potential dual functional roles of the Y‐linked RBMY in hepatocarcinogenesis

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