A Novel 8-Gene Prognostic Signature for Survival Prediction of Uveal Melanoma

Tang, Zhongjun; Cai, Kebo

doi:10.1155/2021/6693219

Cited by 3 publications

(9 citation statements)

References 26 publications

(28 reference statements)

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Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

“…Recently, Tang and Cai generated a model for UM prognosis prediction based on the data of the gene expression microarray GEO data set GSE22138, which comprised a cohort of 63 patients UM patients [ 154 ]. Initially, they used WGCNA and identified 41 hub genes that are associated with UM metastases [ 154 ]. Afterwards, they applied a LASSO COX regression methodology to identify relevant genes and build a gene expression signature with prognostic significance, which comprises eight genes ( EIF1B, MEGF10, PHLDA1, RPL10A, RPL15, SLC25A38, TFDP2 and TIPARP ) and named Uveal Melanoma Metastasis Prediction Score (UMPS) [ 154 ].…”

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

“…Initially, they used WGCNA and identified 41 hub genes that are associated with UM metastases [ 154 ]. Afterwards, they applied a LASSO COX regression methodology to identify relevant genes and build a gene expression signature with prognostic significance, which comprises eight genes ( EIF1B, MEGF10, PHLDA1, RPL10A, RPL15, SLC25A38, TFDP2 and TIPARP ) and named Uveal Melanoma Metastasis Prediction Score (UMPS) [ 154 ]. The individual coefficient by LASSO COX regression of RPL10A was demonstrated to be associated with a high risk of metastases, whereas the remainder seven genes were shown to be protective [ 154 ].…”

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

“…Afterwards, they applied a LASSO COX regression methodology to identify relevant genes and build a gene expression signature with prognostic significance, which comprises eight genes ( EIF1B, MEGF10, PHLDA1, RPL10A, RPL15, SLC25A38, TFDP2 and TIPARP ) and named Uveal Melanoma Metastasis Prediction Score (UMPS) [ 154 ]. The individual coefficient by LASSO COX regression of RPL10A was demonstrated to be associated with a high risk of metastases, whereas the remainder seven genes were shown to be protective [ 154 ]. GSEA analysis showed that the high-risk of metastasis group was associated with complement, E2F targets, G2M checkpoints and unfolded protein response pathways, while no differences in the immune cell proportions were registered between low and high risk groups [ 154 ].…”

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

“…The individual coefficient by LASSO COX regression of RPL10A was demonstrated to be associated with a high risk of metastases, whereas the remainder seven genes were shown to be protective [ 154 ]. GSEA analysis showed that the high-risk of metastasis group was associated with complement, E2F targets, G2M checkpoints and unfolded protein response pathways, while no differences in the immune cell proportions were registered between low and high risk groups [ 154 ]. The UMPS model was later externally validated using the 80-patient TCGA cohort and the 29-patient GSE27831 cohort of UM patients [ 154 ].…”

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

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Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.

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Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

Section: Gene Signatures As Novel Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

See 3 more Smart Citations

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma

et al. 2022

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Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.

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Low Level of PALMD Contributes to the Metastasis of Uveal Melanoma

Cai

Hua

et al. 2022

Front. Oncol.

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Uveal melanoma (UM) is a highly aggressive disease. There is an urgent need to develop the metastasis prediction markers of UM. This study aims to detect the key role of PALMD in UM metastasis. Transcriptome sequencing results of 2 sets of UM metastatic samples (GSE22138 and GSE156877) were downloaded from the Gene Expression Omnibus (GEO), and 18 overlapping differentially expressed genes were screened out, including PALMD. PALMD was significantly underexpressed in metastatic UM tissue. Low expression of PALMD was associated with poor prognosis in UM patients. The decreased expression of PALMD promoted the invasion and migration of 92-1 and Mel270 cells, while the high expression of PALMD inhibited the invasion and migration of UM cells. Furthermore, the levels of matrix metallopeptidase (MMP) 2 and MMP9 increased after transfection of siRNAs specifically targeting PALMD, whereas the levels of MMP2 and MMP9 were decreased after PALMD overexpression. However, PALMD did not affect the proliferation of UM cells. In addition, ZNF263 promoted the transcription of PALMD through the putative binding sequence using the JASPAR database, luciferase reporter gene analysis and chromatin immunoprecipitation assay. In summary, the expression of PALMD regulated by ZNF263 plays an important role in UM metastasis.

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A Novel 8-Gene Prognostic Signature for Survival Prediction of Uveal Melanoma

Cited by 3 publications

References 26 publications

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma

Low Level of PALMD Contributes to the Metastasis of Uveal Melanoma

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