Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression

Wang, Jing; Lei, Minxiang; Xu, Zhijie

doi:10.7717/peerj.11813

Cited by 4 publications

(1 citation statement)

References 62 publications

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“…When we evaluate the compromising 21 nodes of this PTC‐module, we find that several of these genes have already been individually associated with thyroid cancer, which further strengthens our confidence in our observations when we consider them as systems biomarkers. The following genes: PROS1, 42 DCSTAMP, 43 DUSP5, 44 AHNAK2, 45 SLC34A2, 46 FN1, 47 C16orf89, 48 FHL1, 49 TPO, 50 DIO1 51 has been associated with thyroid cancer and/or PTC.…”

Section: Discussionmentioning

confidence: 99%

Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

Kori,

Temiz,

Gov

2023

J Cellular Molecular Medi

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Papillary thyroid carcinoma (PTC) is one of the most common endocrine carcinomas worldwide and the aetiology of this cancer is still not well understood. Therefore, it remains important to understand the disease mechanism and find prognostic biomarkers and/or drug candidates for PTC. Compared with approaches based on single‐gene assessment, network medicine analysis offers great promise to address this need. Accordingly, in the present study, we performed differential co‐expressed network analysis using five transcriptome datasets in patients with PTC and healthy controls. Following meta‐analysis of the transcriptome datasets, we uncovered common differentially expressed genes (DEGs) for PTC and, using these genes as proxies, found a highly clustered differentially expressed co‐expressed module: a ‘PTC‐module’. Using independent data, we demonstrated the high prognostic capacity of the PTC‐module and designated this module as a prognostic systems biomarker. In addition, using the nodes of the PTC‐module, we performed drug repurposing and text mining analyzes to identify novel drug candidates for the disease. We performed molecular docking simulations, and identified: 4‐demethoxydaunorubicin hydrochloride, AS605240, BRD‐A60245366, ER 27319 maleate, sinensetin, and TWS119 as novel drug candidates whose efficacy was also confirmed by in silico analyzes. Consequently, we have highlighted here the need for differential co‐expression analysis to gain a systems‐level understanding of a complex disease, and we provide candidate prognostic systems biomarker and novel drugs for PTC.

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Section: Discussionmentioning

confidence: 99%

Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

Kori,

Temiz,

Gov

2023

J Cellular Molecular Medi

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LncRNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated low PROS1 expression is an onco-immunological biomarker in low-grade gliomas: a pan-cancer analysis with experimental verification

2022

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Background Glioma is the most common cancer in the central nervous system, and low grade gliomas are notorious for many types of tumors and heterogeneity. PROS1 not only plays an important role in the blood coagulation system, and recent studies have found that it was correlated with the development of tumors, especially related to tumor immune infiltration. However, the study of underlying role and mechanism of PROS1 in gliomas, especially in low-grade gliomas, is almost absent. Methods We integrated the information of patients with LGG in The Cancer Genome Atlas (TCGA) cohort and Chinese Glioma Genome Atlas (CGGA) cohort. Then, we systematically demonstrated the differences and prognostic prognosis value of PROS1 based on multi-omics analyses. In addition, Cell counting kit-8 (CCK-8) assay, colony formation assay, 5-Ethynyl-2’-deoxyuridine (EdU) incorporation assay, and Transwell assays were performed to evaluate cell proliferation and invasion. qRT-PCR and immunohistochemistry were used to evaluate the expression of PROS1 in LGG. Results Various bioinformatics approaches revealed that PROS1 was a valuable prognostic marker and may influence tumour development via distinct mechanisms, including expression of DNA methyltransferase, RNA modification, and DNA mismatch repair system genes, copy number variation, single nucleotide variation frequency, genomic heterogeneity, cancer stemness, DNA methylation, and alternative PROS1 splicing. Our analyses indicated that the long non-coding RNA RP3-525N10.2 may “decoy” or “guide” the transcription factor NFKB1 and prevent its association with PROS1, thereby reducing PROS1 expression and improving poor LGG prognosis. PROS1 expression was also closely associated with tumour infiltration by immune cells, especially tumour-associated macrophages, as well as the expression of various immune checkpoint inhibitors, immunomodulators, and immune cell markers. Conclusion long non-coding RNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated PROS1 expression could serve as a biomarker for cancer diagnosis, prognosis, therapy selection, and follow-up in LGG patients.

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Quantitative proteomics analysis of papillary thyroid carcinoma reveals Protein S, Clusterin, and Leucine-rich α-2-glycoprotein 1 as potential prognostic protein biomarkers

Le,

Sun,

et al. 2023

Preprint

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Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The primary challenge is identifying patient subgroups with PTC and choosing the most effective treatment approach. Results To explore the differently expressed proteins (DEPs) between high and low recurrent-risk PTCs, we collected 15 tissues comprising high (n = 7) and low (n = 8) recurrent-risk groups from PTC. The samples were detected by tandem mass tag labeling proteomics. Using TCGA (The Cancer Genome Atlas) data on thyroid cancer, prognosis-related DEPs were identified. Furthermore, an immunohistochemistry (IHC) stain of 53 cases of PTC tumors was adopted to validate the relation of potential biomarkers with prognosis. We identified 8,958 proteins from the 15 samples, with 95 DEPs obtained by comparing high and low-recurrent-risk groups, including 38 up-regulated and 57 down-regulated proteins. Three down-regulated proteins [Protein S (PROS1), Clusterin (CLU), and Leucine-rich α-2-glycoprotein 1 (LRG1)] were found to be significantly associated with poor overall survival in thyroid cancer using differential analysis and Kaplan-Meier survival analysis. IHC results showed low or moderated expressions of PROS1, CLU, and LRG1 were significantly associated with high-risk clinicopathologic characteristics of PTC. PTC patients with higher expression of PROS1, CLU, and LRG1 had better progression-free survival than those with low or moderate expression. Conclusions Our study identified PROS1, CLU, and LRG1 as novel prognostic biomarkers in PTC.

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Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression

Cited by 4 publications

References 62 publications

Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

LncRNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated low PROS1 expression is an onco-immunological biomarker in low-grade gliomas: a pan-cancer analysis with experimental verification

Quantitative proteomics analysis of papillary thyroid carcinoma reveals Protein S, Clusterin, and Leucine-rich α-2-glycoprotein 1 as potential prognostic protein biomarkers

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