Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways

Zhang, Yiqun; Chen, Ken; Chandrashekar, Darshan S.; Varambally, Sooryanarayana; Creighton, Chad J.

doi:10.1038/s41467-022-30342-3

Cited by 92 publications

(96 citation statements)

References 73 publications

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“…An analysis of the individual BC stages showed that the CKAP2 expression was higher in all stages (stage 1–4) when compared to normal breast tissue ( Figure 3 E). Analysis of the CKAP2 protein levels in BC was performed using UALCAN based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database [ 30 , 48 ] ( Figure 3 F–H). As shown in Figure 3 F, protein expression levels of CKAP2 in BC were significantly increased compared to normal tissues ( p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

Knockdown of CKAP2 Inhibits Proliferation, Migration, and Aggregate Formation in Aggressive Breast Cancer

Santos

Ouellete

Diorio

et al. 2022

Cancers

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Loss of mitotic regulation is commonly observed in cancer and is a major cause of whole-chromosome aneuploidy. The identification of genes that play a role in the proper progression of mitosis can help us to understand the development and evolution of this disease. Here, we generated a list of proteins implicated in mitosis that we used to probe a patient-derived breast cancer (BC) continuum gene-expression dataset generated by our group by human transcriptome analysis of breast lesions of varying aggressiveness (from normal to invasive). We identified cytoskeleton-associated protein 2 (CKAP2) as an important mitotic regulator in invasive BC. The results showed that CKAP2 is overexpressed in invasive BC tumors when compared with normal tissues, and highly expressed in all BC subtypes. Higher expression of CKAP2 is also related to a worse prognosis in overall survival and relapse-free survival in estrogen receptor (ER)-positive and human epidermal growth factor receptor type 2 (HER2)-negative BC patients. Knockdown of CKAP2 in SKBR3 cells impaired cell proliferation and cell migration and reduced aggregate formation in a 3D culture. Our results show the important role of CKAP2 in BC tumorigenesis, and its potential utility as a prognostic marker in BC.

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Section: Resultsmentioning

confidence: 99%

Knockdown of CKAP2 Inhibits Proliferation, Migration, and Aggregate Formation in Aggressive Breast Cancer

Santos

Ouellete

Diorio

et al. 2022

Cancers

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“…The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN; ) is a public online database that provides protein expression analysis option using data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the International Cancer Proteogenome Consortium (ICPC) datasets ( 17 , 18 ). In this study, we compared the protein expression difference between primary UCEC tumor samples (n=100) and normal endometrial samples (n=31) using the data from CPTAC on ULCAN.…”

Section: Methodsmentioning

confidence: 99%

“…Cancer Proteogenome Consortium (ICPC) datasets (17,18). In this study, we compared the protein expression difference between primary UCEC tumor samples (n=100) and normal endometrial samples (n=31) using the data from CPTAC on ULCAN.…”

Section: The University Of Alabama At Birmingham Cancer Data Analysis...mentioning

confidence: 99%

RPP40 is a prognostic biomarker and correlated with tumor microenvironment in uterine corpus endometrial carcinoma

Tang

Tian²,

Min³

et al. 2022

Front. Oncol.

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Ribonuclease P/MRP Subunit P40 (RPP40), a component of ribonuclease P and multimeric ribonuclease P complex, was reported as one of the promoting factors for the chemoresistance of acute myeloid leukemia and a recurrence predictor of early-stage triple-negative breast cancer. However, the functional role of RPP40 in uterine corpus endometrial carcinoma (UCEC) is unclear. In this study, comprehensive bioinformatic analyses were conducted to explore the predictive role of RPP40 on UCEC diagnosis and prognosis, as well as the underlying mechanism. Differential analyses of multiple databases showed that both messenger RNA (mRNA) and the protein expression of RPP40 were significantly upregulated in UCEC tumor tissues. Furthermore, the RPP40 mRNA expression level was significantly correlated with the clinicopathological characteristics of UCEC patients, including the clinical stage, primary therapy outcome, histological type, histologic grade, overall survival event, disease-specific survival event, and progression-free interval event. Receiver operating characteristic (ROC) analysis showed that RPP40 was a reliable predictor for UCEC diagnosis with an area under the curve (AUC) of 0.775, a sensitivity of 0.829, and a specificity of 0.719. Kaplan–Meier, Cox regression, and nomogram analyses showed that high RPP40 expression was an independent prognostic factor for the 1-year, 3-year, and 5-year survival of UCEC patients. In addition, the enrichment analysis of RPP40-associated differentially expressed genes and correlation analyses showed that the expression of RPP40 was correlated with the regulation of extracellular matrix and immune cell infiltration. In conclusion, the upregulation of RPP40 is significantly correlated with the poor survival and tumor microenvironment of UCEC, suggesting that RPP40 is a promising biomarker of poor prognosis and a potential target of chemotherapy or immunotherapy in UCEC.

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“…Unlike other USP10 inhibitors, ubiquitin variant.10.1 (UbV.10.1) is a mixture of peptides and proteins with a high affinity for USP10. UbV.10.1 overexpression can promote the degradation of p53 by inhibiting USP10 (92). However, the antitumor effects of both CNYP and UbV.10.1 have yet to be explored.…”

Section: Usp10 Inhibitors and Other Modulators Of Usp10 Activitymentioning

confidence: 99%

Ubiquitin-specific peptidase 10, a deubiquitinating enzyme: Assessing its role in tumor prognosis and immune response

Chen²,

Huang³

et al. 2022

Front. Oncol.

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Ubiquitin-specific peptidase 10 (USP10) is a member of the ubiquitin-specific protease family that removes the ubiquitin chain from ubiquitin-conjugated protein substrates. We performed a literature search to evaluate the structure and biological activity of USP10, summarize its role in tumorigenesis and tumor progression, and discuss how USP10 may act as a tumor suppressor or a tumor-promoting gene depending on its mechanism of action. Subsequently, we elaborated further on these results through bioinformatics analysis. We demonstrated that abnormal expression of USP10 is related to tumorigenesis in various types of cancer, including liver, lung, ovarian, breast, prostate, and gastric cancers and acute myeloid leukemia. Meanwhile, in certain cancers, increased USP10 expression is associated with tumor suppression. USP10 was downregulated in kidney renal clear cell carcinoma (KIRC) and associated with reduced overall survival in patients with KIRC. In contrast, USP10 upregulation was associated with poor prognosis in head and neck squamous cell carcinoma (HNSC). In addition, we elucidated the novel role of USP10 in the regulation of tumor immunity in KIRC and HNSC through bioinformatics analysis. We identified several signaling pathways to be significantly associated with USP10 expression, such as ferroptosis, PI3K/AKT/mTOR, TGF-β, and G2/M checkpoint. In summary, this review outlines the role of USP10 in various forms of cancer, discusses the relevance of USP10 inhibitors in anti-tumor therapies, and highlights the potential function of USP10 in regulating the immune responses of tumors.

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Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways

Cited by 92 publications

References 73 publications

Knockdown of CKAP2 Inhibits Proliferation, Migration, and Aggregate Formation in Aggressive Breast Cancer

Knockdown of CKAP2 Inhibits Proliferation, Migration, and Aggregate Formation in Aggressive Breast Cancer

RPP40 is a prognostic biomarker and correlated with tumor microenvironment in uterine corpus endometrial carcinoma

Ubiquitin-specific peptidase 10, a deubiquitinating enzyme: Assessing its role in tumor prognosis and immune response

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