Dataset Information

C-Met and EPHA7 Receptor Tyrosine Kinases Are Related to Prognosis in Clear Cell Renal Cell Carcinoma: Focusing on the Association with Myoferlin Expression.

ABSTRACT: Receptor tyrosine kinases (RTKs) are important targets for clear cell renal cell carcinoma (ccRCC) treatment. Myoferlin is a strong regulator of RTKs. To identify myoferlin-associated RTKs and their prognostic implications in ccRCC, we investigated the expression of RTKs and myoferlin using proteome-based evaluation and immunohistochemical staining in tissue microarray. Multivariate Cox analysis adjusted for TNM stage and WHO grade was performed (n = 410 and 506). Proteomic analysis suggested c-Met and EPHA7 as novel candidates for myoferlin-associated RTKs. We immunohistochemically validated the positive association between c-Met and myoferlin expression. High c-Met expression was independently associated with overall (hazard ratio (HR) = 1.153-2.919) and cancer-specific survival (HR = 1.150-3.389). The prognostic effect of high c-Met expression was also determined in an independent cohort (overall survival, HR = 1.503-3.771). Although expression of EPHA7 and myoferlin was not correlated, EPHA7 expression was independently associated with progression-free (HR = 1.237-4.319) and cancer-specific survival (HR = 1.214-4.558). In addition, network-based prioritization showed co-functional enrichment of c-Met and myoferlin, suggesting a novel regulatory function of myoferlin in c-Met signaling. This study indicates that c-Met and EPHA7 might be useful prognostic biomarkers, and the presumed myoferlin/c-Met pathway could be a novel therapeutic target in ccRCC.

SUBMITTER: Jung M

PROVIDER: S-EPMC8870418 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

c-Met and EPHA7 Receptor Tyrosine Kinases Are Related to Prognosis in Clear Cell Renal Cell Carcinoma: Focusing on the Association with Myoferlin Expression.

Jung Minsun M Lee Seokhyeon S Moon Kyung Chul KC

Cancers 20220221 4

Receptor tyrosine kinases (RTKs) are important targets for clear cell renal cell carcinoma (ccRCC) treatment. Myoferlin is a strong regulator of RTKs. To identify myoferlin-associated RTKs and their prognostic implications in ccRCC, we investigated the expression of RTKs and myoferlin using proteome-based evaluation and immunohistochemical staining in tissue microarray. Multivariate Cox analysis adjusted for TNM stage and WHO grade was performed (<i>n</i> = 410 and 506). Proteomic analysis sugge ...[more]

PMID: 35205843

Similar Datasets

Project description:BACKGROUND:The receptor tyrosine kinases (RTKs) play critical roles in the development of cancers. Clear cell renal cell carcinoma (ccRCC) accounts for 75% of the RCC. The previous studies on the RTKs in ccRCCs mainly focused on their gene expressions. The activation and function of the RTKs in ccRCC have not been fully investigated. METHODS:In the present study, we analyzed the phosphorylation patterns of RTKs in human ccRCC patient samples, human ccRCC and papillary RCC cell lines, and other kidney tumor samples using human phospho-RTK arrays. We further established ccRCC patient-derived xenograft models in nude mice and assessed the effects of RTKIs (RTK Inhibitors) on the growth of these cancer cells. Immunofluorescence staining was used to detect the localization of keratin, vimentin and PDGFRβ in ccRCCs. RESULTS:We found that the RTK phosphorylation patterns of the ccRCC samples were all very similar, but different from that of the cell lines, other kidney tumor samples, as well as the adjacent normal tissues. 9 RTKs, EGFR1-3, Insulin R, PDGFRβ, VEGFR1, VEGFR2, HGFR and M-CSFR were found to be phosphorylated in the ccRCC samples. The adjacent normal tissues, on the other hand, had predominantly only two of the 4 EGFR family members, EGFR and ErbB4, phosphorylated. What's more, the RTK phosphorylation pattern of the xenograft, however, was different from that of the primary tissue samples. Treatment of the xenograft nude mice with corresponding RTK inhibitors effectively inhibited the Erk1/2 signaling pathway as well as the growth of the tumors. In addition, histological staining of the cancer samples revealed that most of the PDGFRβ expressing cells were localized in the vimentin-positive periepithelial stroma. CONCLUSIONS:Overall, we have identified a set of RTKs that are characteristically phosphorylated in ccRCCs. The phosphorylation of RTKs in ccRCCs were determined by the growing environments. These phosphorylated/activated RTKs will guide targeting drugs development of more effective therapies in ccRCCs. The synergistical inhibition of RTKIs combination on the ccRCC suggest a novel strategy to use a combination of RTKIs to treat ccRCCs.

Dataset Information

C-Met and EPHA7 Receptor Tyrosine Kinases Are Related to Prognosis in Clear Cell Renal Cell Carcinoma: Focusing on the Association with Myoferlin Expression.

Publications

c-Met and EPHA7 Receptor Tyrosine Kinases Are Related to Prognosis in Clear Cell Renal Cell Carcinoma: Focusing on the Association with Myoferlin Expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets