Show simple item record

AuthorAl Sharie, Ahmed H.
AuthorAbu Zahra, Abdulmalek M.
AuthorEl-Elimat, Tamam
AuthorDarweesh, Reem F.
AuthorAl-Khaldi, Ayah K.
AuthorAbu Mousa, Balqis M.
AuthorAmer, Mohammad S. Bani
AuthorAl Zu'bi, Yazan O.
AuthorAl-Kammash, Kinda
AuthorAbu Lil, Alma
AuthorAl Malkawi, Abubaker A.
AuthorAlazzeh, Zainab
AuthorAlali, Feras Q.
Available date2023-11-19T05:45:34Z
Publication Date2023
Publication NameMedicine (United States)
ResourceScopus
ISSN257974
URIhttp://dx.doi.org/10.1097/MD.0000000000035004
URIhttp://hdl.handle.net/10576/49427
AbstractCell cycle regulatory proteins plays a pivotal role in the development and progression of many human malignancies. Identification of their biological functions as well as their prognostic utility presents an active field of research. As a continuation of the ongoing efforts to elucidate the molecular characteristics of clear cell renal cell carcinoma (ccRCC); we present a comprehensive bioinformatics study targeting the prognostic and mechanistic role of cyclin-dependent kinase inhibitor 3 (CDKN3) in ccRCC. The ccRCC cohort from the Cancer Genome Atlas Program was accessed through the UCSC Xena browser to obtain CDKN3 mRNA expression data and their corresponding clinicopathological variables. The independent prognostic signature of CDKN3 was evaluated using univariate and multivariate Cox logistic regression analysis. Gene set enrichment analysis and co-expression gene functional annotations were used to discern CDKN3-related altered molecular pathways. The tumor immune microenvironment was evaluated using TIMER 2.0 and gene expression profiling interactive analysis. CDKN3 upregulation is associated with shortened overall survival (hazard ratio [HR] = 2.325, 95% confident interval [CI]: 1.703–3.173, P < .0001) in the Cancer Genome Atlas Program ccRCC cohort. Univariate (HR: 0.426, 95% CI: 0.316–0.576, P < .001) and multivariate (HR: 0.560, 95% CI: 0.409–0.766, P < .001) Cox logistic regression analyses indicate that CDKN3 is an independent prognostic variable of the overall survival. High CDKN3 expression is associated with enrichment within the following pathways including allograph rejection, epithelial–mesenchymal transition, mitotic spindle, inflammatory response, IL-6/JAK/STAT3 signaling, spermatogenesis, TNF-α signaling via NF-kB pathway, complement activation, KRAS signaling, and INF-γ signaling. CDKN3 is also associated with significant infiltration of a wide spectrum of immune cells and correlates remarkably with immune-related genes. CDKN3 is a poor prognostic biomarker in ccRCC that alters many molecular pathways and impacts the tumor immune microenvironment.
Languageen
PublisherLippincott Williams and Wilkins
Subjectbioinformatics
ccRCC
CDKN3
clear cell renal cell carcinoma
cyclin-dependent kinase inhibitor 3
TCGA
TitleCyclin dependent kinase inhibitor 3 (CDKN3) upregulation is associated with unfavorable prognosis in clear cell renal cell carcinoma and shapes tumor immune microenvironment: A bioinformatics analysis
TypeArticle
PaginationE35004
Issue Number36
Volume Number102
dc.accessType Open Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record