Identifies KCTD5 as a novel cancer biomarker associated with programmed cell death and chemotherapy drug sensitivity

Abstract

Background More and more studies have demonstrated that potassium channel tetramerization domain-containing 5 (KCTD5) plays an important role in the development of cancer, but there is a lack of comprehensive research on the biological function of this protein in pan-cancer. This study systematically analyzed the expression landscape of KCTD5 in terms of its correlations with tumor prognosis, the immune microenvironment, programmed cell death, and drug sensitivity. Methods We investigated a number of databases, including TCGA, GEPIA2, HPA, TISIDB, PrognoScan, GSCA, CellMiner, and TIMER2.0. The study evaluated the expression of KCTD5 in human tumors, as well as its prognostic value and its association with genomic alterations, the immune microenvironment, tumor-associated fibroblasts, functional enrichment analysis, and anticancer drug sensitivity. Real-time quantitative PCR and flow cytometry analysis were performed to determine the biological functions of KCTD5 in lung adenocarcinoma cells. Results The results indicated that KCTD5 is highly expressed in most cancers and that its expression is significantly correlated with tumor prognosis. Moreover, KCTD5 expression was related to the immune microenvironment, infiltration by cancer-associated fibroblasts, and the expression of immune-related genes. Functional enrichment analysis revealed that KCTD5 is associated with apoptosis, necroptosis, and other types of programmed cell death. In vitro experiments showed that knockdown of KCTD5 promoted apoptosis of A549 cells. Correlation analysis confirmed that KCTD5 was positively correlated with the expression of the anti-apoptotic genes Bcl-xL and Mcl-1. Additionally, KCTD5 was significantly associated with sensitivity to multiple antitumor drugs. Conclusion Our results suggest that KCTD5 is a potential molecular biomarker that can be used to predict patient prognosis, immunoreactions and drug sensitivity in pan-cancer. KCTD5 plays an important role in regulating programmed cell death, especially apoptosis.

Interactions of Histone Deacetylase 6 with DNA Damage Repair Factors Strengthen its Utility as a Combination Drug Target in High-Grade Serous Ovarian Cancer

“…Of these 32 genes, many have been identified as having varying roles in ovarian cancer progression and prognosis. Elevated abundances of AHNAK, ANXA1, and LAMA3 have been correlated with suppressed ovarian cancer growth and improved survival. − CHD4, PFKFB3, and RSF1 have been associated with the regulation of drug response. − The expression of FLI-1, KCD5, and PRSS3 has been associated with poor survival, and these proteins are potential prognostic markers. − TP53 is also strongly linked to HGSOC as it is mutated in most HGSOC patients, leading to a gain or loss of function . Other DNA damage repair factors were also identified as significant across the CD1 and CD2 conditions: PRDKC, PARP9, and XRCC6 (Figure D, Table S5).…”

CD8+ T cell‑related KCTD5 contributes to malignant progression and unfavorable clinical outcome of patients with triple‑negative breast cancer

“…KCTD5 may serve as a modulator of cell migration by influencing cell motility and focal adhesion dynamics, potentially via Rac1 activity and Ca 2+ signaling pathways, which has been reported by previous studies ( 39 , 47 , 48 ). KCTD5 is a cancer marker associated with programmed cell death ( 49 ). KCTD5 knockdown increases the apoptosis of human lung cancer cell line A549 ( 49 ).…”

“…KCTD5 is a cancer marker associated with programmed cell death ( 49 ). KCTD5 knockdown increases the apoptosis of human lung cancer cell line A549 ( 49 ). These findings suggest the potential value in downregulating KCTD5 in TNBC treatment.…”

KCTD5 Forms Hetero-Oligomeric Complexes with Various Members of the KCTD Protein Family

“…This raises the possibility that KCTD5 may serve a broader role as a scaffold partner with other KCTD proteins. In the context of disease, KCTD5 has been identified as a novel cancer biomarker [ 18 ] that exhibits high expression in some lung adenocarcinoma tumors [ 19 ]. Intriguingly, the expression of other KCTD members decreased in the advanced tumor stage [ 19 ], suggesting that interplay between KCTDs may play a role in disease progression.…”