Non-SMC condensin I complex subunit D2 (NCAPD2) reveals its prognostic and immunologic features in human cancers

Abstract

Non-SMC condensin I complex subunit D2 (NCAPD2) is overexpressed in some malignant tumors. However, there are few studies on the function of NCAPD2 in pan-cancer. We used the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN to analyze NCAPD2 expression and promoter methylation levels in 33 tumors and normal samples. We performed immunohistochemistry (IHC) on liver cancer and corresponding normal tissues to examine NCAPD2 protein expression in LIHC. Kaplan-Meier survival and univariate regression analyses were performed to explore the pan-cancer clinical significance of NCAPD2. Moreover, correlative analysis between NCAPD2 expression and clinical characteristics, immune cell infiltration, immune checkpoints, immune regulators, tumor mutation burden (TMB), microsatellite instability (MSI), ribonucleic acid (RNA) methylation regulators, and drug sensitivity was conducted using data from TCGA. We also investigated the effects of NCAPD2 expression on immunotherapy efficacy and prognosis. Gene set enrichment analysis (GSEA) was conducted using NCAPD2. Bioinformatic analysis showed that NCAPD2 was overexpressed in most tumors and correlated with the clinical characteristics of some cancers. IHC results demonstrated that NCAPD2 protein expression was higher in LIHC than in normal liver. NCAPD2 expression was linked with T stage, clinical stage, and histologic grade in LIHC. Overexpression of NCAPD2 resulted in poor overall survival, and disease-specific survival in adrenocortical carcinoma, kidney renal papillary cell carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, lung adenocarcinoma, mesothelioma, pancreatic adenocarcinoma, sarcoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma. NCAPD2 was considered an independent biomarker by Cox regression in LIHC. The time ROC curve demonstrated that the survival rate of 1-, 3-, and 5-year OS and DSS in LIHC was above 0.6. The expression of NCAPD2 was significantly correlated with immune cell infiltration, immune checkpoints, TMB, MSI, and RNA methylation regulators in several tumors. NCAPD2 had a high predictive value for immunotherapy efficiency in certain tumors. In our study, drugs sensitive to NCAPD2 protein were screened by sensitivity analysis. GSEA analysis showed that NCAPD2 mainly participated in the G2M checkpoint, mitotic spindle, and KRAS-signaling. NCAPD2 may act as a prognostic molecular marker in most cancers.

NCAPD2 serves as a potential prognostic biomarker for lung adenocarcinoma and promotes cell proliferation, migration, invasion and cell cycle <i>in vitro</i>

“…Currently, there is a growing acknowledgment of the pivotal role played by the immune system in the progression of tumors [44]. Multiple studies have shown that NCAPD2 impacts immune cell infiltration in various tumors, nevertheless, its precise role in LUAD remains uncertain [23]. Therefore, our study delves into the intricate relationship between NCAPD2 and immune cell infiltration, utilizing the CIBERSORT algorithm and validating our findings through the TIMER database.…”

“…NCAPD2 assumes the role of a non-SMC subunit in condensin I, influencing the function of another non-SMC subunit of condensin I, sister chromatid separation, and chromosome alignment during metaphase [12]. Although previous studies have hinted at a potential connection between NCAPD2 and the prognosis of LUAD, its precise function and underlying molecular mechanisms remain elusive [23]. The objective of this research was to clarify the involvement of NCAPD2 in the progression of LUAD, with the intention of identifying a new potential prognostic biomarker and treatment targe.…”

“…The Western blot results indicated that NCAPD2 knockdown led to decreased protein levels of CyclinA2, CDK2 and CDK6 in both cell types, but there was no significant difference in CyclinD1 or CDK4 levels. Previous research has indicated that NCAPD2 co-expressed genes are enriched in the MYC target pathway in various tumors [23]. Additionally, c-Myc and its induced genes play crucial roles in cell cycle control and cell growth [36].…”

“…As a component of condensin I, NCAPD2 is implicated in a range of diseases, including Alzheimer's disease, microcephaly, Parkinson's disease, and various neurodevelopmental disorders [20][21][22]. Furthermore, multiple studies have substantiated the engagement of NCAPD2 in the processes of tumorigenesis and progression [23][24][25][26]. For example, NCAPD2 is overexpressed in breast cancer and promotes its development through transcriptional activation of CDK1.…”

Unveiling the Significance of NCAP Family Genes in Adrenocortical Carcinoma and Adenoma Pathogenesis: A Molecular Bioinformatics Exploration

“…Among the 6 NCAP family genes, including NCAPG, NCAPG2, NCAPH, NCAPH2, NCAPD2, and NCAPD3, recent studies have highlighted their possible significance in various clinical disorders. 23 - 25 …”