CDCA4 as a novel molecular biomarker of poor prognosis in patients with lung adenocarcinoma

Tan, Jianlong; Chen, Fengyu; Ouyang, Bo; Li, Xiuying; Zhang, Weidong; Gao, Xiaowen

doi:10.3389/fonc.2022.865756

Cited by 7 publications

(5 citation statements)

References 46 publications

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“…CDCA4 is a marker for poor prognosis in LUAD, [ 43 ] a finding that is consistent with our results. CDCA4 expression increases in most tumors and is associated with poor OS and Disease free survival(DFS).…”

Section: Discussionsupporting

confidence: 92%

CDCA gene family promotes progression and prognosis in lung adenocarcinoma

Liu,

Zhu,

Zhao

et al. 2024

Medicine

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Background: The cell division cycle-associated (CDCA) family participates in the cell cycle, and the dysregulation of its expression is associated with the development of several types of cancers. However, the roles of CDCAs in lung adenocarcinomas (LUAD) have not been investigated in systematic research. Methods: Using data retrieved from The Cancer Genome Atlas (TCGA), the expression of CDCAs in LUAD and normal tissues was compared, and survival analysis was performed using the data. Also, the correlation between clinical characteristics and the expression of CDCAs was assessed. Using data from cBioPortal, we investigated genetic alterations in CDCAs and their prognostic implications. Immunohistochemical analyses were performed to validate our findings from TCGA data. Following this, we created a risk score model to develop a nomogram. We also performed gene set enrichment analyses (GSEA), gene ontology, and KEGG pathway analysis. We used Timer to analyze the correlation between immune cell infiltration, tumor purity, and expression data. Results: Our results indicated that all CDCAs were expressed at high levels in LUAD; this could be associated with poor overall survival, as indicated in TCGA data. Univariate and multivariate Cox analyses revealed that CDCA4/5 could serve as independent risk factors. The results of immunohistochemical analyses confirmed our results. Based on the estimation of expression levels, clinical characteristics, alterations, and immune infiltration, the low-risk group of CDCA4/5 had a better prognosis than the high-risk group. Immune therapy is also a potential treatment option. Conclusion: In conclusion, our findings indicate that CDCAs play important roles in LUAD, and CDCA4/5 can serve as diagnostic and prognostic biomarkers and therapeutic targets in LUAD.

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Section: Discussionsupporting

confidence: 92%

CDCA gene family promotes progression and prognosis in lung adenocarcinoma

Liu,

Zhu,

Zhao

et al. 2024

Medicine

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“…[ 16 ] Furthermore, lung adenocarcinoma cells are more able to proliferate, migrate, and invade when CDCA4 expression is high. [ 14 , 15 ] Given these diverse roles, CDCA4 shows promise as an important therapeutic target for malignant tumors in the future.…”

Section: Discussionmentioning

confidence: 99%

“…In non-tumor contexts, lower expression levels of CDCA4 have been associated with inhibited myocardial cell proliferation and displayed a negative correlation with heart failure severity in patients. [13][14][15][16][17] CDCA4 has been confirmed to participate in tumorigenesis and metastasis in various cancers. However, its role in primary liver cancer remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Exploring the role of CDCA4 in liver hepatocellular carcinoma using bioinformatics analysis and experiments

Liang,

Long,

Zheng

et al. 2024

Medicine

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Liver hepatocellular carcinoma (LIHC) encompasses diverse therapeutic approaches, among which targeted therapy has gained significant prominence in recent years. The identification of numerous targets and the increasing clinical application of targeted drugs have greatly improved LIHC treatment. However, the precise role of CDCA4 (Cell Division Cycle Associated 4), as well as its underlying mechanisms and prognostic implications in LIHC, remains unclear. CDCA4 expression levels in LIHC were analyzed using multiple databases including the cancer genome atlas (TCGA), gene expression profiling interactive analysis (GEPIA), and ULCAN, as well as the datasets E_TABM_36, GSE144269, GSE14520, and GSE54236. The prognostic value of CDCA4 was then evaluated. Subsequently, the association between CDCA4 and immune cells was investigated. Enrichment analysis (GSEA) was utilized to investigate the functional roles and pathways linked to CDCA4. Additionally, the methylation patterns and drug sensitivity of CDCA4 were examined. A predictive model incorporating immune genes related to CDCA4 was developed. The TISCH dataset was used to investigate the single-cell expression patterns of CDCA4. Finally, validation of CDCA4 expression levels was conducted through RT-PCR, Western blotting, and immunohistochemistry. CDCA4 exhibited significant overexpression in LIHC and demonstrated significant correlations with clinical features. High expression of CDCA4 is associated with a poorer prognosis. Analysis of immune infiltration and enrichment revealed its association with the immune microenvironment. Furthermore, its expression is correlated with methylation and mutation patterns. CDCA4 is associated with 19 drugs. Prognostic models utilizing CDCA4 demonstrate favorable effectiveness. T cell subtypes were found to be associated with CDCA4 through single-cell analysis. The conclusive experiment provided evidence of significant upregulation of CDCA4 in LIHC. The high expression of CDCA4 in LIHC is associated with prognostic significance and is highly expressed in T cell subtypes, providing a new therapeutic target and potential therapeutic strategy for LIHC.

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“…Pan cancer analysis revealed that a great number of tumors highly expressed CDCA4, which was associated with poor survival and different immune infiltration characteristics ( Fang et al, 2022 ). In particular, CDCA4 was found to be a marker for poor OS in patients with LUAD ( Tan et al, 2022 ). Although there are not evidences showing direct association between CDCA4 and RA, previous studies have shown that transcription factors in E2F family were enriched in RA ( Takeshita et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of shared gene signature between rheumatoid arthritis and lung adenocarcinoma helps to predict the prognosis and tumor microenvironment of the LUAD patients

Shi,

Zou,

2024

Front. Mol. Biosci.

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Introduction: Rheumatoid arthritis (RA) is a common chronic autoimmune disease with high incidence rate and high disability rate. One of the top complications is cancer, especially lung adenocarcinoma (LUAD). However, the molecular mechanisms linking RA and LUAD are still not clear. Therefore, in this study, we tried to identify the shared genetic signatures and local immune microenvironment between RA and LUAD and construct a clinical model for survival prediction.Methods: We obtained gene expression profiles and clinical information of patients with RA and LUAD from GEO and TCGA datasets. We performed differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA) to discover the shared genes between RA and LUAD. Then, COX regression and LASSO analysis were employed to figure out genes significantly associated with survival. qRT-PCR and Western blot were utilized to validate the expression level of candidate genes. For clinical application, we constructed a nomogram, and also explored the value of RALUADS in characterizing immune infiltration features by CIBERSORT and xCell. Finally, responses to different drug therapy were predicted according to different RALUADS.Results: Our analysis identified two gene sets from differentially expressed genes and WGCNA gene modules of RA and LUAD. Filtered by survival analysis, three most significant shared genes were selected, CCN6, CDCA4 and ERLIN1, which were all upregulated in tumors and associated with poor prognosis. The three genes constituted RA and LUAD score (RALUADS). Our results demonstrated that RALUADS was higher in tumor patients and predicted poor prognosis in LUAD patients. Clinical nomogram combining RALUADS and other clinicopathological parameters had superior performance in survival prediction (AUC = 0.722). We further explored tumor immune microenvironment (TME) affected by RALUADS and observed RALUADS was closely related to the sensitivity of multiple immune blockades, chemotherapy and targeted drugs.Conclusion: Our findings suggest that there are shared physiopathologic processes and molecular profiles between RA and LUAD. RALUADS represents an excellent prognosis predictor and immune-related biomarker, which can be applied to select potential effective drugs and for LUAD patients with RA.

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CDCA4 as a novel molecular biomarker of poor prognosis in patients with lung adenocarcinoma

Cited by 7 publications

References 46 publications

CDCA gene family promotes progression and prognosis in lung adenocarcinoma

CDCA gene family promotes progression and prognosis in lung adenocarcinoma

Exploring the role of CDCA4 in liver hepatocellular carcinoma using bioinformatics analysis and experiments

Construction of shared gene signature between rheumatoid arthritis and lung adenocarcinoma helps to predict the prognosis and tumor microenvironment of the LUAD patients

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