Pan-cancer Analysis Identifies As a Novel Prognostic Marker Associated with Immune Infiltration in Lung Adenocarcinoma Through Bioinformatics Analysis

Overview

Journal Transl Cancer Res

Specialty Oncology

Date 2022 Sep 12

PMID 36093552

Authors

Hao Yang

Xueqiang Wei

Liren Zhang

Li Xiang

Ping Wang

Affiliations

Soon will be listed here.

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung malignancy. However, the expression of cell division cycle-associated protein-3 () and its significance in LUAD remain unclear. In this study, we investigated the functional role of in LUAD through bioinformatics analysis and expected to provide a new direction for clinical treatment.

Methods: The expression of was analyzed by online database. The association between the expression of and clinical parameters with LUAD was explored in TCGA. Survival and independent prognostic analysis were performed by TCGA database and the GSE30219 and GSE31210 datasets. Furthermore, Enrichment analyses were conducted to analyze the functions of . Afterward, the relationship between and immune infiltration was investigated. Additionally, a competing endogenous RNA (ceRNA) regulatory network related to was constructed. Finally, expression was validated in clinical tissues by immunohistochemistry (IHC), real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting (WB).

Results: expression was upregulated in 20 tumors and was significantly higher in LUAD compared with normal tissues in3 datasets. In addition, was significantly correlated with age, gender, stage, N, and smoking status. Kaplan-Meier survival curves showed that LUAD samples with higher expression were associated with poorer overall survival (OS) and disease-free survival (DFS). Univariate Cox regression analysis showed that the p value of expression was less than 0.05 (P<0.05) and it appeared in the results of multivariate Cox regression analysis (HR ≥1), indicating that can be used as an independent prognostic factor for LUAD. Intriguingly, Gene Set Enrichment Analysis (GSEA) suggested that was correlated with DNA-related terms and metabolic-related pathways in LUAD. expression was correlated with four immune scores and 14 immune cells in different groups. Next, a ceRNA network was constructed with , and the experimental results of IHC, qRT-PCR, and WB were consistent with the bioinformatic analysis.

Conclusions: could serve as a prognostic biomarker for LUAD.

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References

Li K, Li S, Tang S, Zhang M, Ma Z, Wang Q . KIF22 promotes bladder cancer progression by activating the expression of CDCA3. Int J Mol Med. 2021; 48(6). PMC: 8522959. DOI: 10.3892/ijmm.2021.5044. View

Sahin K, Shah E, Ferguson G, Molloy C, Kalita-de Croft P, Hayes S . Elevating CDCA3 Levels Enhances Tyrosine Kinase Inhibitor Sensitivity in TKI-Resistant EGFR Mutant Non-Small-Cell Lung Cancer. Cancers (Basel). 2021; 13(18). PMC: 8466783. DOI: 10.3390/cancers13184651. View

Gao S, Li N, Wang S, Zhang F, Wei W, Li N . Lung Cancer in People's Republic of China. J Thorac Oncol. 2020; 15(10):1567-1576. DOI: 10.1016/j.jtho.2020.04.028. View

Gu P, Yang D, Zhu J, Zhang M, He X . Bioinformatics analysis of the clinical relevance of CDCA gene family in prostate cancer. Medicine (Baltimore). 2022; 101(5):e28788. PMC: 8812703. DOI: 10.1097/MD.0000000000028788. View

Bade B, Dela Cruz C . Lung Cancer 2020: Epidemiology, Etiology, and Prevention. Clin Chest Med. 2020; 41(1):1-24. DOI: 10.1016/j.ccm.2019.10.001. View

Zou Y, Jing C, Liu L, Wang T . Serum microRNA-135a as a diagnostic biomarker in non-small cell lung cancer. Medicine (Baltimore). 2019; 98(50):e17814. PMC: 6922492. DOI: 10.1097/MD.0000000000017814. View

Nadal E, Massuti B, Domine M, Garcia-Campelo R, Cobo M, Felip E . Immunotherapy with checkpoint inhibitors in non-small cell lung cancer: insights from long-term survivors. Cancer Immunol Immunother. 2019; 68(3):341-352. PMC: 11028247. DOI: 10.1007/s00262-019-02310-2. View

Hutchinson B, Shroff G, Truong M, Ko J . Spectrum of Lung Adenocarcinoma. Semin Ultrasound CT MR. 2019; 40(3):255-264. DOI: 10.1053/j.sult.2018.11.009. View

Zhang K, Hu H, Xu J, Qiu L, Chen H, Jiang X . Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3. Diagn Pathol. 2020; 15(1):133. PMC: 7592370. DOI: 10.1186/s13000-020-01048-1. View

10.

Yu J, Hua R, Zhang Y, Tao R, Wang Q, Ni Q . DNA hypomethylation promotes invasion and metastasis of gastric cancer cells by regulating the binding of SP1 to the CDCA3 promoter. J Cell Biochem. 2019; 121(1):142-151. DOI: 10.1002/jcb.28993. View

11.

Gao T, Ji Y . Long Noncoding RNA LINC00707 Accelerates Tumorigenesis and Progression of Bladder Cancer via Targeting miR-145/CDCA3 Regulatory Loop. Urol Int. 2021; 105(9-10):891-905. DOI: 10.1159/000514388. View

12.

Zheng P, Wu K, Gao Z, Li H, Li W, Wang X . [Retracted] KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3. Int J Mol Med. 2023; 52(1). PMC: 10249579. DOI: 10.3892/ijmm.2023.5265. View

13.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

14.

Dou D, Ren X, Han M, Xu X, Ge X, Gu Y . CircUBE2D2 (hsa_circ_0005728) promotes cell proliferation, metastasis and chemoresistance in triple-negative breast cancer by regulating miR-512-3p/CDCA3 axis. Cancer Cell Int. 2020; 20:454. PMC: 7491078. DOI: 10.1186/s12935-020-01547-7. View

15.

Kildey K, Gandhi N, Sahin K, Shah E, Boittier E, Duijf P . Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy. Commun Biol. 2021; 4(1):638. PMC: 8163776. DOI: 10.1038/s42003-021-02136-8. View

16.

Miller K, Nogueira L, Mariotto A, Rowland J, Yabroff K, Alfano C . Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019; 69(5):363-385. DOI: 10.3322/caac.21565. View

17.

Fei X, Hu C, Wang X, Lu C, Chen H, Sun B . Construction of a Ferroptosis-Related Long Non-coding RNA Prognostic Signature and Competing Endogenous RNA Network in Lung Adenocarcinoma. Front Cell Dev Biol. 2021; 9:751490. PMC: 8606539. DOI: 10.3389/fcell.2021.751490. View

18.

Yang J, Hao R, Zhang Y, Deng H, Teng W, Wang Z . Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer. Cancer Cell Int. 2021; 21(1):611. PMC: 8605517. DOI: 10.1186/s12935-021-02278-z. View

19.

Wang Z, Chen S, Wang G, Li S, Qin X . CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma. Biomed Res Int. 2021; 2021:6622437. PMC: 7869413. DOI: 10.1155/2021/6622437. View

20.

Gu X, Zhang J, Ran Y, Pan H, Jia J, Zhao Y . Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression. Cell Death Dis. 2021; 12(4):356. PMC: 8024300. DOI: 10.1038/s41419-021-03626-7. View