Advanced Search
YANG Peng, QIU Ziyi, WANG Lingling, HU Yuan, CHEN Zhengzhen, ZHONG Meizhen, YU Feiyue, QIU Rongyuan. Effect of CCNA2 on Prognosis of Colon Cancer by Regulating Immune Microenvironment of Tumor Cells[J]. Cancer Research on Prevention and Treatment, 2025, 52(4): 305-312. DOI: 10.3971/j.issn.1000-8578.2025.24.0947
Citation: YANG Peng, QIU Ziyi, WANG Lingling, HU Yuan, CHEN Zhengzhen, ZHONG Meizhen, YU Feiyue, QIU Rongyuan. Effect of CCNA2 on Prognosis of Colon Cancer by Regulating Immune Microenvironment of Tumor Cells[J]. Cancer Research on Prevention and Treatment, 2025, 52(4): 305-312. DOI: 10.3971/j.issn.1000-8578.2025.24.0947

Effect of CCNA2 on Prognosis of Colon Cancer by Regulating Immune Microenvironment of Tumor Cells

More Information
  • Corresponding author:

    QIU Rongyuan, E-mail: 277563770@qq.com

  • Received Date: September 24, 2024
  • Revised Date: December 19, 2024
  • Accepted Date: January 12, 2025
  • Available Online: February 19, 2025
  • Objective 

    To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration.

    Methods 

    We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer.

    Results 

    Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low.

    Conclusion 

    CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

  • Competing interests: The authors declare that they have no competing interests.

  • [1]
    Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024[J]. CA Cancer J Clin, 2024, 74(1): 12-49. doi: 10.3322/caac.21820
    [2]
    Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
    [3]
    Siegel RL, Torre LA, Soerjomataram I, et al. Global patterns and trends in colorectal cancer incidence in young adults[J]. Gut, 2019, 68(12): 2179-2185. doi: 10.1136/gutjnl-2019-319511
    [4]
    Loukil A, Cheung CT, Bendris N, et al. Cyclin A2: At the crossroads of cell cycle and cell invasion[J]. World J Biol Chem, 2015, 6(4): 346-350.
    [5]
    Zhang QH, Yuen WS, Adhikari D, et al. Cyclin A2 modulates kinetochore-microtubule attachment in meiosis Ⅱ[J]. J Cell Biol, 2017, 216(10): 3133-3143.
    [6]
    Chen S, Zhao Z, Wang X, et al. The Predictive Competing Endogenous RNA Regulatory Networks and Potential Prognostic and Immunological Roles of Cyclin A2 in Pan-Cancer Analysis[J]. Front Mol Biosci, 2022, 9: 809509. doi: 10.3389/fmolb.2022.809509
    [7]
    Blanchard JM. Cyclin A2 transcriptional regulation: modulation of cell cycle control at the G1/S transition by peripheral cues[J]. Biochem Pharmacol, 2000, 60(8): 1179-1184.
    [8]
    Hydbring P, Malumbres M, Sicinski P. Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases[J]. Nat Rev Mol Cell Biol, 2016, 17(5): 280-292. doi: 10.1038/nrm.2016.27
    [9]
    Jiang A, Zhou Y, Gong W, et al. CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types[J]. Oxid Med Cell Longev, 2022, 2022: 5910575.
    [10]
    Wu SQ, Huang SH, Lin QW, et al. FDI-6 and olaparib synergistically inhibit the growth of pancreatic cancer by repressing BUB1, BRCA1 and CDC25A signaling pathways[J]. Pharmacol Res, 2022, 175: 106040.
    [11]
    Liu X, Liu X, Qiao T, et al. Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis[J]. Oncol Lett, 2020, 19(3): 1881-1889.
    [12]
    González-Mariscal L, Miranda J, Gallego-Gutiérrez H, et al. Relationship between apical junction proteins, gene expression and cancer[J]. Biochim Biophys Acta Biomembr, 2020, 1862(9): 183278. doi: 10.1016/j.bbamem.2020.183278
    [13]
    Jiang J. Hedgehog signaling mechanism and role in cancer[J]. Semin Cancer Biol, 2022, 85: 107-122. doi: 10.1016/j.semcancer.2021.04.003
    [14]
    Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2014, 15(3): 178-196. doi: 10.1038/nrm3758
    [15]
    Liu J, Xiao Q, Xiao J, et al. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities[J]. Signal Transduct Target Ther, 2022, 7(1): 3. doi: 10.1038/s41392-021-00762-6
    [16]
    Pai SG, Carneiro BA, Mota JM, et al. Wnt/beta-catenin pathway: modulating anticancer immune response[J]. J Hematol Oncol, 2017, 10(1): 101. doi: 10.1186/s13045-017-0471-6
    [17]
    Kim SI, Park CS, Lee MS, et al. Cyclin-dependent kinase 2 regulates the interaction of Axin with beta-catenin[J]. Biochem Biophys Res Commun, 2004, 317(2): 478-483. doi: 10.1016/j.bbrc.2004.03.065
    [18]
    Guo Y, Gabola M, Lattanzio R, et al. Cyclin A2 maintains colon homeostasis and is a prognostic factor in colorectal cancer[J]. J Clin Invest, 2021, 131(4): e131517. doi: 10.1172/JCI131517
    [19]
    Dias Carvalho P, Guimarães CF, Cardoso AP, et al. KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment[J]. Cancer Res, 2018, 78(1): 7-14. doi: 10.1158/0008-5472.CAN-17-2084
    [20]
    Yan Y, Huang L, Liu Y, et al. Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity[J]. J Hematol Oncol, 2022, 15(1): 104. doi: 10.1186/s13045-022-01322-3
    [21]
    Liu J, Huang X, Liu H, et al. Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients[J]. J Transl Med, 2021, 19(1): 27. doi: 10.1186/s12967-020-02638-9
    [22]
    Zdanov S, Mandapathil M, Abu Eid R, et al. Mutant KRAS Conversion of Conventional T Cells into Regulatory T Cells[J]. Cancer Immunol Res, 2016, 4(4): 354-365. doi: 10.1158/2326-6066.CIR-15-0241
    [23]
    Ji L, Qian W, Gui L, et al. Blockade of β-Catenin-Induced CCL28 Suppresses Gastric Cancer Progression via Inhibition of Treg Cell Infiltration[J]. Cancer Res, 2020, 80(10): 2004-2016. doi: 10.1158/0008-5472.CAN-19-3074
    [24]
    Miao X, Leng X, Zhang Q. The Current State of Nanoparticle-Induced Macrophage Polarization and Reprogramming Research[J]. Int J Mol Sci, 2017, 18(2): 336. doi: 10.3390/ijms18020336
    [25]
    Zhang S, Tischer T, Barford D. Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C[J]. Nat Commun, 2019, 10(1): 3863. doi: 10.1038/s41467-019-11833-2

Catalog

    Figures(8)  /  Tables(1)

    Article views (1156) PDF downloads (165) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return