Expression and clinical significance of annexin A2 and glycogen synthase kinase-3β  in cutaneous squamous cell carcinoma

JIANG Wen-qun HOU Pin-pin TAN Mei-le GAN Lin-quan WU Ling-yan CHENG Xian-gui

Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (3) : 294-300.

PDF(8147 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(8147 KB)
Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (3) : 294-300. DOI: 10.16098/j.issn.0529-1356.2025.03.006
Cancer Biology

Expression and clinical significance of annexin A2 and glycogen synthase kinase-3β  in cutaneous squamous cell carcinoma

  • JIANG  Wen-qun1  HOU  Pin-pin2  TAN  Mei-le3  GAN  Lin-quan3 WU  Ling-yan3  CHENG  Xian-gui3* 
Author information +
History +

Abstract

Objective To investigate the expressions of annexin A2 and glycogen synthesis kinase-3β (GSK-3β) in cutaneous squamous cell carcinoma (CSCC) tissues, and to analyze their correlation with CSCC as well as their clinical pathological diagnostic value.   Methods  The pathological tissues of 68 patients with CSCC and 40 patients with keratoacanthoma (KA) who underwent surgical treatment in the Department of Dermatology of the Second Hospital of Nanning from October 2020 to May 2024 were collected, and the surrounding normal skin tissues of 32 patients with benign skin diseases were used as controls. The expressions of annexin A2, GSK-3β and β-catenin were detected by immunohistochemistry and Western blotting. Spearman was used to evaluate the correlation between the expressions of annexin A2 and GSK-3β and the pathological characteristics in CSCC. The receiver operating characteristic (ROC) curve was drawn to analyze the clinical diagnostic value of annexin A2 and GSK-3β in CSCC.  Results Compared with the normal skin tissues, the expressions of annexin A2 and βcatenin in CSCC increased, and GSK-3β  decreased (P<0.05); Compared with the KA tissues, the expression of annexin A2 in CSCC tissues increased (P<0.05). The expression of annexin A2 was negatively correlated with that of GSK-3β in CSCC (r=-0.3901, P<0.01). GSK-3β expression was related to tissue differentiation, with lower expression in poorly differentiated patients’ cancer tissues (P<0.05). The sensitivity of annexin A2 and GSK-3β for diagnosis of CSCC was 85.3% and 41.2%, respectively, with specificities of 46.9% and 84.4% respectively. The sensitivity of annexin A2 for distinguishing between CSCC and KA was 85.3%, with a specificity of 40.0%.   Conclusion  Annexin A2 and GSK-3β may be used as potential biomarkers for the early diagnosis or differential diagnosis of CSCC, and play important roles in the development of CSCC. Their mechanism may be related to the activation of Wnt/β-catenin signaling pathway. 

Key words

 Cutaneous squamous cell carcinoma
/ Keratoacanthoma / Annexin A2 / Glycogen synthesis kinase-3β / Western blotting / Huma

Cite this article

Download Citations
JIANG Wen-qun HOU Pin-pin TAN Mei-le GAN Lin-quan WU Ling-yan CHENG Xian-gui. Expression and clinical significance of annexin A2 and glycogen synthase kinase-3β  in cutaneous squamous cell carcinoma[J]. Acta Anatomica Sinica. 2025, 56(3): 294-300 https://doi.org/10.16098/j.issn.0529-1356.2025.03.006

References

 [1] Tisack  A, Fotouhi A, Fidai C, et al. A clinical and biological review of keratoacanthoma[J]. Br J Dermatol, 2021, 185(3):487-498.
 [2] Veenstra  J, Ozog D, Loveless I, et al. Distinguishing keratoacanthoma from well-differentiated cutaneous squamous cell carcinoma using single-cell spatial pathology[J]. J Invest Dermatol, 2023, 143(12):2397-2407.e8.
 [3] Huang  Y, Jia M, Yang X, et al. Annexin A2: the diversity of pathological effects in tumorigenesis and immune response[J]. Int J Cancer, 2022, 151(4):497-509.
 [4] Domoto  T, Uehara M, Bolidong D, et al. Glycogen synthase kinase 3β in cancer biology and treatment[J]. Cells, 2020, 9(6):1388.
 [5] Skin  Cancer Research Center, Society of Dermatology and Venereology, Chinese Medical Association, Group of dermatology and oncology, division of Dermatologists, Chinese Medical Association. Consensus on diagnosis and treatment of cutaneous squamous cell carcinoma (2021) [J]. Chinese Journal of Dermatology, 2021, 54(8):653-664.  (in Chinese) 
中华医学会皮肤性病学分会皮肤肿瘤研究中心, 中国医师协会皮肤科医师分会皮肤肿瘤学组. 皮肤鳞状细胞癌诊疗专家共识(2021)[J]. 中华皮肤科杂志, 2021,54(8):653-664.
 [6] Yan  F, Tillman BN, Nijhawan RI, et al. High-Risk cutaneous squamous cell carcinoma of the head and neck: a clinical review[J]. Ann Surg Oncol, 2021, 28(13):9009-9030.
 [7] Yan  G, Li L, Zhu S, et al. Single-cell transcriptomic analysis reveals the critical molecular pattern of UV-induced cutaneous squamous cell carcinoma[J]. Cell Death Dis, 2021, 13(1):23.
 [8] Lubov  J, Labbé M, Sioufi K, et al. Prognostic factors of head and neck cutaneous squamous cell carcinoma: a systematic review[J]. J Otolaryngol Head Neck Surg, 2021, 50(1):54.
 [9] Bharadwaj  A, Kempster E, Waisman DM. The Annexin A2/S100A10 complex: the mutualistic symbiosis of two distinct proteins[J]. Biomolecules, 2021, 11(12):1849.
 [10] Li  Z, Yu L, Hu B, et al. Advances in cancer treatment: a new therapeutic target, Annexin A2[J]. J Cancer, 2021, 12(12):3587-3596.
 [11] Sun  T, Zhang J. ETV4 mediates the Wnt/β-catenin pathway through transcriptional activation of ANXA2 to promote hepatitis B virus-associated liver hepatocellular carcinoma progression[J]. J Biochem, 2021, 170(5):663-673.
 [12] Wang  Y, Wang Y, Liu W, et al. TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis[J]. Cell Death Dis, 2023, 14(2):141.
 [13] Wu  HY, Zhang F. Expressions and clinical significance of serum PD-L1 and Annexin A2 in cutaneous squamous cell carcinoma[J]. Journal of North Sichuan Medical College, 2021, 36(12):1561-1564.  (in Chinese) 
吴海严, 张帆. 皮肤鳞状细胞癌血清PD-L1、Annexin A2表达及其临床意义[J]. 川北医学院学报, 2021, 36(12):1561-1564.
 [14] Carr  RA, Mesiano D, Heffron C, et al. Aberrant p16, p53 and Ki-67 immunohistochemistry staining patterns can distinguish solitary keratoacanthoma from cutaneous squamous cell carcinoma[J]. Pathology, 2023, 55(6):772-784.
 [15] Lin  J, Song T, Li C, et al. GSK-3β in DNA repair, apoptosis, and resistance of chemotherapy, radiotherapy of cancer[J]. Biochim Biophys Acta Mol Cell Res, 2020, 1867(5):118659.
 [16] Walz  A, Ugolkov A, Chandra S, et al. Molecular pathways: revisiting glycogen synthase kinase-3β as a target for the treatment of cancer[J]. Clin Cancer Res, 2017, 23(8):1891-1897.
 [17] He R, Du S, Lei T, et al. Glycogen synthase kinase 3β in tumorigenesis and oncotherapy[J]. Oncol Rep, 2020, 44(6):2373-2385.
 [18] Zhao  LM, Zhang ShF. Expression of Axin1, GSK-3β and CD82 in cutaneous squamous cell carcinoma[J]. China Journal of Leprosy and Skin Diseases, 2020, 36(11):658-662,682.  (in Chinese) 
朝鲁门, 张士发. Axin1、GSK-3β和CD82在皮肤鳞状细胞癌中的表达[J]. 中国麻风皮肤病杂志, 2020, 36(11):658-662,682.
 [19] Law  SM, Zheng JJ. Premise and peril of Wnt signaling activation through GSK-3β inhibition[J]. iScience, 2022, 25(4):104159.
 [20] Liu  JSh, Fan B, Huang J, et al. Expression of SOX4 gene and its biological effects in endometrial carcinoma[J]. Acta Anatomica Sinica, 2021, 52(3):425-431.  (in Chinese) 
刘佳淑, 范波, 黄锦, 等. SOX4在子宫内膜癌组织中的表达及其生物学作用[J].解剖学报, 2021, 52(3):425-431.
 [21] Pan  H, Song Y, Zhang H, et al. Radiation engenders converse migration and invasion in colorectal cancer cells through opposite modulation of ANXA2/AKT/GSK3beta pathway[J]. Am J Cancer Res, 2021, 11(1):61-78.
PDF(8147 KB)

Accesses

Citation

Detail

Sections
Recommended

/