Objective　To investigate the expression, diagnostic efficacy, and clinical significance of α1-antichymotrypsin (AACT) encoded by SERPINA3 in prostate cancer (PCa).

Methods　Publicly-available database analysis evaluated SERPINA3 expression and its correlation with clinical features. Serum samples from treatment-naïve PCa patients, benign prostatic hyperplasia (BPH) patients and healthy controls collected at Zhongnan Hospital of Wuhan University were analyzed via ELISA for AACT expression levels. The receiver operating characteristic curve and its area under the curve (AUC) were assessed for diagnostic performance. ssGSEA analyzed associations between SERPINA3 expression and pro-oncogenic pathways using TCGA data.

Results　SERPINA3 expression was significantly elevated in PCa patients versus controls (P < 0.05). ELISA revealed higher serum AACT levels in PCa compared to BPH patients (P < 0.001). The AUC value of distinguishing PCa from BPH and healthy control was 0.968 ［95%CI (0.930, 0.998)］ and 0.958 ［95%CI (0.910, 0.994)］, respectively. ssGSEA demonstrated strong correlations between SERPINA3 and pro-tumor pathways (apoptosis, DNA repair, metabolism) (P < 0.001).

Conclusion　Serum AACT exhibits high clinical potential for early PC diagnosis.

1.Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263.

2.Bergengren O, Pekala KR, Matsoukas K, et al. 2022 update on prostate cancer epidemiology and risk factors-a systematic review[J]. Eur Urol, 2023, 84(2): 191-206.

3.Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33.

4.Qi J, Li M, Wang L, et al. National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data[J]. Lancet Public Health, 2023, 8(12): e943-e955.

5.邓通, 蔡林, 陈征, 等. 1990年与2017年中国前列腺癌疾病负担分析[J]. 医学新知, 2020, 30(4): 252-259.[Deng T, Cai L, Chen Z, et al. Analysis of prostate cancer disease burden in China from 1990 to 2017[J]. Yixue Xinzhi Zazhi, 2020, 30(4): 252-259.]

6.Li X, Li C, Chen M. Patients with "gray zone" PSA levels: application of prostate MRI and MRS in the diagnosis of prostate cancer[J]. J Magn Reson Imaging, 2023, 57(4): 992-1010.

7.Xie H, Fan J, Wang J, et al. Serological proteomic profiling uncovered CDK5RAP2 as a novel marker in benign prostatic hyperplasia[J]. Clin Biochem, 2025, 135: 110867.

8.Soman SA. Unfolding the cascade of SERPINA3: inflammation to cancer[J]. Biochim Biophys Acta Rev Can-cerhttps://pubmed.ncbi.nlm.nih.gov/35843512/, 2022, 1878(3): 188874.

9.de Mezer M, Rogalinski J, Przewozny S, et al. SERPINA3: stimulator or inhibitor of pathological changes[J]. Biomedicines, 2023, 11(1): 180.

10.Zhang Y, Tian J, Qu C, et al. Overexpression of SERPINA3 promotes tumor invasion and migration, epitheli-al-mesenchymal-transition in triple-negative breast cancer cells[J]. Breast Cancer, 2021, 28(4):859-873.

11.Soman A, Pradhan T, Krishna R, et al. Decoding early-onset of colorectal cancer: insights into SERPINA3 expression patterns[J]. Heliyon, 2024, 10(22): e40119.

12.Sekhoacha M, Riet K, Motloung P, et al. Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches[J]. Molecules, 2022, 27(17): 5730.

13.Chen H, Xu C, Fang Z, et al. Cell-free DNA, microRNAs, Proteins, and peptides as liquid biopsy biomarkers in prostate cancer and bladder cancer[J]. Methods Mol Biol, 2023, 2695: 165-179.

14.Lopez-Campos F, Linares-Espinosa E, Maldonado PX, et al. Genetic testing for the clinician in prostate cancer[J]. Expert Rev Mol Diagn, 2020, 20(9): 933-946.

15.Wu J, Yang Z, Ding J, et al. Proteome-wide Mendelian randomization identifies causal plasma proteins in prostate cancer development[J]. Hum Genomics, 2025, 19(1): 17.

16.Jin Y, Wang W, Wang Q, et al. Alpha-1-antichymotrypsin as a novel biomarker for diagnosis, prognosis, and therapy prediction in human diseases[J]. Cancer Cell Int, 2022, 22(1): 156.

17.Xing Z, Li S, Liu Z, et al. CircSERPINA3 regulates SERPINA3-mediated apoptosis, autophagy and aerobic glycolysis of prostate cancer cells by competitively binding to MiR-653-5p and recruiting BUD13[J]. J Transl Med, 2021, 19(1): 492.

18.Xie J, Chen Q, Li L, et al. Overexpression of SERPINA3 inhibits castration-resistant prostate cancer progression via M1 macrophage[J]. Braz J Med Biol Res, 2025, 58(3): e14124.

19.Camandona A, Gagliardi A, Licheri N, et al. Multiple regulatory events contribute to a widespread circular RNA downregulation in precancer and early stage of colorectal cancer development[J]. Biomark Res, 2025, 13(1): 22.

20.Ito K, Yamamoto T, Hayashi Y, et al. Osteoblast-derived extracellular vesicles exert osteoblastic and tumor-suppressive functions via SERPINA3 and LCN2 in prostate cancer[J]. Mol Oncol, 2023, 17(10): 2147-2167.