目的: 检测并比较超重/肥胖结直肠癌患者和健康体检人员血清中转录激活因子3(ATF3)的表达差异,探究ATF3与超重/肥胖结直肠恶性肿瘤的临床病理相关性及其诊断效能,评估其作为超重/肥胖结直肠癌患者早期诊断的分子标志物的价值。方法: 使用酶联免疫吸附试验检测34例结直肠癌患者和24例健康体检人员血清中ATF3的表达水平,分析其表达水平与结直肠癌临床病理特征的关系。利用 ROC 曲线评估ATF3的诊断效能,并与临床常用肿瘤标志物癌胚抗原进行比较,评估其作为分子标志物在诊断超重/肥胖人群结直肠癌方面的临床价值。结果: 正常体质量结直肠癌患者和健康体检人员的血清ATF3表达水平差异无统计学意义(P＞0.05),超重/肥胖结直肠癌患者血清ATF3的表达水平明显高于超重/肥胖健康体检人员 (P＜<0.05)。超重/肥胖结直肠癌患者血清ATF3表达水平与肿瘤部位和TNM分期密切相关。ROC曲线结果表明ATF3对超重/肥胖结直肠癌患者的诊断效能高于临床常用肿瘤标志物癌胚抗原。结论: 超重/肥胖结直肠癌患者血清中ATF3的表达水平升高,与结直肠癌的恶性进展密切相关。ATF3具有成为超重/肥胖人群结直肠癌分子诊断的血清学指标的潜力。
Objective: To explore the clinicopathological correlation between transcriptional activator factor 3 (ATF3) and overweight/obese patients with colorectal cancer (CRC) and its diagnostic efficacy, and to assess its value of being molecular marker for early diagnosis of CRC by detecting its expression levels in the serum of overweight/obese colorectal cancer patients and healthy physical examiners. Methods: The expression levels of ATF3 in the serum of 34 colorectal cancer patients and 24 healthy physical participants were detected using enzyme-linked immunosorbent assay (ELISA), and the relation＜between ATF3 expression levels and the clinicopathological features of CRC was analyzed. The diagnostic efficacy of ATF3 was assessed using ROC curves and compared with the commonly used carcinoembryonic antigen to evaluate its clinical value of being a molecular marker in the diagnosis of CRC in overweight/obese people. Results: There was no significant difference in the expression levels of serum ATF3 between normal weight CRC patients and healthy participants, and the expression levels of serum ATF3 in overweight/obese CRC patients were significantly higher than those in overweight/obese healthy participants (P＜0.05). The ROC curves showed that the diagnostic efficacy of ATF3 in overweight/obese CRC patients was higher than that of the commonly used carcinoembryonic antigen. Conclusion: The elevated expression level of ATF3 in the serum of overweight/obese CRC patients is closely related to the progression of colorectal cancer. ATF3 is potential to become a serological indicator for the molecular diagnosis of CRC in overweight/obese population.
[1] 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.
[2] Chen YX, Liu C, Zhu SM, et al. PD-1/PD-L1 immune checkpoint blockade-based combinational treatment: immunotherapeutic amplification strategies against colorectal cancer[J]. Int Immunopharmacol, 2021, 96: 107607.
[3] Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer[J]. Lancet, 2019, 394(10207): 1467-1480.
[4] Wang B, Yang X, Sun X, et al. ATF3 in atherosclerosis: a controversial transcription factor[J]. J Mol Med (Berl), 2022, 100(11): 1557-1568.
[5] Wu XW, Nguyen BC, Dziunycz P, et al. Opposing roles for calcineurin and ATF3 in squamous skin cancer[J]. Nature, 2010, 465(7296): 368-372.
[6] Ku HC, Cheng CF. Master regulator activating transcription factor 3 (ATF3) in metabolic homeostasis and cancer[J]. Front Endocrinol, 2020, 11: 556.
[7] Chen ML, Liu YJ, Yang YQ, et al. Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: implications in cancer immunotherapy[J]. Genes Dis, 2021, 9(4): 981-999.
[8] Kim S, Song NJ, Bahn G, et al. Atf3 induction is a therapeutic target for obesity and metabolic diseases[J]. Biochem Biophys Res Commun, 2018, 504(4): 903-908.
[9] Ku HC, Chan TY, Chung JF, et al. The ATF3 inducer protects against diet-induced obesity via suppressing adipocyte adipogenesis and promoting lipolysis and browning[J]. Biomed Pharmacother, 2022, 145: 112440.
[10] Zygulska AL, Pierzchalski P. Novel diagnostic biomarkers in colorectal cancer[J]. Int J Mol Sci, 2022, 23(2): 852.
[11] Yan F, Ying L, Li XF, et al. Overexpression of the transcription factor ATF3 with a regulatory molecular signature associates with the pathogenic development of colorectal cancer[J]. Oncotarget, 2017, 8(29): 47020-47036.
[12] Hackl C, Lang SA, Moser C, et al. Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition[J]. BMC Cancer, 2010, 10: 668.
[13] Wu ZY, Wei ZM, Sun SJ, et al. Activating transcription factor 3 promotes colon cancer metastasis[J]. Tumour Biol, 2014, 35(8): 8329-8334.
[14] Jang MK, Jung MH. ATF3 represses PPARγ expression and inhibits adipocyte differentiation[J]. Biochem Biophys Res Commun, 2014, 454(1): 58-64.
[15] Jang MK, Son Y, Jung MH. ATF3 plays a role in adipocyte hypoxia-mediated mitochondria dysfunction in obesity[J]. Biochem Biophys Res Commun, 2013, 431(3): 421-427.
[16] Zhu HJ, Liu MJ, Zhang NR, et al. Serum and adipose tissue mRNA levels of ATF3 and FNDC5/irisin in colorectal cancer patients with or without obesity[J]. Front Physiol, 2018, 9: 1125.
