胆囊癌组织肿瘤抑制蛋白Tp53和NLRP3水平变化及其对术后肿瘤复发或转移的影响*

doi:10.3969/j.issn.1672-5069.2025.06.038

摘要/Abstract

摘要： 目的分析胆囊癌组织肿瘤抑制蛋白(Tp53)和核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)水平变化及其对术后肿瘤复发或转移的影响。方法 2020年1月～2024年1月我院诊治的60例胆囊癌患者和50例胆石症患者,均接受胆囊切除术,随访2年。术后取组织,采用实时荧光定量PCR法检测组织Tp53和NLRP3 mRNA水平。应用多因素Logistic回归分析影响肿瘤复发或转移的因素。结果胆囊癌组织Tp53和NLRP3 mRNA水平分别为(1.2±0.2)和(1.0±0.2),均显著高于胆囊炎组织【分别为(0.8±0.2)和(0.6±0.1),P<0.05】;在术后随访2年末,本组胆囊癌患者术后发生肿瘤复发或转移17例(28.3%);发生转移的肿瘤患者癌组织Tp53和NLRP3 mRNA水平分别为(1.4±0.3)和(1.2±0.2),均显著高于未发生肿瘤转移患者【分别为(0.9±0.1)和(0.7±0.1),P<0.05】;Logistic回归分析显示,癌组织Tp53(OR=3.554)和NLRP3(OR=3.155)高水平均是影响胆囊癌患者术后复发或转移的危险因素(P<0.05)。结论胆囊癌组织Tp53和NLRP3高水平可能预示肿瘤恶性程度高,术后容易复发或转移,需加强随访和处理。

关键词: 胆囊癌, 胆囊切除术, 肿瘤抑制蛋白p53, 核苷酸结合寡聚化结构域样受体蛋白3, 转移

Abstract: Objective The aim of this study was to explore the hepatic tumor suppressor protein (Tp53) and nucleotide binding oligomeric domain like receptor protein 3 (NLRP3) levels in patients with gallbladder cancer and their impact on tumor metastasis after surgical resection. Methods 60 patients with gallbladder cancer and 50 patients with cholecystitis were encountered in our hospital between January 2020 and January 2024, and all underwent cholecystectomy. Patients with gallbladder cancer were followed-up for 2 years. Hepatic Tp53 and NLRP3 mRNA were detected by PCR. Multivariate Logistic regression analysis was applied to find impacting factors. Results Tp53 and NLRP3 mRNA in cancerous tissues were (1.2±0.2) and (1.0±0.2), both much higher than [(0.8±0.2) and (0.6±0.1), respectively, P<0.05] in gallbladder tissues; by end of two-year follow-up after operation, tumor relapse or remote metastasis was found in 17 cases(28.3%); tumor Tp53 and NLRP3 mRNA level in patients with metastasis were (1.4±0.3) and (1.2±0.2), both significantly higher than [(0.9±0.1) and (0.7±0.1), respectively, P<0.05] in those without tumor metastasis; multivariate Logistic regression analysis showed that high levels of tumor tissue Tp53(OR=3.554) and NLRP3(OR=3.155) were both the independent risk factors for tumor relapse or remote metastasis (P<0.05). Conclusion High tumor tissue Tp53 and NLRP3 levels might hint susceptibility of tumor relapse or remote metastasis after operation in patients with gallbladder cancer, which needs further investigation.

Key words: Gallbladder cancer, Cholecystectomy, Tumor suppressor protein 53, Nucleotide binding oligomerization domain like receptor protein 3, Metastasis

朱海燕, 徐杰, 刘晓岗, 张银超, 戴敏. 胆囊癌组织肿瘤抑制蛋白Tp53和NLRP3水平变化及其对术后肿瘤复发或转移的影响^*[J]. 实用肝脏病杂志, 2025, 28(6): 950-953.

Zhu Haiyan, Xu Jie, Liu Xiaogang, et al. Hepatic tumor suppressor proteins Tp53 and NLRP3 levels in patients with gallbladder cancer and their impact on tumor metastasis after surgical resection[J]. Journal of Practical Hepatology, 2025, 28(6): 950-953.

参考文献

[1] Shi Y, Sun L, Zhang R, et al. Thrombospondin 4/integrin α2/HSF1 axis promotes proliferation and cancer stem-like traits of gallbladder cancer by enhancing reciprocal crosstalk between cancer-associated fibroblasts and tumor cells. J Exp Clin Cancer Res, 2021, 40(1): 14.
[2] Asai T, Tsuchiya Y, Mishra K, et al. Carcinogen metabolism pathway and tumor suppressor gene polymorphisms and gallbladder cancer risk in north indians: A Hospital-Based Case-Control Study. Asian Pac J Cancer Prev, 2019, 20(12): 3643-3647.
[3] 李卫峰, 张景丽, 陆中萃. 胆囊癌、胆囊腺瘤性息肉和慢性胆囊炎组织中p53、β-catenin基因的表达及临床意义. 临床和实验医学杂志, 2018, 17(4): 391-394.
[4] Zhu Z, Zhu Q, Cai D, et al. Golgi phosphoprotein 3 promotes the proliferation of gallbladder carcinoma cells via regulation of the NLRP3 inflammasome. Oncol Rep, 2021, 45(6): 113.
[5] Yamashita S, Takasu C, Morine Y, et al. Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation. J Hepatobiliary Pancreat Sci, 2023, 30(4): 462-472.
[6] 中华医学会外科学分会胆道外科学组, 中国医师协会外科医师分会胆道外科专业委员会.胆囊癌诊断和治疗指南(2019年版). 中华外科杂志, 2020, 58(4): 243-251.
[7] 汤磊, 邹桂舟. 外科疾病导致的胆源性肝损伤诊治现状. 实用肝脏病杂志, 2021, 24(6):769-771.
[8] 李嘉, 蒋基令, 黄梦黎, 等. 胆囊癌患者血清sVEGF-C和CEA水平变化及其与组织病理学特征的关系探讨. 实用肝脏病杂志, 2020, 23(2):284-287.
[9] Velez MG, Kosiorek HE, Egan JB, et al. Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis, 2022, 25(3): 479-483.
[10] Isakova JT, Vinnikov D, Kipen VN, et al. Gene-to-gene interactions and the association of TP53, XRCC1, TNFα, HMMR, MDM2 and PALB2 with breast cancer in Kyrgyz females. Breast Cancer, 2020, 27(5): 938-946.
[11] Ghavifekr Fakhr M, Rezaie Kahkhaie K, Shanehbandi D, et al. Scrophularia atropatana extract reverses TP53 gene promoter hypermethylation and decreases survivin antiapoptotic gene expression in breast cancer cells. AsianPac J cancer prev, 2018, 19(9): 2599-2605.
[12] Cardoso YMN, Resque RL, Yoshio D, et al. Association between the arg72Pro genotypes in the TP53 Gene and ile655Val in the HER2 gene and the risk of developing breast cancer in the population of amapá, northern brazil. Asian Pac J Cancer Prev, 2023, 24(1): 157-162.
[13] Ishak G, Leal MF, Dos Santos NP, et al. Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas. Clin Exp Med, 2015, 15(3):421-426.
[14] Tang X, Pan L, Zhao S, et al. SNO-MLP (S-nitrosylation of muscle LIM protein) facilitates myocardial hypertrophy through TLR3 (Toll-like receptor 3)-mediated RIP3 (receptor-interacting protein kinase 3) and NLRP3 (NOD-like receptor pyrin domain containing 3) inflammasome activation. Circulation, 2020, 141(12): 984-1000.
[15] Tang YL, Tao Y, Zhu L, et al. Role of NLRP3 inflammasome in hepatocellular carcinoma: A double-edged sword. Int Immunopharmacol, 2023, 118:110107.
[16] Gordon M, Meagher P, Connelly KA. Effect of empagliflozin and liraglutide on the nucleotide-binding andoligomerization domain-like receptor family pyrin domain-containing 3 inflammasome in a rodent nodel of type 2 diabetes mellitus. Can J Diabetes, 2021, 45(6): 553-556.
[17] Wang B, Yang X, Zuo X, et al. Oxidative stress initiates receptor-interacting protein kinase-3/mixed lineage kinase domain-Like-mediated corneal epithelialnecroptosis and nucleotide-binding oligomerization domain-like rReceptor protein 3 inflammasome signaling during fungal keratitis. Am J Pathol, 2023, 193(7): 883-898.
[18] 邹吉, 陈晓波, 董仁华, 等. 胆囊切除联合肝组织楔形切除和区域淋巴结清扫治疗胆囊癌患者疗效研究. 实用肝脏病杂志, 2022, 25(4):599-602.
[19] Rajput M, Chigurupati S, Purwar R, et al. MAP kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: results from bioinformatic analysis of next generation sequencing data from a hospital-based cohort (NCT05404347). Mol Biol Rep, 2022, 49(11): 10153-10163.
[20] Kawakami S, Takano S, Fukasawa M, et al. Stepwise correlation of TP53 mutations from pancreaticobiliary maljunction to gallbladder carcinoma: a retrospective study. BMC Cancer, 2021, 21(1):1245.

胆囊癌组织肿瘤抑制蛋白Tp53和NLRP3水平变化及其对术后肿瘤复发或转移的影响^*

Hepatic tumor suppressor proteins Tp53 and NLRP3 levels in patients with gallbladder cancer and their impact on tumor metastasis after surgical resection

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