目的: 探究宫颈癌组织T细胞免疫球蛋白黏蛋白分子3（T-cell immunoglobulin mucin molecule 3,TIM-3）、唾液酸结合Ig样凝集素9（sialic acid binding Ig like lectin 9,SIGLEC9）、Yes相关蛋白1（Yes associated protein 1,YAP1）蛋白表达及与临床病理特征和预后的关系。方法: 纳入2020年7月—2022年7月潍坊市人民医院就诊宫颈癌根治术患者82例。统计癌组织与癌旁组织中TIM-3、SIGLEC9、YAP1蛋白表达情况,分析癌组织TIM-3、SIGLEC9、YAP1蛋白表达与临床病理的关系;采用Spearman等级相关分析法探究癌组织TIM-3、SIGLEC9、YAP1蛋白表达间的相关性。根据患者随访2年内生存预后情况,分为预后良好组与预后不良,对比不同生存状态患者癌组织中TIM-3、SIGLEC9、YAP1蛋白表达差异,采用Kaplan-Meier生存分析法分析癌组织TIM-3、SIGLEC9、YAP1蛋白与预后的关系。结果: TIM-3、SIGLEC9 、YAP1在癌组织中阳性表达率分别为68.29%（56/82）、60.98%（50/82）、76.83%（63/82）,在癌旁组织中阳性表达率分别为6.10%（5/82）、2.44%（2/82）、6.10%（5/82）;癌组织TIM-3、SIGLEC9、YAP1蛋白表达水平均与临床分期、分化程度、宫颈浸润深度及淋巴结转移显著相关,其中临床分期高、分化程度低、宫颈浸润深度高、淋巴结转移的患者TIM-3、SIGLEC9、YAP1蛋白阳性表达率更高;Spearman等级相关分析发现,宫颈癌患者中TIM-3阳性表达与SIGLEC9、YAP1阳性表达呈显著正相关,SIGLEC9与YAP1阳性表达呈显著正相关;预后不良组癌组织中TIM-3、SIGLEC9、YAP1蛋白阳性表达率显著高于预后良好组;TIM-3阳性组与TIM-3阴性组无进展生存期（progression-free-survival,PFS）（log rank χ2=4.846,P=0.028）、SIGLEC9阳性组与SIGLEC9阴性组PFS（log rank χ2=4.112,P=0.043）、YAP1阳性组与YAP1阴性组PFS（log rank χ2=10.011,P=0.002）差异均有统计学意义。结论: 临床分期高、分化程度低、宫颈浸润深度高、淋巴结转移的患者更易出现癌组织TIM-3、SIGLEC9、YAP1蛋白阳性表达;且该类蛋白阳性表达与不良预后具有相关性。
Abstract
Objective To investigate the protein expressions of T-cell immunoglobulin mucin molecule 3(TIM-3), sialic acid binding Ig like lectin 9 (SIGLEC9) and Yes associated protein 1 (YAP1) in cancer tissues of patients with cervical cancer and the relationship with pathological characteristics and prognosis. Methods 82 patients with radical resection of cervical cancer were enrolled in Weifang People's Hospital from July 2020 to July 2022. The protein expressions of TIM-3, SIGLEC9 and YAP1 in cancer tissues and adjacent tissues were counted, and the relationship between protein expressions of TIM-3, SIGLEC9 and YAP1 in cancer tissues and clinicopathology was analyzed. According to the survival prognosis status of patients within 2 years of follow-up, they were divided into good prognosis group and poor prognosis group. The differences in the protein expression of TIM-3, SIGLEC9 and YAP1 in cancer tissues of patients with different survival status were compared. Kaplan-Meier survival analysis was used to analyze the relationship between TIM-3, SIGLEC9, YAP1 proteins in cancer tissues and prognosis. Results The positive expressions of TIM-3 in cancer tissues and adjacent tissues were 68.29% (56/82) and 6.10% (5/82), and the positive expressions of SIGLEC9 were 60.98% (50/82) and 2.44% (2/82), and the positive expressions of YAP1 were 76.83% (63/82) and 6.10% (5/82). The protein expression levels of TIM-3, SIGLEC9 and YAP1 in cancer tissues were significantly correlated with clinical staging, differentiation degree, depth of cervical invasion and lymph node metastasis. The positive expression rates of TIM-3, SIGLEC9 and YAP1 proteins in patients with high clinical stage, low differentiation degree, high depth of cervical invasion and lymph node metastasis were higher. The positive expression rates of TIM-3, SIGLEC9 and YAP1 proteins in poor prognosis group were significantly higher than those in good prognosis group. The progression-free-survival (PFS) in TIM-3 positive group was statistically different from TIM-3 negative group (log rank χ2=4.846, P=0.028). The PFS was statistically different between SIGLEC9 positive group and SIGLEC9 negative group (log rank χ2=4.112, P=0.043). The PFS of YAP1 in positive group and YAP1 negative group was statistically different (log rank χ2=10.011, P=0.002). Conclusion Patients with high clinical stage, low degree of differentiation, high depth of cervical invasion and lymph node metastasis are more likely to have positive protein expressions of TIM-3, SIGLEC9 and YAP1 in cancer tissues, and the positive expressions of the above proteins are related to poor prognosis.
关键词
宫颈癌 /
T细胞免疫球蛋白黏蛋白分子3 /
唾液酸结合Ig样凝集素9 /
Yes相关蛋白1 /
病理特征 /
预后分析
Key words
cervical cancer /
T-cell immunoglobulin mucin molecule 3 /
sialic acid binding Ig like lectin 9 /
Yes associated protein 1 /
pathological characteristics /
prognostic analysis
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参考文献
[1] 赵晓化, 李维艳, 夏燕, 等. 血清PDCD4、HSP70水平对早期宫颈癌淋巴结转移的预测价值[J]. 山东医药, 2024, 64(28): 27-31.
[2] 陈晨, 罗冬梅, 顾晓芬. 中生对宫颈癌、HPV及HPV疫苗认知现状及影响因素分析[J]. 职业与健康, 2023, 39(4): 525-530.
[3] 于鹃鹏, 秦珊珊, 郁胜胜, 等. 腹腔镜下子宫深静脉入路C型宫颈癌根治术的疗效[J]. 中国微创外科杂志 (中英文), 2024, 24(1): 45-49.
[4] YU L, LANQING G, HUANG Z, et al.T cell immunotherapy for cervical cancer: challenges and opportunities[J]. Front Immunol, 2023, 14(1): 1-12.
[5] HIRAHARA Y, SHIMIZU K, YAMASAKI S, et al.Crucial immunological roles of the invasion front in innate and adaptive immunity in cervical cancer[J]. Br J Cancer, 2024, 131(11): 1762-1774.
[6] ZHAO F, TIAN H, WANG Y, et al.LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma[J]. Cancer Immunol Immunother, 2023, 72(6): 1835-1851.
[7] ZHANG J, CHEN B, LI H, et al.Cancer-associated fibroblasts potentiate colorectal cancer progression by crosstalk of the IGF2-IGF1R and Hippo-YAP1 signaling pathways[J]. J Pathol, 2023, 259(2): 205-219.
[8] 中国抗癌协会妇科肿瘤专业委员会. 子宫颈癌诊断与治疗指南 (2021年版)[J]. 中国癌症杂志, 2021, 31(6): 474-489.
[9] 吴玲芳. 鹰潭市余江区老年女性宫颈癌防治知识知晓情况及与患病的相关性分析[J]. 感染、炎症、修复, 2023, 24(2): 99-101.
[10] 陈秀敏, 吴熊军, 许文彬, 等. T细胞免疫球蛋白黏蛋白分子3对宫颈癌细胞生物学行为及肿瘤免疫微环境的影响[J]. 中国免疫学杂志, 2023, 39(11): 2282-2287, 2293.
[11] 闫璐, 张金辉, 李维玲, 等. miR-330、Tim-3基因表达与宫颈癌患者临床病理参数及预后的关系[J]. 山东医药, 2024, 64(19): 76-79.
[12] ZEIDAN AM, KOMROKJI RS, BRUNNER AM.TIM-3 pathway dysregulation and targeting in cancer[J]. Expert Rev Anticancer Ther, 2021, 21(5): 523-534.
[13] DIXON KO, TABAKA M, SCHRAMM MA, et al.TIM-3 restrains anti-tumour immunity by regulating inflammasome activation[J]. Nature, 2021, 595(7865): 101-106.
[14] 王碧辉, 朱玥洁, 张玉莲, 等. 新型免疫检查点SIGLEC9在宫颈癌中的表达及临床相关性分析[J]. 中国肿瘤临床, 2024, 51(4): 178-185.
[15] MEI Y, WANG X, ZHANG J, et al.Siglec-9 acts as an immune-checkpoint molecule on macrophages in glioblastoma, restricting T-cell priming and immunotherapy response[J]. Nat Cancer, 2023, 4(9): 1273-1291.
[16] ZHAO F, TIAN H, WANG Y, et al.LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma[J]. Cancer Immunol Immunother, 2023, 72(6): 1835-1851.
[17] SZULZEWSKY F, HOLLAND EC, VASIOUKHIN V.YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance[J]. Dev Biol, 2021, 475(1): 205-221.
[18] WANG T, WANG D, SUN Y, et al.Regulation of the Hippo/YAP axis by CXCR7 in the tumorigenesis of gastric cancer[J]. J Exp Clin Cancer Res, 2023, 42(1): 297-319.
[19] GOENKA A, KHAN F, VERMA B, et al.Tumor microenvironment signaling and therapeutics in cancer progression[J]. Cancer Commun (Lond), 2023, 43(5): 525-561.
[20] SIM J, PARK J, KIM S, et al.Association of Tim-3/Gal-9 Axis with NLRC4 Inflammasome in Glioma Malignancy: Tim-3/Gal-9 Induce the NL1RC4 Inflammasome[J]. Int J Mol Sci, 2022, 23(4): 2028-2045.
基金
山东省医务职工科技创新计划项目“利用单细胞基因组学和单细胞染色质结构技术研究知母皂苷对骨肉瘤化疗药物甲氨蝶呤敏感性的增敏机制”（SDYWZGKCJHLH2023063）
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