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张怡然, 邓丹, 尹万, 等. 结直肠癌根治术后患者Tim-3、galectin-9表达水平与其临床病理特征及预后的关系[J]. koko体育app 学报(医学版), 2024, 55(2): 375-382. DOI:
引用本文: 张怡然, 邓丹, 尹万, 等. 结直肠癌根治术后患者Tim-3、galectin-9表达水平与其临床病理特征及预后的关系[J]. koko体育app 学报(医学版), 2024, 55(2): 375-382. DOI:
ZHANG Yiran, DENG Dan, YIN Wan, et al. Relationship Between Tim-3 and Galectin-9 Expression Levels, Clinical Pathological Characteristics, and Prognosis in Patients After Radical Resection of Colorectal Cancer[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(2): 375-382. DOI:
Citation: ZHANG Yiran, DENG Dan, YIN Wan, et al. Relationship Between Tim-3 and Galectin-9 Expression Levels,ಞ Clinical Pathological Characteristics, and Prognosis in Patients After Radical Resection of C🍌olorectal Cancer[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(2): 375-382. DOI:

结直肠癌根治术后患者Tim-3、galectin-9表达水平与其临床病理特征及预后的关系

Relationship Between Tim-3 and Galectin-9 Expression Levels, Clinical Pathological Characteristics, and Prognosis in Patients After Radical Resection of Colorectal Cancer

  • 摘要:
    目的  结直肠癌经根治术治疗后仍有部分患者易复发且预后较差,因此,寻找结直肠癌根治术患者预后判断的潜在生化标志物和药物靶点,对于优化此类群体临床结局具有积极意义。近年来新发现T细胞免疫球蛋白及黏蛋白结构域分子3(T cell immunoglobulin and mucin domain protein 3, Tim-3)及其配体半乳糖凝集素9(galactose lectin 9, galectin-9)在包括结直肠癌等多种肿瘤引起的免疫功能障碍中扮演着关键角色,但是其在结直肠癌中的表达、生物学作用与预后的价值尚不明确,故而本文旨在探究结直肠癌根治术患者Tim-3、galectin-9表达水平与其临床病理特征及预后的关系。
    方法  选择2018年2月–2019年3月于成都市第五人民医院进行结直肠癌根治术治疗患者171例,采用免疫组化测定患者癌组织样本及癌旁组织中Tim-3、galectin-9的表达情况,并分析其与患者基线参数的关系。利用Kaplan-Meier法分析Tim-3、galectin-9与结直肠癌患者无复发生存期(relapse-free survival, RFS)和总生存期(overall survival, OS)的关系,Cox回归分析影响患者预后不良因素。
    结果  免疫组化结果显示,结直肠癌组织中Tim-3、galectin-9的高表达率分别为70.18%(120/171)、32.16%(55/171),而低表达率分别为29.82%(51/171)、67.84%(116/171)。同时,结直肠癌组织Tim-3的表达评分相较于配对癌旁组织偏高,而galectin-9的表达评分则偏低(P<0.05);进一步分析发现,Tim-3、galectin-9表达与浸润深度、脉管浸润、临床分期均有关(P<0.05)。随访14~63个月,171例结直肠癌患者中有7例失访,剩余患者组织中Tim-3、galectin-9表达呈现异常低表达的患者分别为49、112例,高表达患者分别为115、52例,Kaplan-Meier生存分析显示,结直肠癌组织中Tim-3高表达者的RFS和OS均低于低表达者,差异有统计学意义(RFS:log-rank=22.66,P<0.001;OS:log-rank=19.71,P<0.001),而galectin-9低表达者的RFS和OS则低于高表达者,差异有统计学意义(RFS:log-rank=19.45,P<0.001;OS:log-rank=22.24,P<0.001)。Cox多因素分析表明,TNM分期Ⅲ期〔风险比(hazards ratio, HR)=2.26,95%置信区间(confidence interval, CI):1.20~5.68〕以及Tim-3高表达(HR=0.80,95%CI:0.33~0.91)、galectin-9低表达(HR=1.80,95%CI:1.33~4.70)均为影响患者RFS和OS的独立危险因素(P<0.05)。
    结论  结直肠癌组织中Tim-3、galectin-9呈现异常表达,其中高表达Tim-3、低表达galectin-9与不良临床病理特征及预后关系紧密,是患者不良预后事件的独立影响因素,有望成为新的治疗靶点和临床指标。
     
    Abstract:
    Objective  Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer.
    Methods  A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients.
    Results The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues (P<0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging (P<0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P<0.001; OS: log-rank=19.71, P<0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P<0.001; OS: log-rank=22.24, P<0.001). Cox multivariate analysis indicated that TNM stage Ⅲ (HR=2.26, 95% CI: 1.20-5.68), high expression of Tim-3 (HR=0.80, 95% CI: 0.33-0.91), and low expression of galectin-9 (HR=1.80, 95% CI: 1.33-4.70) were independent risk factors affecting RFS and OS in patients (P<0.05).
    Conclusion  Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.
     
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