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Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
摘要：
■一些结直肠癌患者即使在接受了根治性切除术的手术治疗后仍面临高复发率和不良预后。确定潜在的生化标志物和治疗靶标，以评估接受结直肠癌根治术的患者的预后，对于改善其临床预后至关重要。最近,据报道，T细胞免疫球蛋白和粘蛋白结构域蛋白3（Tim-3）及其配体半乳糖凝集素9（galectin-9）在各种肿瘤引起的免疫功能障碍中起着至关重要的作用，如结直肠癌。然而,他们的表情，生物学功能,结直肠癌的预后价值尚不清楚。本研究旨在探讨Tim-3和galectin-9表达水平与结直肠癌根治术患者临床病理特征及预后的关系。
■选择2018年2月至2019年3月在成都市第五人民医院接受结直肠癌根治术的患者171例。进行免疫组织化学以评估患者的癌组织样品和癌旁组织样品中Tim-3和半乳糖凝集素-9的表达水平。相应地分析Tim-3和半乳糖凝集素-9表达水平与患者的基线临床参数之间的关系。进行Kaplan-Meier分析以评估Tim-3和galectin-9表达水平与结直肠癌患者的无复发生存期(RFS)和总生存期(OS)之间的关联。进行Cox回归分析以确定与患者不良预后相关的因素。
■免疫组织化学结果显示，在70.18％（120/171）和32.16％（55/171）中观察到Tim-3和galectin-9的高表达水平，分别,结肠直肠癌组织，而低表达水平分别为29.82%(51/171)和67.84%(116/171),分别。此外，结直肠癌组织中Tim-3的表达得分明显高于癌旁组织,galectin-9在癌旁组织中的表达评分低于癌旁组织(P<0.05)。进一步分析发现Tim-3和galectin-9的表达与肿瘤浸润深度有关,血管浸润,临床分期(P<0.05)。在14-63个月的随访期间，171例患者中有7例失访。在剩下的患者中，49例和112例分别出现Tim-3和galectin-9异常低表达,而115例和52例分别高表达Tim-3和galectin-9。Kaplan-Meier生存分析显示，结直肠癌组织中Tim-3高表达患者的RFS和OS明显低于低表达患者（RFS：log-rank=22.66，P<0.001；OS：log-rank=19.71，P<0.001）。相反，半乳糖凝集素-9低表达患者的RFS和OS显著低于高表达患者(RFS:log-rank=19.45,P<0.001;OS:log-rank=22.24,P<0.001).多因素Cox分析表明TNM分期为Ⅲ期(HR=2.26,95%CI:1.20-5.68),Tim-3的高表达（HR=0.80，95%CI：0.33-0.91），半乳糖凝集素-9低表达(HR=1.80,95%CI:1.33~4.70)是影响患者RFS和OS的独立危险因素(P<0.05)。
■在结直肠癌组织中观察到Tim-3和半乳糖凝集素-9的异常表达。Tim-3的高表达和半乳糖凝集素-9的低表达与不良临床病理特征和预后密切相关。它们被确定为可能引发患者不良预后事件的独立影响因素。这些发现表明Tim-3和半乳糖凝集素-9具有作为新的治疗靶标和临床指标的潜力。
■选择2018年2月至2019年3月在成都市第五人民医院接受结直肠癌根治术的患者171例。进行免疫组织化学以评估患者的癌组织样品和癌旁组织样品中Tim-3和半乳糖凝集素-9的表达水平。相应地分析Tim-3和半乳糖凝集素-9表达水平与患者的基线临床参数之间的关系。进行Kaplan-Meier分析以评估Tim-3和galectin-9表达水平与结直肠癌患者的无复发生存期(RFS)和总生存期(OS)之间的关联。进行Cox回归分析以确定与患者不良预后相关的因素。
■免疫组织化学结果显示，在70.18％（120/171）和32.16％（55/171）中观察到Tim-3和galectin-9的高表达水平，分别,结肠直肠癌组织，而低表达水平分别为29.82%(51/171)和67.84%(116/171),分别。此外，结直肠癌组织中Tim-3的表达得分明显高于癌旁组织,galectin-9在癌旁组织中的表达评分低于癌旁组织(P<0.05)。进一步分析发现Tim-3和galectin-9的表达与肿瘤浸润深度有关,血管浸润,临床分期(P<0.05)。在14-63个月的随访期间，171例患者中有7例失访。在剩下的患者中，49例和112例分别出现Tim-3和galectin-9异常低表达,而115例和52例分别高表达Tim-3和galectin-9。Kaplan-Meier生存分析显示，结直肠癌组织中Tim-3高表达患者的RFS和OS明显低于低表达患者（RFS：log-rank=22.66，P<0.001；OS：log-rank=19.71，P<0.001）。相反，半乳糖凝集素-9低表达患者的RFS和OS显著低于高表达患者(RFS:log-rank=19.45,P<0.001;OS:log-rank=22.24,P<0.001).多因素Cox分析表明TNM分期为Ⅲ期(HR=2.26,95%CI:1.20-5.68),Tim-3的高表达（HR=0.80，95%CI：0.33-0.91），半乳糖凝集素-9低表达(HR=1.80,95%CI:1.33~4.70)是影响患者RFS和OS的独立危险因素(P<0.05)。
■在结直肠癌组织中观察到Tim-3和半乳糖凝集素-9的异常表达。Tim-3的高表达和半乳糖凝集素-9的低表达与不良临床病理特征和预后密切相关。它们被确定为可能引发患者不良预后事件的独立影响因素。这些发现表明Tim-3和半乳糖凝集素-9具有作为新的治疗靶标和临床指标的潜力。
