半乳糖凝集素-9 在非小细胞肺癌中的作用。
Galectin-9 in non-small cell lung cancer.
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China.
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China; Tongji University, No. 1239 Siping Road, Shanghai, 200433, People's Republic of China.
出版信息
Lung Cancer. 2019 Oct;136:80-85. doi: 10.1016/j.lungcan.2019.08.014. Epub 2019 Aug 16.
OBJECTIVES
Lung cancer has the highest incidence and fatality among all cancers. Our research analyzed the expression of galectin-9 on non-small cell lung cancer (NSCLC) tumor cells and tumor infiltrating lymphocytes (TILs).
MATERIALS AND METHODS
We analyzed the expression level of galectin-9 protein in 136 NSCLC primary tumor samples by immunohistochemistry (IHC).
RESULTS
We tested 136 surgical resected primary NSCLC tumor tissues for galectin-9 from Medical University of Gdansk, Poland. We found that on tumor cells, galectin-9 level only had correlation with T cell immunoglobulin and mucin-domain containing-3 (TIM-3) level (Correlation Coefficient = 0.360, p < 0.001). On TILs, galectin-9 level had broad connections with other checkpoints including programmed cell death protein-1 (PD-1) (Correlation Coefficient = 0.332, p < 0.001), programmed cell death-ligand 1 (PD-L1) (Correlation Coefficient = 0.247, p = 0.004) and TIM-3 (Correlation Coefficient = 0.350, p < 0.001). Interestingly, galectin-9 level on TILs also had positive relation with PD-L1 level on tumor cells (Correlation Coefficient = 0.278, p = 0.001), galectin-9 level on tumor cells (Correlation Coefficient = 0.181, p = 0.035) and TIL percentage (Correlation Coefficient = 0.236, p = 0.006). High level of galectin-9 on TILs indicated shorter RFS (recurrence-free survival) (RFS 1.82 years, 95% CI 0.795-2.845 vs. 0.67 years, 95% CI 0.086-1.254, P = 0.033). Patients with galectin-9 positive tumor cells display longer overall survival (OS) (1.76 years, 95% CI 0.222-3.298 vs. 3.10 years, 95% CI 2.662-3.538, P = 0.039) CONCLUSIONS: We found galectin-9 expression on both NSCLC tumor cells and TILs. Galectin-9 expression was found in all NSCLC pathological type. Galectin-9 level on TILs had correlation with TIM-3, PD-1 and PD-L1 level. On tumor cells, galectin-9 level had correlation with TIM-3 level. Patients with low galectin-9 level on tumor cells or high galectin-9 level on TILs were more likely to have poor prognosis.
目的
肺癌是所有癌症中发病率和死亡率最高的癌症。我们的研究分析了半乳糖凝集素-9 在非小细胞肺癌 (NSCLC) 肿瘤细胞和肿瘤浸润淋巴细胞 (TIL) 中的表达。
材料和方法
我们通过免疫组织化学 (IHC) 分析了来自波兰格但斯克医科大学的 136 例 NSCLC 原发性肿瘤样本中半乳糖凝集素-9 蛋白的表达水平。
结果
我们对半乳糖凝集素-9 在波兰格但斯克医科大学的 136 例手术切除的原发性 NSCLC 肿瘤组织中的表达进行了测试。我们发现，在肿瘤细胞上，半乳糖凝集素-9 水平仅与 T 细胞免疫球蛋白和粘蛋白结构域包含-3 (TIM-3) 水平相关 (相关系数=0.360，p<0.001)。在 TILs 上，半乳糖凝集素-9 水平与其他检查点广泛相关，包括程序性细胞死亡蛋白-1 (PD-1) (相关系数=0.332，p<0.001)、程序性细胞死亡配体 1 (PD-L1) (相关系数=0.247，p=0.004) 和 TIM-3 (相关系数=0.350，p<0.001)。有趣的是，TIL 上的半乳糖凝集素-9 水平也与肿瘤细胞上的 PD-L1 水平呈正相关 (相关系数=0.278，p=0.001)、肿瘤细胞上的半乳糖凝集素-9 水平 (相关系数=0.181，p=0.035) 和 TIL 百分比 (相关系数=0.236，p=0.006)。TIL 上高半乳糖凝集素-9 水平预示着较短的无复发生存期 (RFS) (RFS 1.82 年，95%CI 0.795-2.845 与 0.67 年，95%CI 0.086-1.254，p=0.033)。半乳糖凝集素-9 阳性肿瘤细胞的患者具有更长的总生存期 (OS) (1.76 年，95%CI 0.222-3.298 与 3.10 年，95%CI 2.662-3.538，p=0.039)。
结论
我们发现半乳糖凝集素-9 在 NSCLC 肿瘤细胞和 TILs 上均有表达。半乳糖凝集素-9 在所有 NSCLC 病理类型中均有表达。TIL 上的半乳糖凝集素-9 水平与 TIM-3、PD-1 和 PD-L1 水平相关。在肿瘤细胞上，半乳糖凝集素-9 水平与 TIM-3 水平相关。肿瘤细胞上半乳糖凝集素-9 水平低或 TIL 上半乳糖凝集素-9 水平高的患者预后更差。
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