Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
Pathol Res Pract. 2022 Sep;237:154039. doi: 10.1016/j.prp.2022.154039. Epub 2022 Jul 21.
Granulysin (GNLY) is a cytolytic and proinflammatory molecule which also acts as an immune alarmin. The multifunctional nature of this molecule has made it challenging to define its full potential as a biomarker in breast cancer.
To evaluate the prognostic value of intratumoral GNLY in primary breast cancer patients and its association with established clinicopathological parameters.
The study included 69 node-negative breast cancer patients with known clinicopathological parameters, all of whom had not received any prior hormonal or chemotherapeutic systemic therapy that would interfere with the course of disease. The median follow-up period was 144 months. Steroid hormone receptor status was determined by ligand-binding assay and HER2 status by chromogenic in situ hybridisation (CISH). Intratumoral GNLY mRNA levels were determined by RT-qPCR. Prognostic performance was evaluated by the receiver operating characteristic (ROC), Cox proportional hazards regression and Kaplan-Meier analysis. Classification of patients into GNLY and GNLY subgroups was performed by the use of the outcome-oriented cut-off point categorisation approach.
There was a significant difference between GNLY values of patients without any recurrences and those with local or distant recurrences (Mann-Whitney test, p = 0.05 and p = 0.02, respectively). None of the tested parameters showed prognostic significance for local and distant recurrences when combined. When distant metastases and local recurrences were separated as events, the best prognostic performance was observed for GNLY as compared with any clinicopathological parameter (AUC=0.24 and p = 0.04 for local events; AUC=0.71 and p = 0.03 for distant events). Local recurrence incidence was 0% for the GNLY subgroup and 19% for the GNLY subgroup; however distant recurrence incidence was 24% for the GNLY subgroup but only 3% for the GNLY subgroup (Kaplan-Meier analysis). A significant positive correlation was found between intratumoral ER and GNLY levels, and a significant negative correlation between tumour grade and GNLY levels.
High levels of granulysin prognosticate low risk of local recurrence but a high risk of distant metastasis in primary, untreated, breast cancer patients.
颗粒溶素 (GNLY) 是一种细胞溶解和促炎分子，也是一种免疫警报素。该分子的多功能性质使其作为乳腺癌生物标志物的全部潜力难以确定。
评估原发性乳腺癌患者肿瘤内 GNLY 的预后价值及其与既定临床病理参数的相关性。
该研究纳入了 69 例淋巴结阴性乳腺癌患者，这些患者均具有已知的临床病理参数，且均未接受任何先前可能干扰疾病进程的激素或化学治疗全身治疗。中位随访时间为 144 个月。甾体激素受体状态通过配体结合测定法确定，HER2 状态通过显色原位杂交法 (CISH) 确定。通过 RT-qPCR 测定肿瘤内 GNLY mRNA 水平。通过接受者操作特征 (ROC)、Cox 比例风险回归和 Kaplan-Meier 分析评估预后性能。通过使用面向结果的截止点分类方法将患者分为 GNLY 和 GNLY 亚组。
无任何复发患者的 GNLY 值与局部或远处复发患者的 GNLY 值之间存在显著差异（Mann-Whitney 检验，p=0.05 和 p=0.02）。当联合使用时，测试的参数均未显示出对局部和远处复发的预后意义。当将远处转移和局部复发分别作为事件时，与任何临床病理参数相比，GNLY 表现出最佳的预后性能（局部事件的 AUC=0.24 和 p=0.04；远处事件的 AUC=0.71 和 p=0.03）。GNLY 亚组的局部复发发生率为 0%，GNLY 亚组的局部复发发生率为 19%；然而，GNLY 亚组的远处复发发生率为 24%，GNLY 亚组的远处复发发生率为 3%（Kaplan-Meier 分析）。肿瘤内 ER 和 GNLY 水平之间存在显著正相关，肿瘤分级和 GNLY 水平之间存在显著负相关。
在原发性、未经治疗的乳腺癌患者中，高水平的颗粒溶素预示着局部复发风险低，但远处转移风险高。
