RUNX1 预测预后不良，并与肾透明细胞癌的肿瘤进展相关。
RUNX1 predicts poor prognosis and correlates with tumor progression in clear cell renal carcinoma.
机构信息
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Shaanxi University of Chinese Medicine, Xi'an-Xianyang New Ecomic Zone, Shaanxi Province, China.
出版信息
Pathol Res Pract. 2023 Nov;251:154886. doi: 10.1016/j.prp.2023.154886. Epub 2023 Oct 12.
BACKGROUND
Runt-related transcription factor 1 (RUNX1), also called acute myeloid leukaemia 1, is a member of RUNX family of transcription factors. This family is composed of evolutionarily conserved transcription factors that function as critical lineage determinants in various tissues, however its function in cancer development and clinical significance in RCC are still unknown.
METHODS
We used paraffin-embedded tumor tissues from 100 patients and fresh-harvested and paired adjacent normal renal tissues from 15 RCC patients who underwent primary surgical resection in Xijing Hospital between 2018 and 2022. The expression level of RUNX1 was evaluated by immunohistochemistry and Western Blot. RUNX1 promoted tumor cells proliferation, migration and invasion were verified by CCK-8, wound-healing and transwell assays. Finally, we constructed a xenografts model of the 786-O cell lines to observe the effect of RUNX1 on tumorigenesis in vivo.
RESULTS
TCGA database showed higher RUNX1 expression levels in KIRC (kidney renal clear cell carcinoma). In overall survival analysis, RCC patients with higher RUNX1 expression level would have a shorter survival period than those with lower expression. Similarly, immunohistochemical results of our cohort also showed that RUNX1 was over-expression in cancer tissues than in corresponding non-cancer tissues. We also proved this result at protein level by western-blot. Meanwhile, prognostic and OS analyses of our cohort showed that the RUNX1 expression level was an individual prognostic factor in RCC patients. CCK-8, wound-healing and transwell assays proved that the overexpression of RUNX1 in Caki-1 cells promoted the proliferation, migration and invasion of the cells. Knocking down RUNX1 in 786-O cells inhibited the proliferation, migration and invasion of cells. The experimental results of xenografts model in nude mice showed that the knockdown of RUNX1 in 786-O cells slowed down the growth of tumor.
CONCLUSION
RUNX1 is a poor prognostic factor of clear cell renal carcinoma, which may provide a novel therapeutic target for ccRCC.
背景
runt 相关转录因子 1（RUNX1），也称为急性髓系白血病 1，是 runt 转录因子家族的成员。该家族由进化上保守的转录因子组成，在各种组织中作为关键的谱系决定因素发挥作用，但在癌症发展中的功能及其在 RCC 中的临床意义尚不清楚。
方法
我们使用了来自 100 名患者的石蜡包埋肿瘤组织和来自 2018 年至 2022 年期间在西京医院接受原发性手术切除的 15 名 RCC 患者的新鲜采集的配对相邻正常肾组织。通过免疫组织化学和 Western Blot 评估 RUNX1 的表达水平。通过 CCK-8、划痕愈合和 Transwell 测定验证 RUNX1 促进肿瘤细胞增殖、迁移和侵袭。最后，我们构建了 786-O 细胞系的异种移植模型，以观察 RUNX1 在体内对肿瘤发生的影响。
结果
TCGA 数据库显示 KIRC（肾透明细胞癌）中 RUNX1 的表达水平较高。在总生存分析中，RUNX1 表达水平较高的 RCC 患者的生存期比表达水平较低的患者短。同样，我们队列的免疫组织化学结果也表明，癌症组织中 RUNX1 的表达高于相应的非癌组织。我们还通过 Western blot 在蛋白质水平上证实了这一结果。同时，我们队列的预后和 OS 分析表明，RUNX1 的表达水平是 RCC 患者的个体预后因素。CCK-8、划痕愈合和 Transwell 测定证明 Caki-1 细胞中 RUNX1 的过表达促进了细胞的增殖、迁移和侵袭。786-O 细胞中 RUNX1 的敲低抑制了细胞的增殖、迁移和侵袭。裸鼠异种移植模型的实验结果表明，786-O 细胞中 RUNX1 的敲低减缓了肿瘤的生长。
结论
RUNX1 是透明细胞肾细胞癌的预后不良因素，可能为 ccRCC 提供新的治疗靶点。
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