在HNSCC中CTTN过度表达抑制了Anoikis-apoptosis
Zheng-Zhong Shen1, Qiu-Shuang Xu2, Chuan-Ji Wu1
1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Third Section of Ren Min Nan Rd, Chengdu, 610041, Sichuan, China.
研究人员确定了与亡相关的基因特征,以预测头部和部状细胞癌 (HNSCC) 的预后. 抑制CTTN基因抑制了HNSCC的生长,这表明CTTN是HNSCC的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症基因组学 癌症基因组学
背景情况:
- 头部和部状细胞癌 (HNSCC) 是一种普遍存在的恶性瘤,在这种恶性瘤中,对阿诺基斯 (通过脱落诱导的亡) 的耐药性促进了入侵和转移.
- 确定可靠的生物标志物用于HNSCC预后和治疗向仍然是一个挑战.
- 阿诺基的抗性是癌症的标志,有助于瘤细胞的生存,入侵和迁移.
研究的目的:
- 开发和验证与亡相关的基因特征,用于预测HNSCC患者的预后.
- 调查已识别的关键基因CTTN在HNSCC细胞亡,入侵和潜在的治疗标中的作用.
主要方法:
- 在癌症基因组图集 (TCGA) -HNSC队列上利用LASSO-Cox回归分析,建立基于亡相关基因的预后模型.
- 开发了一种基于风险评分的诺姆图,用于HNSCC的生存预测.
- 在HNSCC细胞系和患者衍生器官 (PDO) 中验证了基因CTTN的功能,使用PI染色,免疫光 (IF) 和西部斑点 (WB) 等技术.
- 分析了CTTN表达及其在泛癌和HNSCC中的作用,包括其细胞局部化.
主要成果:
- 为了预测HNSCC患者的存活率,建立了一个包含15个基因 (CTTN,PLAU,PLK1,BID,MAPK11,SPINK1,VEGFA,PIK3R2,CEACAM1,MAD2L1,SLCO1B3,TFDP1,SFRP1,SPP1,SPHK1) 的新型亡相关基因签名.
- 鉴定出CTTN基因是关键的参与者;其敲除损害了细胞骨的形成,降低了抗亡能力,并在HNSCC-PDOs中显著抑制了瘤生长.
- 发现CTTN在大多数瘤中表达高,特别是在HNSCC.内的上皮细胞和纤维细胞中.
结论:
- 与亡相关的基因签名可以有效地预测HNSCC患者的预后.
- 基因CTTN在HNSCC的亡和侵袭中发挥着关键作用,显示出作为HNSCC治疗的治疗点的巨大潜力.
- 准CTTN可能提供一种新的策略,以抑制HNSCC的进展并改善患者的治疗结果.
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