RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Contrasting Prognostic Roles of Stromal Periostin Expression and Immune Cells Infiltration in Colorectal Carcinoma.
Contrasting Prognostic Roles of Stromal Periostin Expression and Immune Cells Infiltration in Colorectal Carcinoma.
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间质 POSTN 表达和免疫细胞浸润,特别是联合(CD8+CD4),在 CRC 中提供了重要的预后信息,并可能指导治疗决策。
结直肠癌(CRC)是全球范围内癌症相关死亡最常见的原因之一。即使在相同的癌症分期中,CRC患者的预后也存在差异。肿瘤微环境(TME)在CRC中起着至关重要的作用,但其预后价值仍未完全明确。我们假设TME的不同组分可以通过多种方式影响患者结局。在本研究中,我们通过形态学和免疫组织化学(IHC)评估,探讨了CRC的TME中促纤维增生反应(DR)和免疫细胞浸润的预后意义。
对65例CRC患者进行了回顾性队列研究。在苏木精-伊红(H&E)染色切片中评估了DR的模式和TIL(肿瘤浸润淋巴细胞)(TILs)的密度。对periostin(POSTN)、CD8、CD4和CD68进行了IHC检测。研究了其与临床病理参数和总生存期(OS)的关联,包括在整个研究组和接受辅助治疗的亚组中。还评估了TME不同成分之间的关系。
高间质POSTN表达与不良预后和OS降低显著相关(p=0.005)。H&E染色切片中高密度的TILs、CD8⁺、CD4⁺以及联合(CD8+CD4)T淋巴细胞与OS改善相关(分别为p=0.03、0.02、p=0.03和<0.001),而高密度的CD68+巨噬细胞与不良预后相关(p=0.006)。联合(CD8+CD4)T淋巴细胞评分成为OS的独立预后因素(HR=0.1,p<0.001),优于其他所研究的参数。
A retrospective cohort of 65 CRC patients was examined. The patterns of DR and the density of tumor infiltrating lymphocytes (TILs) were evaluated in Hematoxylin and Eosin (H&E)-stained sections. IHC was performed for periostin (POSTN), CD8, CD4, and CD68. Associations with clinicopathological parameters and overall survival (OS), both in the entire study group and in the subgroup treated with adjuvant-therapy were investigated. The relation between different components of TME was also assessed.
High stromal POSTN expression correlated significantly with poor prognosis and reduced OS (p=0.005). High density of TILs in H&E-stained slides, CD8⁺, CD4⁺, and combined (CD8+CD4) T-lymphocytes was associated with improved OS (p=0.03, 0.02, p=0.03, and <0.001, respectively), while a high density of CD68+ macrophages was linked to poor prognosis (p=0.006). The combined (CD8+CD4) T-lymphocytes score emerged as an independent prognostic factor for OS (HR=0.1, p<0.001), outperforming the other studied parameters.
Stromal POSTN expression and immune cell infiltration, particularly combined (CD8+CD4), offer significant prognostic insights in CRC and may guide therapeutic decisions.
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