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:Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis.
Multicenter validation of CEACAM6 and FOXP3 as robust prognostic biomarkers in colon cancer: Combined immunohistochemical and transcriptomic analysis.
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结肠癌仍然是全球癌症相关死亡的主要原因之一,其中转移性疾病预后尤其差。为识别稳健的预后生物标志物,本多中心研究采用免疫组织化学和逆转录定量PCR评估了中国三家三级医院301例结肠癌标本中CEACAM6和FOXP3的表达,分析其与TIL(肿瘤浸润淋巴细胞)、临床病理特征及患者结局的关联。关键发现显示,与晚期(III-IV期)肿瘤相比,早期(I-II期)肿瘤表现出显著更高的CD3+、CD8+和CD45RO+ T细胞浸润(P<0.001),而FOXP3和CEACAM6表达在晚期和低分化肿瘤中显著升高(P<0.001)。
值得注意的是,CEACAM6过表达与CD3+、CD8+和CD45RO+ T细胞浸润呈负相关,但与FOXP3+ Tregs呈正相关。转录组分析进一步证实晚期肿瘤中CEACAM6和FOXP3 mRNA上调(P<0.001)。Kaplan-Meier生存分析表明,高CEACAM6和FOXP3表达与显著缩短的总生存期相关(P<0.001)。多因素Cox回归确定TNM分期、肿瘤分化、CEACAM6和FOXP3为独立预后因素。
本研究提供了CEACAM6和FOXP3作为结肠癌关键生物标志物的稳健多中心验证,强调其在免疫逃逸和肿瘤进展中的作用。这些发现支持将其潜在整合到临床风险分层和靶向免疫治疗的开发中。需要进一步的机制性和前瞻性研究以探索其治疗应用。
Colon cancer remains a leading cause of cancer-related mortality worldwide, with metastatic disease exhibiting particularly poor prognosis. To identify robust prognostic biomarkers, the present multicenter study employed immunohistochemistry and reverse transcription-quantitative PCR to evaluate CEACAM6 and FOXP3 expression in 301 colon cancer specimens from three tertiary hospitals in China, analyzing their associations with tumor-infiltrating lymphocytes, clinicopathological features and patient outcomes.
Key findings revealed that early-stage (I-II) tumors exhibited significantly higher infiltration of CD3 + , CD8 + and CD45RO + T cells compared with advanced-stage (III-IV) tumors (P<0. 001), while FOXP3 and CEACAM6 expression were significantly elevated in late-stage and poorly differentiated tumors (P<0. 001).
Notably, CEACAM6 overexpression correlated inversely with CD3 + , CD8 + and CD45RO + T-cell infiltration but positively with FOXP3 + Tregs. Transcriptomic analysis further confirmed upregulation of CEACAM6 and FOXP3 mRNA in advanced-stage tumors (P<0. 001). Kaplan-Meier survival analysis demonstrated that high CEACAM6 and FOXP3 expression were associated with significantly shorter overall survival (P<0.
001). Multivariate Cox regression identified TNM stage, tumor differentiation, CEACAM6 and FOXP3 as independent prognostic factors. The present study provides robust multicenter validation of CEACAM6 and FOXP3 as critical biomarkers in colon cancer, highlighting their roles in immune evasion and tumor progression.
These findings support their potential integration into clinical risk stratification and the development of targeted immunotherapies.
Further mechanistic and prospective studies are warranted to explore their therapeutic applications.
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