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:Combinatory statuses of tumor stromal percentage and tumor infiltrating lymphocytes as prognostic factors in stage III colorectal cancers.
Combinatory statuses of tumor stromal percentage and tumor infiltrating lymphocytes as prognostic factors in stage III colorectal cancers.
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这些发现提示,该联合状态可能作为 III 期 CRCs 的预后参数。
肿瘤间质和TIL(肿瘤浸润淋巴细胞)是肿瘤微环境的主要组成部分,但它们对结直肠癌(CRC)患者预后的影响不同。预计联合考察肿瘤间质百分比(TSP)和TIL状态可提供更有力的预后信息,但此前尚未在CRC中研究。
采用计算机辅助方法,评估487例接受辅助化疗的Ⅲ期CRC患者的TSP以及CD3-TIL或CD8-TIL密度。以表皮内TIL(iTIL)和间质TIL(sTIL)密度的中位数为截断值,将CRC分为iTIL或sTIL低、高组。再按TSP五分位数(Q1至Q5)分组,并将Q5定义为高TSP组、Q1至Q4定义为低TSP组。
多变量生存分析显示,CD8 iTIL密度与TSP的组合是癌症特异性生存和无复发生存的独立预后参数。CD8 iTIL低且TSP高的CRC患者生存最差。联合状态的预后判别能力强于单独使用CD8 iTIL密度或TSP。在独立的Ⅲ期CRC队列中,多变量生存分析验证了联合状态的预后价值。
联合状态可能成为Ⅲ期CRC的预后指标。仍需在大规模Ⅲ期CRC患者队列中进一步验证其预后能力。
Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3-TIL or CD8-TIL densities using computer-aided methodology. With cut-off values set at median values for intraepithelial TIL (iTIL) and stromal TIL (sTIL) densities, CRCs were sorted into low and high iTIL or sTIL groups. CRCs were classified into five quintile (Q1-Q5) groups according to their TSP and divided into high TSP (Q5) and low TSP (Q1-4) groups.
The combination of CD8 iTIL density and TSP was found to be an independent prognostic parameter in multivariate survival analysis in terms of cancer-specific survival and recurrence-free survival. CRCs with low CD8 iTIL density and high TSP showed the worst survival. The combinatory status showed more prognostic power than CD8 iTIL density or TSP alone. Multivariate survival analysis in an independent cohort of stage III CRC validated the prognostic power of the combinatory statuses.
The findings suggest that the combinatory status might serve as a prognostic parameter in stage III CRCs. Further research in a large-scale cohort of patients with stage III CRC is needed to validate the prognostic power of the combinatory status.
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