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:Genomic and transcriptomic significance of multiple primary lung cancers detected by next-generation sequencing in clinical settings.
Genomic and transcriptomic significance of multiple primary lung cancers detected by next-generation sequencing in clinical settings.
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有效诊断和理解多原发肺癌(MPLC)肺内转移(IM)的机制有助于临床管理。然而,临床上实际使用的检测 panel 各不相同。目前关于 MPLC 和 IM 肿瘤微环境(TME)的研究尚不充分。
因此,进一步研究两种疾病之间的鉴别诊断及 TME 差异至关重要。共纳入 214 例伴多发肿瘤的非小细胞肺癌患者,对 507 份样本进行 DNA 测序(NGS 10)。随后对 32 例患者的标本进行 DNA 和 RNA 测序(master panel),比较每例患者内肿瘤之间及患者之间的 TME 特征以及差异表达基因。根据 NGS 10 结果对 4 例患者重新分组。Master panel 明确了 6 例未确定患者的分类。MPLC 的 TME 表现出自然杀伤(NK)细胞、CD56dim NK 细胞、内皮细胞等高度浸润,P < 0.05。相反,IM 中 B 细胞、活化 B 细胞、调节性细胞、未成熟树突状细胞等大量浸润,P < 0.001。NECTIN4 和 LILRB4 mRNA 在 MPLC 中下调(P < 0.0001)。
此外,NECTIN4(P < 0.05)和 LILRB4 与 MPLC 中改善的无病生存期相关。总之,通过病理联合 NGS 10 检测从 MPLC 中筛选出 IM,随后对难以鉴别的患者使用大 NGS panel。MPLC 较好的预后可能与免疫激活型 TME 以及 NECTIN4 和 LILRB4 下调有关,后者被视为潜在的药物治疗靶点。
Effective diagnosis and understanding of the mechanism of intrapulmonary metastasis (IM) from multiple primary lung cancers (MPLC) aid clinical management.
However, the actual detection panels used in the clinic are variable. Current research on tumor microenvironment (TME) of MPLC and IM is insufficient.
Therefore, additional investigation into the differential diagnosis and discrepancies in TME between two conditions is crucial. Two hundred and fourteen non-small cell lung cancer patients with multiple tumors were enrolled and 507 samples were subjected to DNA sequencing (NGS 10). Then, DNA and RNA sequencing (master panel) were performed on the specimens from 32 patients, the TME profiles between tumors within each patient and across patients and the differentially expressed genes were compared.
Four patients were regrouped with NGS 10 results. Master panel resolved the classifications of six undetermined patients. The TME in MPLC exhibited a high degree of infiltration by natural killer (NK) cells, CD56dim NK cells, endothelial cells, etc. , P < 0. 05. Conversely, B cells, activated B cells, regulatory cells, immature dendritic cells, etc. , P < 0. 001, were heavily infiltrated in the IM. NECTIN4 and LILRB4 mRNA were downregulated in the MPLC (P < 0. 0001).
Additionally, NECTIN4 (P < 0. 05) and LILRB4 were linked to improved disease-free survival in the MPLC.
In conclusion, IM is screened from MPLC by pathology joint NGS 10 detections, followed by a large NGS panel for indistinguishable patients. A superior prognosis of MPLC may be associated with an immune-activating TME and the downregulation of NECTIN4 and LILRB4 considered as potential drug therapeutic targets.
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