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作者：SCI天天读
SCI
31 May 2023
Immune infiltration in tumor and adjacent non-neoplastic regions co-determines patient clinical outcomes in early-stage lung cancer
(J Thorac Oncol IF: 15.61)
Cheng C, Nguyen TT, Tang M, et al. Immune infiltration in tumor and adjacent non-neoplastic regions co-determines patient clinical outcomes in early-stage lung cancer [published online ahead of print, 2023 May 3]. J Thorac Oncol. 2023;S1556-0864(23)00526-9. doi:10.1016/j.jtho.2023.04.022
Abstract 摘要
In recent years, the fraction of non-small cell lung cancer (NSCLC) patients diagnosed at an early stage has been increasing continuously. In this study we analyzed samples and data collected from 119 samples from 67 early-stage NSCLC patients, including 52 pairs of tumor and adjacent non-neoplastic samples, and performed RNA-seq analysis with high sequencing depth. We found that immune related genes were highly enriched among the differentially expressed genes and observed significantly higher inferred immune infiltration levels in adjacent non-neoplastic samples compared to the tumor samples. In survival analyses, the infiltration of certain immune cell types in tumor, but not adjacent non-neoplastic, samples were associated with overall patient survival, and excitingly, the differential infiltration between paired samples (tumor minus non- neoplastic) was more prognostic than expression in either non-neoplastic or tumor tissues. We also performed B cell receptor (BCR) and T cell receptor (TCR) repertoire analysis and observed more BCR/TCR clonotypes and increased BCR clonality in tumor than non-neoplastic samples. Finally, we carefully quantified the fraction of the 5 histological subtypes in our adenocarcinoma samples and found that higher histological pattern complexity was associated with higher immune infiltration and low TCR clonality in the tumor-proximal regions. In summary, our results indicated significantly differential immune characteristics between tumor and adjacent non-neoplastic samples and suggested the two regions provided complementary prognostic values in early-stage NSCLCs.
近年来，早期诊断的非小细胞肺癌（NSCLC）患者的比例持续增加。在这项研究中，我们分析了来自67名早期NSCLC患者的119个样本和数据，包括52对肿瘤和邻近非肿瘤样本，并进行了高测序深度的RNA-seq分析。我们发现免疫相关的基因在差异表达的基因中高度富集，并观察到与肿瘤样本相比，邻近非肿瘤样本的推断免疫浸润水平明显更高。在生存分析中，某些免疫细胞类型在肿瘤中的浸润，而不是在邻近的非肿瘤样本中的浸润，与患者的总生存率有关，令人兴奋的是，配对样本（肿瘤减去非肿瘤）之间的差异浸润比在非肿瘤或肿瘤组织中的表达更具预后性。我们还进行了B细胞受体（BCR）和T细胞受体（TCR）剧目分析，观察到肿瘤中的BCR/TCR克隆型多于非肿瘤样本，且BCR克隆性增加。最后，我们仔细量化了腺癌样本中5种组织学亚型的比例，发现较高的组织学模式复杂性与较高的免疫浸润和肿瘤近端区域的低TCR克隆性有关。总之，我们的结果表明，肿瘤和邻近的非肿瘤样本之间的免疫特征有明显的差异，并提示这两个区域在早期NSCLCs中提供互补的预后价值。
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原文地址：http://mp.weixin.qq.com/s?src=11×tamp=1685606614&ver=4563&signature=rndki*QkebsRBKap9xZy1IF3fpO3OxENuG1tYXiYDRcpDCeNtdGH4D*9I7cA19g7fdDVyjdzT1NkTFesL0AjGCwE8SKcbEjvP3ZHoRimoSUq-bhmfhwdPekiOGQUxnWc&new=1 |
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