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大规模数字基因表达分析揭示了晚期肺癌腺癌和鳞状细胞癌中免疫检查点抑制剂治疗的不同预测特征。

Massive digital gene expression analysis reveals different predictive profiles for immune checkpoint inhibitor therapy between adenocarcinoma and squamous cell carcinoma of advanced lung cancer.

机构信息

Department of Thoracic Oncology, Kansai Medical University Hospital, 2-3-1, Shinmachi, Hirakata City, Osaka, 573-1191, Japan.

Discovery Technology Research, Ono Pharmaceutical, Co., Ltd., Osaka, Japan.

出版信息

BMC Cancer. 2022 Feb 8;22(1):154. doi: 10.1186/s12885-022-09264-2.

DOI:10.1186/s12885-022-09264-2
PMID:35135489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8822674/
Abstract

BACKGROUND

Immune checkpoint inhibitors prolong the survival of non-small cell lung cancer (NSCLC) patients. Although it has been acknowledged that there is some correlation between the efficacy of anti-programmed cell death-1 (PD-1) antibody therapy and immunohistochemical analysis, this technique is not yet considered foolproof for predicting a favorable outcome of PD-1 antibody therapy. We aimed to predict the efficacy of nivolumab based on a comprehensive analysis of RNA expression at the gene level in advanced NSCLC.

METHODS

This was a retrospective study on patients with NSCLC who were administered nivolumab at the Kansai Medical University Hospital. To identify genes associated with response to anti-PD-1 antibodies, we grouped patients into responders (complete and partial response) and non-responders (stable and progressive disease) to nivolumab therapy. Significant genes were then identified for these groups using Welch's t-test.

RESULTS

Among 42 analyzed cases (20 adenocarcinomas and 22 squamous cell carcinomas), enhanced expression of MAGE-A4, BBC3, and OTOA genes was observed in responders with adenocarcinoma, and enhanced expression of DAB2, HLA-DPB,1 and CDH2 genes was observed in responders with squamous cell carcinoma.

CONCLUSIONS

This study predicted the efficacy of nivolumab based on a comprehensive analysis of mRNA expression at the gene level in advanced NSCLC. We also revealed different gene expression patterns as predictors of the effectiveness of anti PD-1 antibody therapy in adenocarcinoma and squamous cell carcinoma.

摘要

背景

免疫检查点抑制剂延长了非小细胞肺癌(NSCLC)患者的生存期。虽然已经认识到抗程序性细胞死亡-1(PD-1)抗体治疗的疗效与免疫组织化学分析之间存在一定的相关性,但该技术尚不能完全预测 PD-1 抗体治疗的良好预后。我们旨在通过对晚期 NSCLC 的基因水平 RNA 表达进行综合分析来预测纳武单抗的疗效。

方法

这是一项在关西医科大学医院接受纳武单抗治疗的 NSCLC 患者的回顾性研究。为了确定与抗 PD-1 抗体反应相关的基因,我们将患者分为纳武单抗治疗的应答者(完全和部分缓解)和无应答者(稳定和进展性疾病)。然后使用 Welch's t 检验对这些组进行了显着基因的鉴定。

结果

在分析的 42 例病例中(20 例腺癌和 22 例鳞状细胞癌),观察到腺癌应答者中 MAGE-A4、BBC3 和 OTOA 基因的表达增强,而鳞状细胞癌应答者中 DAB2、HLA-DPB1 和 CDH2 基因的表达增强。

结论

本研究基于晚期 NSCLC 的基因水平 mRNA 表达的综合分析预测了纳武单抗的疗效。我们还揭示了不同的基因表达模式,作为预测抗 PD-1 抗体治疗在腺癌和鳞状细胞癌中的有效性的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a477/8822674/a1ca7081d44f/12885_2022_9264_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a477/8822674/a1ca7081d44f/12885_2022_9264_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a477/8822674/a1ca7081d44f/12885_2022_9264_Fig1_HTML.jpg

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Precision Pathology as Part of Precision Medicine: Are We Optimizing Patients' Interests in Prioritizing Use of Limited Tissue Samples?精准病理学作为精准医学的一部分:我们是否在优先使用有限组织样本时优化了患者的利益?
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