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将循环游离RNA（cfRNA）作为评估转移性肺癌和其他肿瘤患者临床治疗效果的工具。

Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors.

作者信息

Raez Luis E, Danenberg Kathleen, Sumarriva Daniel, Usher Joshua, Sands Jacob, Castrellon Aurelio, Ferraro Pablo, Milillo Adriana, Huang Eric, Soon-Shiong Patrick, Reddy Sandeep, Danenberg Peter

机构信息

Thoracic Oncology Program, Memorial Cancer Institute/Memorial Healthcare System, Florida International University, Miami, FL 33199, USA.

Nant Health, Culver City, 2040 E Mariposa Ave, El Segundo, CA 90245, USA.

出版信息

Cancer Drug Resist. 2021 Dec 13;4(4):1061-1071. doi: 10.20517/cdr.2021.78. eCollection 2021.

DOI:10.20517/cdr.2021.78
PMID:35582387
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8992448/
Abstract

We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. gene expression may provide a biomarker to predict response to PD-L1 inhibition.

摘要

我们报告了一项探索性分析，将循环游离RNA（cfRNA）作为一种生物标志物，用于监测非小细胞肺癌（NSCLC）、乳腺癌和结直肠癌（CRC）的临床反应。在NSCLC队列中，还进行了一项将cfRNA作为测量PD-L1表达的方法并与临床反应进行比较的分析。从127例正在接受治疗的转移性疾病患者中采集血样，其中52例为NSCLC患者，50例为乳腺癌患者，25例为CRC患者。从分级血浆中纯化cfRNA，逆转录（RT）后，以β-肌动蛋白表达作为cfDNA和cfRNA相对量的替代指标，通过实时聚合酶链反应（qPCR）分析总cfRNA和PD-L1的基因表达。对于液体活检和组织活检的一致性研究，通过RNA测序分析分离出的RNA中13个基因的表达。由于在新冠疫情期间缺乏随访，我们不得不提前结束研究。我们共采集了373份血样。RT后平均cfRNA PCR信号比cfDNA高约50倍。所有患者均检测到cfRNA，而88%的患者检测到cfDNA。血液和实体瘤组织中13个基因的表达水平具有高度一致性。治疗过程中cfRNA水平的变化与治疗反应相关，疾病进展（PD）时升高，部分缓解（PR）时下降。接受免疫治疗的患者中，随着时间推移，PD-L1的表达在PR时降低，在PD时升高。免疫治疗患者治疗前的PD-L1水平可预测反应。cfRNA的变化与治疗的临床反应相关。总cfRNA可能有助于预测临床结果。基因表达可能提供一种生物标志物来预测对PD-L1抑制的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/60d84f80065e/cdr-4-1061.fig.8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/1eed9667043c/cdr-4-1061.fig.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/78111c2a26d0/cdr-4-1061.fig.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/01d3ef7958b8/cdr-4-1061.fig.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/d1996fcde58b/cdr-4-1061.fig.4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/4a805798ef5b/cdr-4-1061.fig.5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/fdf367701efb/cdr-4-1061.fig.6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/f59f36b05365/cdr-4-1061.fig.7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/60d84f80065e/cdr-4-1061.fig.8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/1eed9667043c/cdr-4-1061.fig.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/78111c2a26d0/cdr-4-1061.fig.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/01d3ef7958b8/cdr-4-1061.fig.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/d1996fcde58b/cdr-4-1061.fig.4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/4a805798ef5b/cdr-4-1061.fig.5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/fdf367701efb/cdr-4-1061.fig.6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/f59f36b05365/cdr-4-1061.fig.7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a2/8992448/60d84f80065e/cdr-4-1061.fig.8.jpg

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