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

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Cancer Drug Resistance 2021年第4期4卷 1061-1071页

作者： Luis E.Raez Kathleen Danenberg Daniel Sumarriva Joshua Usher jacob sands Aurelio Castrellon Pablo Ferraro Adriana Milillo Eric Huang Patrick Soon-Shiong Sandeep Reddy Peter Danenberg Thoracic Oncology Program Memorial Cancer Institute/Memorial Healthcare SystemFlorida International UniversityMiamiFL 33199USA Nant Health Culver City2040 E Mariposa AveEl SegundoCA 90245USA Thoracic Oncology Program Dana Farber Cancer InstituteHarvard Medical SchoolBostonMA 02215USA Burning Rock Beijing 100022China Department of Biochemistry and Molecular Medicine University of Southern CaliforniaLos AngelesCA 90089USA

Aim: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 ***:Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy,52 with NSCLC,50 with breast cancer,and 25 with *** 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 *** the concordance study of liquid biopsies and tissue biopsies,the isolated RNA was analyzed by RNAseq for the expressions of 13 *** had to close the study early due to a lack of follow-up during the Covid-19 ***:We collected a total of 373 blood *** cfRNA PCR signals after RT were about 50-fold higher than those of *** 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 *** 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)*** expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with ***-treatment levels of PD-L1 were predictive of response in patients treated with ***:Changes in cfRNA correlate with clinical response to the *** cfRNA may be useful in predicting clinical ***-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.

关键词： cfRNA cfDNA liquid biopsies NSCLC PD-L1

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