Dataset Information

Differential proteomics analysis on plasma from anlotinib-treated advanced non-small cell lung cancer patients

ABSTRACT: Anlotinib has been demonstrated to be effective in advanced non-small cell lung cancer (NSCLC) patients. DNA-seq- and RNA-seq-based anlotinib molecular mechanism and biomarker screening have been introduced in previous studies. The underlying value of proteomics for anlotinib study is still unclear. In this study, 70 plasma samples were selected from 28 anlotinib-treated NSCLC patients (including 14 responders and 14 non-responders). LC-MS/MS analysis was performed on those samples with different time points including baseline, best response and progression disease. Bioinformatics analysis was performed to understand the underlying value of those differential proteins. Proteomics analysis suggested the differential proteins from responders after anlotinib administration potential play a role in the molecular mechanism characterization and biomarker screening. The differential proteins between responders and non-responders at baseline mainly contribute to biomarker screening. Integrative analysis indicated 43 proteins could be used as underlying biomarkers for clinical practice. Lastly, we selected ARHGDIB and demonstrated that it has some predictive value for anlotinib. Collectively, this study not only offered the first insight that the proteomic technology potentially be used for anlotinib molecular mechanism characterization, but also provided a basis for anlotinb biomarker screening via proteomics in the future.

ORGANISM(S): Homo Sapiens

SUBMITTER: Baohui Han

PROVIDER: PXD017919 | iProX | Thu Mar 05 00:00:00 GMT 2020

REPOSITORIES: iProX

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Publications

Screening anlotinib responders via blood-based proteomics in non-small cell lung cancer.

Lu Jun J Zhang Wei W Yu Keke K Zhang Lele L Lou Yuqing Y Gu Ping P Nie Wei W Qian Jie J Xu Jun J Wang Huimin H Zhong Hua H Han Baohui B

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20220801 8

Anlotinib has been demonstrated to be effective in advanced non-small cell lung cancer (NSCLC) patients. The response stratification of anlotinib remains unclear. In this study, plasma samples from 28 anlotinib-treated NSCLC patients (discovery cohort: 14 responders and 14 non-responders) were subjected to proteomic analysis, and plasma samples from 35 anlotinib-treated NSCLC patients (validation cohort) were subjected to validation analysis. Liquid chromatography-tandem mass spectrometry analys ...[more]

PMID: 35867072

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Project description:Purpose: To determine the 8-week disease control rate (DCR) of sorafenib monotherapy in patients with advanced non-small-cell lung cancer (NSCLC) in the BATTLE trial. Methods: Patients with pre-treated NSCLC consented to baseline biopsies for pre-specified biomarkers assessment and biomarker discovery. Sorafenib was given at 400 mg orally twice daily until tumor progression or unacceptable toxicity. Outcomes by pre-specified biomarkers were analyzed and a Sorafenib sensitivity signature developed using high-throughput gene expression profiles of NSCLC cell lines and baseline biopsies. Results: 105 patients were eligible and 98 patients were evaluable. Median age was 62 (range 34-81) years, 51% of patients were male, 75% were former/current smokers, and 89% had an ECOG performance status of 0-1. Median prior chemotherapies for stage IV NSCLC were two. Median follow-up was 9.4 (range: 1.3-32.2) months. Overall, 8-week DCR was 58.2%. Patients with EGFR mutations had significantly lower 8-week DCR compared to patients with wild-type tumors (23.1% vs. 64.2%, P=0.0119), and patients with K-RAS mutations had the highest 8-week DCR (67%). Most commonly reported treatment-related adverse events include hand-foot syndrome (59.6%), fatigue (42.3%), rash (40.4%), diarrhea (38.5%), and weight loss (38.5%). Sorafenib sensitivity signature developed in cell lines was associated with an improved outcome. Conclusion: Patients with wild-type EGFR, including those with K-RAS mutation, may benefit from sorafenib as opposed to patients with EGFR mutation. We identify a gene expression signature associated with an improved outcome in patients with wild-type EGFR treated with sorafenib. BATTLE-2 trial is ongoing to validate those results. ClinicalTrials.gov number, NCT00411671. Gene expression profiles were measured in 37 core biopsies from patients with refractory non-small cell lung cancer treated with sorafenib in the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial. We report a Sorafenib sensitivity gene expression signature trained in vitro (separate GEO submission), and tested in baseline biopsies collected in the BATTLE trial.

Dataset Information

Differential proteomics analysis on plasma from anlotinib-treated advanced non-small cell lung cancer patients

Publications

Screening anlotinib responders via blood-based proteomics in non-small cell lung cancer.

Similar Datasets

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