Unknown,Transcriptomics,Genomics,Proteomics

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Role of Anlotinib-induced CCL2 decrease in anti-angiogensis and response prediction for Non-Small Cell Lung Cancer therapy

ABSTRACT: Purpose: Our previous clinical trials have been demonstrated that Anlotinib can inhibit tumor growth upon refractory advanced non-small cell lung cancer (NSCLC) patients with the possibility mechanism of anti-angiogenesis. The present study sought to reveal the underlying molecular mechanism of Anlotinib-induced anti-angiogenesis in advanced NSCLC. Experimental Design: Computed tomography (CT) was used to evaluate the treatment effect of Anlotinib upon refractory advanced NSCLC patients. Transcriptome profiling was performed to identify the key gene expression alteration in NCI-H1975 cells before and after Anlotinib treatment. NCI-H1975 derived xenograft model was applied to investigate treatment effect and verify anti-angiogenesis mechanism of Anlotinib. Results: Anlotinib induces tumor cytotoxicity on refractory advanced NSCLC patients, NCI-H1975 derived xenograft models and lung adenocarcinoma cell lines. Transcriptome profiling revealed CCL2 blockade could be responsible for Anlotinib-induced anti-angiogenesis. NCI-H1975 derived xenograft model demonstrated Anlotinib-induced CCL2 blockade play an important role in anti-angiogenesis. Conclusions: This study not only offered the first evidence that Anlotinib inhibits angiogenesis via blocking CCL2 expression, but also provided a novel theoretical basis for the application of Anlotinib in advanced NSCLC patients.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Jun Lu

PROVIDER: E-MTAB-5997 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:In order to ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the anti-tumour effects of Trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via MTT assay. TSA and vorinostat both displayed strong anti-tumor activities in a proportion of NSCLC cell lines, and suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified NCI program. In addition, pathway analysis was performed with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine (SVM) algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the SVM model was validated by an additional seven cell lines, resulting in a prediction value of 100% in respect to determining response to TSA. Our results suggested that [1] HDAC inhibitors may be promising anticancer drugs to NSCLC, and [2] the nine gene classifer is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients. training sample set:; GSM94303 PC9; GSM94304 PC7; GSM94305 PC14; GSM94306 A549; GSM94308 LK2; GSM94313 RERF LC-KJ; GSM94314 RERF LC-MS; GSM94315 RERF-LC-AI; GSM94316 PC-1; GSM94317 PC-3; GSM94319 PC-10; GSM94323 ABC-1; GSM94324 EBC-1; GSM94325 LC2/ad; GSM94328 SQ-5; GSM94329 QG-56; test sample set:; GSM94307 LU65; GSM94326 LC1/sq; GSM94327 LC-1F; GSM254967 LCOK; GSM254968 LCD; GSM254969 H1650; GSM254970 H1975 Experiment Overall Design: gene expression analyis in lung cancer cell lines

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Role of Anlotinib-induced CCL2 decrease in anti-angiogensis and response prediction for Non-Small Cell Lung Cancer therapy

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