Deregulated mRNAs detected using microarray in 5 PR and 5 PD lung SCC patients.

<p>*Log2 (PR/PD).</p><p>Deregulated mRNAs detected using microarray in 5 PR and 5 PD lung SCC patients.</p

Long Noncoding RNAs Expression Patterns Associated with Chemo Response to Cisplatin Based Chemotherapy in Lung Squamous Cell Carcinoma Patients

<div><p>Background</p><p>There is large variability among lung squamous cell carcinoma patients in response to treatment with cisplatin based chemotherapy. LncRNA is potentially a new type of predictive marker that can identify subgroups of patients who benefit from chemotherapy and it will have great value for treatment guidance.</p><p>Methods</p><p>Differentially expressed lncRNAs and mRNA were identified using microarray profiling of tumors with partial response (PR) vs. with progressive disease (PD) from advanced lung squamous cell carcinoma patients treated with cisplatin based chemotherapy and validated by quantitative real-time PCR (qPCR). Furthermore, the expression of AC006050.3-003 was assessed in another 60 tumor samples.</p><p>Results</p><p>Compared with the PD samples, 953 lncRNAs were consistently upregulated and 749 lncRNAs were downregulated consistently among the differentially expressed lncRNAs in PR samples (Fold Change≥2.0-fold, <i>p</i> <0.05). Pathway analyses showed that some classical pathways, including “Nucleotide excision repair,” that participated in cisplatin chemo response were differentially expressed between PR and PD samples. Coding-non-coding gene co-expression network identified many lncRNAs, such as lncRNA AC006050.3-003, that potentially played a key role in chemo response. The expression of lncRNA AC006050.3-003 was significantly lower in PR samples compared to the PD samples in another 60 lung squamous cell carcinoma patients. Receiver operating characteristic curve analysis revealed that lncRNA AC006050.3-003 was a valuable biomarker for differentiating PR patients from PD patients with an area under the curve of 0.887 (95% confidence interval 0.779, 0.954).</p><p>Conclusions</p><p>LncRNAs seem to be involved in cisplatin-based chemo response and may serve as biomarkers for treatment response and candidates for therapy targets in lung squamous cell carcinoma.</p></div

Pathway analysis of the differentially expressed mRNAs.

<p>(A) Signaling pathways of upregulated mRNAs and downregulated mRNAs. The bar plot shows the top ten Enrichment score (−log10 (<i>P</i>-value)) value of the significant enrichment pathway. (B) The "Nucleotide excision repair" signal pathway shows modulation in repair of nonspecific DNA damage and is associated with cisplatin sensitivity. Yellow marked nodes are associated with downregulated genes, orange marked nodes are associated with upregulated or only whole dataset genes, and green nodes have no significance.</p

The expression of lncRNA AC006050.3-003 was validated by qPCR in samples of 60 patients with lung SCC stratified according to the chemo response (PR vs. PD) following cisplatin based chemotherapy.

<p>(A) lncRNA AC006050.3-003 was aberrantly expressed between PC and PD patients. The term 2^-ΔCt was used to describe the relative expression level of lncRNA (ΔCt  =  Ct_target−Ct_β-actin). ***<i>P</i><0.001 for patients with PD versus patients with PR (Student's t-test). (B) ROC analysis of the ability of lncRNA AC006050.3-003 levels to discriminate between PR and PD patients with lung SCC receiving cisplatin based chemotherapy.</p

LncRNA-mRNA-network was constructed based on the correlation analysis between the differential expressed lncRNAs and mRNAs.

<p>In the network, a regular hexagon node represents lncRNA, circular node represents the mRNA. A brown node represents an upregulated lncRNA or mRNA and a blue node represents a downregulated lncRNA or mRNA.</p

Validation of microarray data by qPCR.

<p>The differential expression of 5 lncRNAs (A) or 5 mRNAs (B) in samples of 10 patients by microarray was validated by qPCR. The relative expression level in PR samples was normalized by the PD samples. The heights of the columns in the chart represent the median fold changes (PR/PD) in expression across the patients for each of the validated lncRNAs or mRNAs. Fold changes were calculated by the 2^−ΔCt method. Fold changes  = mean2^−ΔCt (PR)/mean2^−ΔCt (PD), where ΔCt  =  Ct_target−Ct_β-actin.</p

Deregulated lncRNAs detected using microarray in 5 PR and 5 PD lung SCC patients.

<p>*Log2 (PR/PD).</p><p>Deregulated lncRNAs detected using microarray in 5 PR and 5 PD lung SCC patients.</p

Enhanced Antitumor Efficacy of Novel Biomimetic Platelet Membrane-Coated Tetrandrine Nanoparticles in Nonsmall Cell Lung Cancer

Nonsmall cell lung cancer (NSCLC) remains one of the leading causes of cancer-related death worldwide, posing a serious threat to global health. Tetrandrine (Tet) is a small molecule in traditional Chinese medicine with proven primary efficacy against multiple cancers. Although previous studies have demonstrated the potential anticancer effects of Tet on NSCLC, its poor water solubility has limited its further clinical application. Herein, a novel nanoparticle-based drug delivery system, platelet membrane (PLTM)-coated Tet-loaded polycaprolactone-b-poly(ethylene glycol)-b-polycaprolactone nanoparticles (PTeNPs), is proposed to increase the potency of Tet against NSCLC. First, tetrandrine nanoparticles (TeNPs) are created using an emulsion solvent evaporation method, and biomimetic nanoparticles (PTeNPs) are prepared by coating the nanoparticles with PLTMs. When coated with PLTMs, PTeNPs are considerably less phagocytized by macrophages than Tet and TeNPs. In addition, compared with Tet and TeNPs, PTeNPs can significantly inhibit the growth and invasion of NSCLC both in vitro and in vivo. With reliable biosafety, this drug delivery system provides a new method of sustained release and efficient anticancer effects against NSCLC, facilitating the incorporation of Tet in modern nanotechnology