An inflammatory-related genes signature based model for prognosis prediction in breast cancer

Background:Breast cancer has become the most common malignant tumor in the world.It is vital to discover novel prognostic biomarkers despite the fact that the majority of breast cancer patients have a good prognosis because of the high heterogeneity of breast cancer,which causes the disparity in prognosis.Recently,inflammatory-related genes have been proven to play an important role in the development and progression of breast cancer,so we set out to investigate the predictive usefulness of inflammatory-related genes in breast malignancies.Methods:We assessed the connection between Inflammatory-Related Genes(IRGs)and breast cancer by studying the TCGA database.Following differential and univariate Cox regression analysis,prognosis-related differentially expressed inflammatory genes were estimated.The prognostic model was constructed through the Least Absolute Shrinkage and Selector Operation(LASSO)regression based on the IRGs.The accuracy of the prognostic model was then evaluated using the Kaplan-Meier and Receiver Operating Characteristic(ROC)curves.The nomogram model was established to predict the survival rate of breast cancer patients clinically.Based on the prognostic expression,we also looked at immune cell infiltration and the function of immune-related pathways.The CellMiner database was used to research drug sensitivity.Results:In this study,7 IRGs were selected to construct a prognostic risk model.Further research revealed a negative relationship between the risk score and the prognosis of breast cancer patients.The ROC curve proved the accuracy of the prognostic model,and the nomogram accurately predicted survival rate.The scores of tumorinfiltrating immune cells and immune-related pathways were utilized to calculate the differences between the low-and high-risk groups,and then explored the relationship between drug susceptibility and the genes that were included in the model.Conclusion:These findings contributed to a better understanding of the function of inflammatory-related genes in breast cancer,and the prognostic risk model provides a potentially promising prognostic strategy for breast cancer.

CHRM3 is a novel prognostic factor of poor prognosis andpromotes glioblastoma progression via activation of oncogenicinvasive growth factors

Glioblastoma(GBM)is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy.Clarification of molecular mechanisms of GBM’s characteristic invasive growth is urgently needed to improve the poor prognosis.Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor(CHRM3)were significantly higher in the recurrent samples than in the primary samples.Moreover,immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis,consistent with The Cancer Genome Atlas database.Knockdown of CHRM3 inhibited GBM cell growth and invasion.An assay of orthotopic GBM animal model in vivo indicated that inhibition of CHRM3 significantly suppressed GBM progression with prolonged survival time.Transcriptome analysis revealed that CHRM3 knockdown significantly reduced an array of classic factors involved in cancer invasive growth,including MMP1/MMP3/MMP10/MMP12 and CXCL1/CXCL5/CXCL8.Taken together,CHRM3 is a novel and vital factor of GBM progression via regulation of multiple oncogenic genes and may serve as a new biomarker for prognosis and therapy of GBM patients.

L1CAM overexpression promotes tumor progression through recruitment of regulatory T cells in esophageal carcinoma

Objective:L1 cell adhesion molecule(L1 CAM)exhibits oncogenic activity in tumors.However,the link between L1 CAM and the tumor microenvironment remains poorly understood in patients with esophageal squamous cell carcinoma(ESCC).In this study,we investigated how L1 CAM expression in ESCC affects the oncogenic characteristics of tumor cells and the tumor microenvironment.Methods:Human ESCC samples were collected,and the m RNA and protein levels of L1 CAM were examined by real-time PCR and immunohistochemistry.Overexpression and knockdown gene expression assays were used for mechanistic studies.The cell proliferation and cell cycle were measured with CCK-8 assays and flow cytometry.Cell migration and invasion ability were measured with Transwell assays.Multiplex bead-based assays were performed to identity the factors downstream of L1 CAM.Xenograft studies were performed in nude mice to evaluate the effects of L1 CAM on tumor growth and regulatory T cell(Treg)recruitment.Results:L1 CAM expression was significantly elevated in ESCC tissues(P<0.001)and correlated with poorer prognosis(P<0.05).Ablation of L1 CAM in ESCC cells inhibited tumor growth and migration,and increased tumor cell apoptosis(P<0.05).In the tumor microenvironment,L1 CAM expression correlated with Treg infiltration in ESCC by affecting CCL22 secretion.Mechanistically,L1 CAM facilitated CCL22 expression by activating the PI3 K/Akt/NF-κB signaling pathway.Furthermore,CCL22 promoted Treg recruitment to the tumor site;the Tregs then secreted TGF-β,which in turn promoted L1 CAM expression via Smad2/3 in a positive feedback loop.Conclusions:Our findings provide new insight into the mechanism of immune evasion mediated by L1 CAM,suggesting that targeting L1 CAM-CCL22-TGF-βcrosstalk between tumor cells and Tregs may offer a unique means to improve treatment of patients with ESCC.

High Performance Asymmetric Three Corrugation-Pitch-Modulated DFB Lasers Suitable for Stable Single Longitudinal Mode Operation

This paper presents an optimized asymmetric three corrugation-pitch-modulated DFB laser (3CPM-DFB) with extremely high mode selectivity(△αL= 0.97) and low flatness(F = 0.009), which are two key parameters to indicate the laser’s single longitudinal mode(SLM) performance. In threshold analysis, the optimization process based on transfer matrix method is demonstrated to maximize △αL?and minimize F simultaneously. In the above-threshold regime, the evolutions of △αL?and?longitudinal distribution of photon density with injection current are evaluated. More importantly, nanoimprint lithography which was proved an efficient way to fabricate DFB gratings can provide completely same simple fabrication procedure for both 3CPM grating and conventional uniform grating. So the big practical value of 3CPM-DFB can be expected because of its advanced performance and easy manufacturability.