Clustering and machine learning-based integration identify cancer associated fibroblasts genes’ signature in head and neck squamous cell carcinoma

Background: A hallmark signature of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) is abundantly infiltration of cancer-associated fibroblasts (CAFs), which facilitate HNSCC progression. However, some clinical trials showed targeted CAFs ended in failure, even accelerated cancer progression. Therefore, comprehensive exploration of CAFs should solve the shortcoming and facilitate the CAFs targeted therapies for HNSCC.Methods: In this study, we identified two CAFs gene expression patterns and performed the single‐sample gene set enrichment analysis (ssGSEA) to quantify the expression and construct score system. We used multi-methods to reveal the potential mechanisms of CAFs carcinogenesis progression. Finally, we integrated 10 machine learning algorithms and 107 algorithm combinations to construct most accurate and stable risk model. The machine learning algorithms contained random survival forest (RSF), elastic network (Enet), Lasso, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox (plsRcox), supervised principal components (SuperPC), generalised boosted regression modelling (GBM), and survival support vector machine (survival-SVM).Results: There are two clusters present with distinct CAFs genes pattern. Compared to the low CafS group, the high CafS group was associated with significant immunosuppression, poor prognosis, and increased prospect of HPV negative. Patients with high CafS also underwent the abundant enrichment of carcinogenic signaling pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation. The MDK and NAMPT ligand–receptor cellular crosstalk between the cancer associated fibroblasts and other cell clusters may mechanistically cause immune escape. Moreover, the random survival forest prognostic model that was developed from 107 machine learning algorithm combinations could most accurately classify HNSCC patients.Conclusion: We revealed that CAFs would cause the activation of some carcinogenesis pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation and revealed unique possibilities to target glycolysis pathways to enhance CAFs targeted therapy. We developed an unprecedentedly stable and powerful risk score for assessing the prognosis. Our study contributes to the understanding of the CAFs microenvironment complexity in patients with head and neck squamous cell carcinoma and serves as a basis for future in-depth CAFs gene clinical exploration

Analysis of ceRNA network of differentially expressed genes in FaDu cell line and a cisplatin-resistant line derived from it

Background Hypopharyngeal cancer accounts for 2% in head and neck cancers and has a poor prognosis. Cisplatin is a widely used chemotherapeutic drug in kinds of carcinomas, concluding hypopharyngeal cancer. However, the resistance of cisplatin appeared in recent years. Cisplatin-resistance has been partly explored before, but rarely in hypopharyngeal cancer. Methods We cultured the hypopharyngeal cancer cell (FaDu) and induced its cisplatin-resistant cell (FaDu/DDP4). Then we tested the differentially expressed genes (DEGs) between FaDu and FaDu/DDP4. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on the DEGs, and we drew the ceRNA networks of DEGs. Finally, we chose eight miRNAs and six mRNAs for qRT-PCR to verify our microarray. Results We induced cisplatin-resistant FaDu/DDP4 and proved its chemoresistance. The resistance index (RI) of FaDu/DDP4 was 2.828. DEGs contain 2,388 lncRNAs, 1,932 circRNAs, 745 mRNAs and 202 miRNAs. These 745 mRNAs were classified into three domains and 47 secondary GO terms. In KEGG pathway enrichment, the “TNF signaling pathway”, “IL-17 signaling pathway” and “JAK-STAT signaling pathway” were potentially significant signaling pathways. Then, 52 lncRNAs, 148 circRNAs, 155 mRNAs and 18 miRNAs were selected to draw the network. We noticed several potential targets (as miR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1). At last, the eight miRNAs and six mRNAs that are critical RNAs in ceRNA network were verified by qRT-PCR. Conclusion The microarray helped to find DEGs in cisplatin-resistant hypopharyngeal cancer. TNF, IL-17 and JAK-STAT signaling pathways might be more significant for cisplatin-resistance. MiR-197-5p, miR-6808-5p, APOE, MMP1, S100A9 and CYP24A1 might be potential genes inducing resistance

Tailoring Dzyaloshinskii-Moriya interaction in a transition metal dichalcogenide by dual-intercalation

Dzyaloshinskii-Moriya interaction (DMI) is vital to form various chiral spin textures, novel behaviors of magnons and permits their potential applications in energy-efficient spintronic devices. Here, we realize a sizable bulk DMI in a transition metal dichalcogenide (TMD) 2H-TaS2 by intercalating Fe atoms, which form the chiral supercells with broken spatial inversion symmetry and also act as the source of magnetic orderings. Using a newly developed protonic gate technology, gate-controlled protons intercalation could further change the carrier density and intensely tune DMI via the Ruderman-Kittel-Kasuya-Yosida mechanism. The resultant giant topological Hall resistivity of 1.4 uohm.cm at -5.2V (about 460% of the zero-bias value) is larger than most of the known magnetic materials. Theoretical analysis indicates that such a large topological Hall effect originates from the two-dimensional Bloch-type chiral spin textures stabilized by DMI, while the large anomalous Hall effect comes from the gapped Dirac nodal lines by spin-orbit interaction. Dual-intercalation in 2HTaS2 provides a model system to reveal the nature of DMI in the large family of TMDs and a promising way of gate tuning of DMI, which further enables an electrical control of the chiral spin textures and related electromagnetic phenomena.Comment: 21 pages, 4 figure

Near-infrared photoactivatable control of Ca signaling and optogenetic immunomodulation

The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed Opto-CRAC ) that selectively and remotely controls Ca2+ oscillations and Ca2+-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca2+-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded photoactivatable adjuvant to improve antigen-specific immune responses to specifically destruct tumor cells. Our study represents a solid step forward towards the goal of achieving remote control of Ca2+-modulated activities with tailored function

Room temperature magnetic phase transition in an electrically-tuned van der Waals ferromagnet

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room-temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr1.2Te2 observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8 * 10^21 cm^-3. We observed non-monotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr1.2Te2. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr1.2Te2 is a significant step towards practical spintronic devices.Comment: 18 pages, 4 figure