Vph2 is required for protection against a reductive stress in Candida albicans.

Vph2 is a putative V-ATPase assembly factor. Our previous study has characterized its roles in localization of V-ATPase subunit, cell wall composition, hyphal development and virulence. In this study, our results further demonstrated that Vph2 was localized around the nucleus and in patches close to the periphery of the cell, indicating that Vph2 was located to the endoplasmic reticulum (ER), which was consistent with that in Saccharomyces cerevisiae. Disruption of VPH2 led to hypersensitivity to reducing stresses induced by dithiothreitol (DTT) and ß-mercaptoethanol (ß-ME), and displayed increased GSH content and up-regulation of unfolded protein response (UPR)-related genes, such as PRB1 and PMT4. However, the induced UPR and growth defect on ß-ME plates of vph2Δ/Δ mutant could be partly alleviated by the GSH-specific scavenger 1-chloro-2, 4-dinitrobenzene (CDNB). These results indicated that loss of VPH2 led to an increase in GSH levels, which induced the UPR and caused the defective growth on reductive stress induced by ß-ME. In summary, Vph2 is necessary to maintain resistance against reductive stresses.

Photodynamic Therapy Combined with Liquid Nitrogen Cryotherapy and Curettage for the Treatment of Recalcitrant Periungual and Subungual Warts: Clinical Experience and Literature Review.

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

KMT2C is a Potential Biomarker of Anti-PD-1 Treatment Response in Metastatic Melanoma.

BACKGROUND: Metastatic melanoma (MM) represents a common malignancy with poor prognosis. Immune checkpoint inhibition (ICI), including PD-1 blockade, has been emerging as the popular therapeutic in MM for its durable treatment effect, but its response rate is still limiting. METHODS: We comprehensively analyzed the associations between KMT2C somatic mutation and the tumor microenvironment as well as the ICI response of MM patients based on three published cohorts. Gene differential expression analysis between tumor samples with mutated and wild-type KMT2C was performed by DESeq2 package. Functional enrichment analysis was conducted by using clusterProfiler package. Kaplan-Meier was used to perform overall survival probability estimate through survival package and rms package was applied for the construction of nomogram model. RESULTS: We report here that KMT2C is a potential biomarker for anti-PD-1 treatment in MM. This biomarker can be used for comprehensively analyzing its association with patients' prognosis, tumor microenvironment and genomic features. Mutations of KMT2C profoundly altered expression of immune- and DNA replication-related genes in MM tumors. MM patients harboring KMT2C mutations showed significantly better overall survival (OS) after treatment with PD-1 monoclonal antibody as compared to wild-type KMT2C. Although KMT2C mutation has no significant influence on immune cell infiltration into MM tumors, the tumor mutation load and neoantigen load are indeed elevated in KMT2C mutated MM samples. This might represent a possible pathway through which KMT2C regulates the response of MM patients to anti-PD-1 treatment. Finally, we constructed a nomogram model by combing the independent prognostic factors, including KMT2C mutation, which could effectively predict the 1-year survival probability of MM patients after anti-PD-1 treatment. CONCLUSIONS: In conclusion, we report the role of KMT2C in anti-PD-1 treatment response regulation in MM for the first time. This may consequently be helpful for KMT2C personalized application.

CEBPB is associated with active tumor immune environment and favorable prognosis of metastatic skin cutaneous melanoma.

Metastatic skin cutaneous melanoma (SKCM) is a common malignancy that accounts for low morbidity but high mortality of skin cancer. SKCM is characterized by high lymphocytic infiltration, whereas the states of infiltrated cells are variable in patients leading to a heterogeneous prognosis and hindering appropriate clinical decisions. It is therefore urgent to identify markers associated with lymphocytic infiltration, cellular conditions, and the prognosis of SKCM. In this study, we report that CEBPB, a transcriptional factor, is mainly expressed in macrophages in metastatic SKCM and associated with an active tumor immune environment and a favorable prognosis through integrated analysis of single-cell and bulk RNA-seq datasets. High CEBPB expression is significantly associated with active inflammation and immune response pathways in both macrophages and bulk SKCM tumor tissues. A signature based on CEBPB-associated genes that are specifically expressed in macrophages could robustly and prognostically separate different metastatic SKCM patients. In addition, the associations between the metastatic SKCM tumor signature and microenvironment with respect to T-cell recruitment and state, inflammation response, angiogenesis, and so on were also determined. In conclusion, we present here the first report on CEBPB in tumor immune environment and prognosis regulation in metastatic SKCM and construct a reliable signature, which should provide a useful biomarker for stratification of the patient's prognosis and therapeutic selection.

Comprehensive Analysis of Chromatin Accessibility and Transcriptional Landscape Identified BRCA1 Repression as a Potential Pathological Factor for Keloid.

Keloid is a poorly understood fibrotic skin disease that commonly occurs during wound-healing. As a polymer composed of nucleic acid and proteins, the structure of chromatin could be dynamically regulated in the nucleus. In this study, we explored the dynamics of chromatin accessibility and the transcriptome in dermal fibroblasts (DFs) in keloid formation. Compared to normal samples, chromatin accessibility and transcriptome were extensively altered in keloid DFs. In addition, changes in chromatin accessibility were closely associated with changes in gene expression in DFs. Breast cancer type 1 (BRCA1) was significantly downregulated in keloid DFs, and its knockdown promoted the proliferation and attenuated the migration ability of normal DF cells. Mechanistically, BRCA1 suppression significantly reduced the expression of neuronal pentraxin 2 (NPTX2), a cell viability-related gene. BRCA1 binding affinity at the NPTX2 enhancer and the chromatin accessibility in the same region were significantly lower in keloid DFs than in normal DFs, which might contribute to NPTX2 inhibition. In conclusion, this study identified BRCA1 inhibition in DFs as a novel pathological factor in keloids and preliminarily explored its potential mechanisms, which will help us understand the formation of keloids.

Elevated KLF7 levels may serve as a prognostic signature and might contribute to progression of squamous carcinoma.

Global efforts have been undertaken to define the genome-wide distribution of epigenetic markers in cancerous tissues, which provide an invaluable opportunity to understand cancer biology and identify predictive signatures. Several studies have focused on the gene expression patterns of squamous carcinoma to identify tumor subtypes and find prognostic and therapeutic targets because squamous carcinoma genomes showed high instability. However, the number of reliable reports referring prognostic significance of genes and their role in squamous carcinoma is still quite limited. Krüppel-like factor 7 (KLF7) is a transcription factor that is widely expressed in numerous human tissues at low levels. Members of the KLF family have established roles in tumor cell fate, stress response, cell survival and the tumor-initiating properties of cancer stem-like cells. Hence to investigate whether KFL7 expression from cancer tissue holds promise as a prognostic and/or therapeutic target, we analyzed gene expression profiles from squamous carcinoma and surgical margin tissues in The Cancer Genome Atlas. We identified significant up-regulation of KLF7 in squamous carcinoma, which was confirmed by immunohistochemical staining. Elevated KLF7 expression was associated with poor squamous carcinoma prognosis before and after correcting for confounding factors by multivariate Cox regression analysis. Several pathways, such as Neurotrophin and GnRH pathways, were activated in KLF7-up-regulated squamous carcinoma samples through Gene Set Enrichment Analysis. In conclusion, we consolidate the potential role(s) of KLF7 in squamous carcinoma carcinogenesis from The Cancer Genome Atlas surgical margin tissue, offering insights into expression signatures that are potentially useful for prognosis modalities.

Immune-related genes have prognostic significance in head and neck squamous cell carcinoma.

AIMS: Head and neck squamous cell carcinoma (HNSCC) is an highly aggressive tumor with heterogeneous prognosis. We here report that immune-related genes (IRGs) could effectively distinguish prognostically different HNSCC patients. MATERIALS AND METHODS: MRNA levels of 1333 IRGs that from ImmPort database in HNSCC samples were acquired from the Cancer Genome Atlas (TCGA). H2o, a machine learning-based R package, was used for screening the top most representative genes from the IRGs. Univariate Cox-regression analysis was performed to identify prognostically-related genes based on the randomly generated training samples from TCGA set. LASSO Cox-regression analysis was applied for the construction of prognostic model for HNSCC. A total of six IRGs were finally retained for their prognostic significance and used for LASSO Cox-regression analysis. KEY FINDINGS: Samples from exclusive training and testing set that randomly generated from TCGA, and another independent validation set from the Gene Expression Omnibus (GEO) were divided into high- and low-risk groups according to the prognostic model. HNSCC samples within high-risk groups have significantly inferior overall survival (OS) compared with those within low-risk groups. Differences in genomic mutation landscape and tumor infiltration immune cells also exist between the two sample groups. What's more, risk score was proved to be an independent prognostic factor for HNSCC by stratification analysis. SIGNIFICANCE: IRGs are pivotal HNSCC prognostic signatures and should be helpful for its clinical decision-making.

Identification of key pathways and genes in psoriasis via gene microarray analysis.

Psoriasis is a common chronic inflammatory, immune-mediated skin disease with a high incidence worldwide. It is a multifactorial disease and its exact pathogenesis has remained largely elusive. The purpose of the present study was to uncover the key pathways and genes associated with the incidence of psoriasis. Gene expression profiles (dataset no. GSE13355) were downloaded from Gene Expression Omnibus. Differentially expressed genes between skin samples from patients with lesional psoriasis or non­lesional psoriasis and those of normal healthy controls were identified using Bioconductor version 2.13 based in R. Kyoto Encyclopedia of Genes and genomes (KEGG) pathways significantly enriched in patients with lesional psoriasis were identified using gene set enrichment analysis (GSEA). Key KEGG pathways were then identified using leading-edge analysis of the results of GSEA. Differentially expressed genes involved in the significantly enriched KEGG pathways were considered as key genes. Several KEGG pathways which are known to be associated with lesional psoriasis, including autoimmune thyroid disease signaling, natural killer cell-mediated cytotoxicity signaling, as well as several novel pathways, including FCγR-mediated phagocytosis and neurotrophin signaling pathway, were identified. Several verified and novel genes were also got. The present study revealed key pathways and genes associated with psoriasis, which may serve as important biomarkers for the diagnosis and treatment of psoriasis.