A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Leveraging diverse cell-death patterns to predict the prognosis, immunotherapy and drug sensitivity of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) poses clinical challenges due to its varied prognosis, tumor microenvironment attributes, and responses to immunotherapy. We established a novel Programmed Cell Death-related Signature (PRS) for ccRCC assessment, derived through the Least Absolute Shrinkage and Selection Operator (LASSO) regression method. We validated PRS using the E-MTAB-1980 dataset and created PCD-related clusters via non-negative matrix factorization (NMF). Our investigation included an in-depth analysis of immune infiltration scores using various algorithms. Additionally, we integrated data from the Cancer Immunome Atlas (TCIA) for ccRCC immunotherapy insights and leveraged the Genomics of Drug Sensitivity in Cancer (GDSC) database to assess drug sensitivity models. We complemented our findings with single-cell sequencing data and employed the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and qRT-PCR to compare gene expression profiles between cancerous and paracancerous tissues. PRS serves as a valuable tool for prognostication, immune characterization, tumor mutation burden estimation, immunotherapy response prediction, and drug sensitivity assessment in ccRCC. We identify five genes with significant roles in cancer promotion and three genes with cancer-suppressive properties, further validated by qRT-PCR and CPTAC analyses, showcasing gene expression differences in ccRCC tissues. Our study introduces an innovative PCD model that amalgamates diverse cell death patterns to provide accurate predictions for clinical outcomes, mutational profiles, and immune characteristics in ccRCC. Our findings hold promise for advancing personalized treatment strategies in ccRCC patients.

Bridging the gap between clear cell renal cell carcinoma and cutaneous melanoma: the role of SCARB1 in dysregulated cholesterol metabolism.

OBJECTIVE: The metabolism of cholesterol has been found to be closely related to the proliferation, invasion, and metastasis of tumors. The purpose of this study was to investigate the correlation between cholesterol metabolic genes and the prognosis of clear cell renal cell carcinoma (ccRCC). METHODS: Gene expression profiles and clinical information of individuals diagnosed with prevalent malignant tumors were obtained from the TCGA database. For survival analysis, Kaplan-Meier curves were used. Consensus clustering was utilized to identify distinct molecular clusters. LASSO regression analysis was utilized to construct a novel prognostic signature. Differential analysis was used to analyze the differences in gene expression and various evaluation indicators between different subgroups. RT-qPCR and Immunohistochemistry were performed to examine the gene expression. Small interfering RNA transfection, CCK-8, and clone formation assays were conducted to verify the function of the target gene in ccRCC cell lines. RESULTS: Based on genes involved in cholesterol metabolism related to survival, two molecular ccRCC subtypes were identified with distinct clinical, immune, and biological features. A molecular signature which would be utilized to evaluate the prognosis and the immune status of the tumor microenvironment of ccRCC patients was also established. The SCARB1-mediated cholesterol-dependent metabolism occurred both in ccRCC and skin cutaneous melanoma. CONCLUSION: A gene signature related to cholesterol metabolism was developed and validated to forecast the prognosis of ccRCC, demonstrating a correlation with immune infiltration. Cholesterol metabolic genes such as SCARB1, were expected to contribute to the diagnosis and precision treatment of both ccRCC and skin cutaneous melanoma.

Combining single-cell and transcriptomic analysis revealed the immunomodulatory effect of GOT2 on a glutamine-dependent manner in cutaneous melanoma.

Background: Reprogramming in glutamine metabolism is a hallmark of cancers, while its role in cutaneous melanoma has not been studied at great length. Methods: Here, we constructed a glutamine metabolism-related prognostic signature in cutaneous melanoma with a variety of bioinformatics methods according to the glutamine metabolism regulatory molecules. Moreover, experimental verification was carried out for the key gene. Results: We have identified two subgroups of cutaneous melanoma patients, each with different prognoses, immune characteristics, and genetic mutations. GOT2 was the most concerned key gene among the model genes. We verified its role in promoting tumor cell proliferation by CCK-8 and clone formation assays. Conclusion: Our study cast new light on the prognosis of cutaneous melanoma, and the internal mechanism regulating glutamine metabolism of GOT2 may provide a new avenue for treating the cutaneous melanoma disease precisely.

Awakening Allies for Breaking Microenvironment Barriers: NIR-II Guided Orthogonal Activation of Tumor-Infiltrating Mast Cells for Efficient Nano-Drug Delivery.

Mast cells (MCs), powerful immune cells that heavily infiltrate cancer cells, play a crucial role in tumor formation. Activated MCs can release histamine and a family of proteases through degranulation effects, concurrently achieving endothelial junction weakening and stromal degradation of the tumor microenvironment, thereby clearing the obstacles for nano-drug infiltration. To achieve precise activation of tumor-infiltrating MCs, orthogonally excited rare earth nanoparticles (ORENP), with two channels, are introduced for the controllable stimulating drugs release wrapped in "photocut tape". The ORENP can emit near-infrared II (NIR-II) for image tracing for tumor localization in Channel 1 (808/NIR-II) and allows energy upconversion to emit ultraviolet (UV) light for releasing drugs for MCs stimulation in Channel 2 (980/UV). Finally, the combined use of chemical and cellular tools enables clinical nano-drugs to achieve a significant increase in tumor infiltration, thereby enhancing the efficacy of nano-chemotherapy.

Nomograms for predicting the prognosis of patients with penoscrotal extramammary Paget's disease: A retrospective study in the SEER database and two medical centers.

Background: Extramammary Paget' s disease (EMPD) is a rare cutaneous malignant tumor, and the prognostic factors associated with penoscrotal EMPD remains unclear. The purpose of this study is to investigate prognostic factors and construct nomograms to predict the outcome of patients with EMPD located in the penis or scrotum. Methods: From the Surveillance, Epidemiology and End Results (SEER) database, we extracted 95 patients with primary EMPD located in the penis or scrotum as the training cohort. Forty-nine penoscrotal EMPD patients were included from two medical centers as the external validation cohort. Univariate and multivariate Cox regression model were applied to investigating risk factors of cancer-specific survival (CSS) and overall survival (OS). Based on the results of multivariate Cox regression analysis, the nomograms were constructed for predicting CSS and OS of patients with penoscrotal EMPD. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were applied to evaluate the practicability and accuracy of the nomograms. Results: In the training cohort, multivariate Cox regression analysis showed that marital status and tumor stage were independent factors of CSS, and marital status, tumor stage and surgery are associated with OS independently in patients with penoscrotal EMPD. Based on these results, we developed nomograms to predict CSS and OS respectively. The C-index values were 0.778 for CSS, and 0.668 for OS in the training set, which displayed the good discriminations. In the external validation set, the C-index values were 0.945 for CSS, and 0.703 for OS. The areas under the curve (AUC) values of nomogram predicting 1-, 3-, and 5-year CSS were 0.815, 0.833, and 0.861 respectively, and 0.839, 0.654, and 0.667 for nomogram predicting 1-, 3-, and 5-year OS respectively. In the validation set, the AUC values of nomogram predicting 1-, 3-, and 5-year CSS were 0.944, 0.896, and 0.896 respectively, and 0.777, 0.762 and 0.692 for nomogram predicting 1-, 3-, and 5-year OS respectively. Additionally, the internal calibration curves also proved that our nomograms have good accuracy. Conclusions: By incorporating marital status, tumor stage and/or surgery, our nomograms can efficiently predict CSS and OS of patients with penoscrotal EMPD.

A comprehensive analysis on the relationship between BDE-209 exposure and erectile dysfunction.

Decabromodiphenyl ether (mainly BDE-209) is a commonly used brominated flame retardant in various industrial products. Although its damage to the reproduction system has been established, its effect on erectile function remains unclear. The present study investigated whether BDE-209 induced erectile dysfunction in male SD rats and the underlying mechanisms. Pubertal male rats were exposed to BDE-209 orally (0, 5, 50, and 500 mg/kg/day) for 28 days and the ICP (intracavernous pressure) and MAP (mean arterial pressure) were measured. After the rats were euthanized, the fibrosis and apoptosis levels were evaluated. Additionally, the endothelial function of the rat vascular endothelium cells and the human umbilical vein endothelial cells were impaired after treatment with 50 µM and 100 µM BDE-209. Moreover, the bioinformatics based on CTD database and ChIP-X Enrichment Analysis, version 3 (ChEA3) and molecular docking analysis demonstrated that 5 transcription factors (NFKB1, NR3C1, E2F5, REL, IRF4) might regulate endothelial function by affecting the expression of interactive genes (BCL-2, CAP3, CAT, TNF, MAPK1, and MAPK3). In summary, the present study demonstrated that BDE-209 might affect downstream interactive genes by binding to transcription factors, leading to corpus cavernosum endothelial dysfunction, thus contributing to erectile dysfunction in rats.

The involvement of ERK1/2 and p38 MAPK in the premature senescence of melanocytes induced by H2O2 through a p53-independent p21 pathway.

BACKGROUND: The pathogenesis of vitiligo is still unknown and oxidative stress is an important factor that can damage or incapacitate melanocytes. OBJECTIVE: To investigate the role of oxidative stress in the premature senescence of melanocytes and their transfer of melanosomes. METHODS: Cultured human melanocytes were treated with H2O2 after which cell viability and apoptosis were assessed. We investigated whether exposure to H2O2 induces premature senescence. RNA sequencing was used to screen aging-related signaling pathways. The expression of dendritic regulatory proteins, adhesion molecules and cell cytoskeletal proteins, as well as melanosome distribution were characterized. The ROS scavenger NAC was used to study the role of ROS in cell senescence and in melanosome transfer. RESULTS: Cell viability decreased progressively and cell apoptosis increased after treatment with H2O2. H2O2 treatment tended to induce premature senescence in melanocytes through a p53-independent p21 pathway. RNA sequencing analysis showed that H2O2 treatment induced the differential expression of MAPK signaling pathway components. Western blotting and qRT-PCR confirmed that H2O2 treatment increased the phosphorylation of ERK1/2 and p38 MAPK, which are involved in inducing the senescence of melanocytes, but not JNK. The expression of cell cytoskeleton and adhesion molecules decreased after H2O2 treatment. p21 siRNA treatment reversed these changes. Treatment with NAC improved the premature senescence and the impaired melanosome transfer induced by H2O2. CONCLUSION: H2O2 increases ROS levels, which activates the ERK1/2 and p38 MAPK pathways to induce the premature senescence of melanocytes through p21 via a p53-independent pathway and consequently disrupts melanosome transfer.

A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration.

BACKGROUND: Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. METHODS: According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. RESULTS: Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. CONCLUSIONS: Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCA patients.

Age-Related Differences in Molecular Profiles for Immune Checkpoint Blockade Therapy.

Immune checkpoint blockade (ICB) therapies have significantly improved the prognosis and shown considerable promise for cancer therapy; however, differences in ICB treatment efficacy between the elderly and young are unknown. We analyzed the studies enrolled in the meta-analysis using the deft approach, and found no difference in efficacy except melanoma patients receiving anti-PD-1 therapy. Similarly, higher treatment response rate and more favorable prognosis were observed in elderly patients in some cancer types (e.g., melanoma) with data from published ICB treatment clinical trials. In addition, we comprehensively compared immunotherapy-related molecular profiles between elderly and young patients from public trials and The Cancer Genome Atlas (TCGA), and validated these findings in several independent datasets. We discovered a divergent age-biased immune profiling, including the properties of tumors (e.g., tumor mutation load) and immune features (e.g., immune cells), in a pancancer setting across 27 cancer types. We believe that ICB treatment efficacy might vary depending on specific cancer types and be determined by both the tumor internal features and external immune microenvironment. Considering the high mutational properties in elderly patients in many cancer types, modulating immune function could be beneficial to immunotherapy in the elderly, which requires further investigation.

Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats.

Di-n-butyl phthalate (DBP) is a widely used plasticizer and an environmental endocrine-disrupting compound. However, whether prenatal exposure to DBP can impair erectile function remains unknown. We conducted this study to investigate the potential effects of prenatal exposure to DBP on erectile function and the underlying mechanisms. A rat model of prenatal DBP exposure (12.5, 100 or 800 mg/kg/day by gavage during gestational days 13-21) was established. Prenatal DBP exposure significantly decreased penis/body weight ratio, myelin sheath thickness of cavernosum nerves and serum testosterone level in male rats at the age of 10 weeks. Furthermore, erectile dysfunction was detected in all DBP exposure groups, which exhibited substantial increases in transforming growth factor-ß1 (TGF-ß1) expression and decreases in the expression of alpha smooth muscle actin (α-SMA), neuronal and endothelial nitric oxide synthase (nNOS and eNOS). Additionally, the phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratio and caspase-3 were higher in DBP exposure groups than in the control group. Notably, prenatal exposure to DBP increase the risk of ED in male adult rats, even taking low dose of DBP (12.5 mg/kg/day). DBP exposure causing penile fibrosis, decreased testosterone level, and endothelial dysfunction may be responsible for ED by activating Akt/Bad/Bax/caspase-3 pathway and suppressing NOS/cGMP pathway in penis.

Malignant Evaluation and Clinical Prognostic Values of M6A RNA Methylation Regulators in Prostate Cancer.

Objective: M6A RNA modification is closely associated with tumor genesis and progression of several malignancies; however, its role in prostate cancer (PCa) remains poorly understood. Materials and methods: Expression data and corresponding clinicopathologic information were available freely from the Cancer Genome Atlas (TCGA) dataset. We compared the expression level of m6A RNA methylation regulators in PCa with different clinicopathologic characteristics and identified subgroups based on their expressions with consensus clustering. To build the signature and assess its prognostic value, several methods were used for the analysis, including univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, time-dependent receiver operating curve (ROC), and Kaplan-Meier (KM) survival analysis. Results: Most of the m6A RNA methylation regulators were differentially expressed not only between normal and tumor tissue but also among PCa stratified by different clinicopathologic characteristics. There were obvious differences between two clusters, cluster 1 and 2, regarding clinicopathologic features, and the recurrence-free survival (RFS) in cluster 2 was significantly worse than cluster 1. We developed an eleven-gene signature which exhibited a high prognostic value and was able to independently predict RFS. Moreover, a nomogram which integrated clinical information and the gene signature was capable of distinguishing high-risk recurrent patients. Conclusion: These methylation regulators are correlated to clinicopathologic characteristics in PCa and a prognostic model using m6A methylation-related genes is constructed and of high predictive value for recurrence after RP.

Identification and validation of a six immune-related gene signature for prediction of biochemical recurrence in localized prostate cancer following radical prostatectomy.

BACKGROUND: Prostate cancer (PCa) is the second lethal heterogeneous cancer among males worldwide, and approximately 20% of PCa patients following radical prostatectomy (RP) will undergo biochemical recurrence (BCR). This study is aimed to identify the immune-related gene signature that can predict BCR in localized PCa following RP. METHODS: Expression profile of genes together with clinical parameters from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GEO) and the immune-related genes from the Molecular Signatures Database v4.0 were applied to construct and validate the gene signature. The Cox regression analyses were conducted to identify the candidate genes and establish the gene signature. To estimate the prognostic power of the risk score, the time-dependent receiver operating characteristic (ROC) analysis and Harrell's index of concordance (C-index) were utilized. We also established a nomogram to forecast the probability of patients' survival. RESULTS: A total of 268 patients from the TCGA and 77 patients from GSE70770 and six immune-related genes (SCIN, THY1, TBX1, NOTCH4, MAL, BNIP3L) were eventually selected. The Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer recurrence-free survival (RFS) compared to those in the high-risk group. In the multivariate Cox model, the signature was identified as an independent prognostic factor, which was significantly associated with RFS (TCGA: HR =5.232, 95% CI: 1.762-15.538, P=0.003; GSE70770: HR =2.158, 95% CI: 1.051-4.432, P=0.036). Moreover, the C-index got improved after incorporating the risk score into original clinicopathological parameters. In addition, the novel nomogram was constructed to better predict the 1-, 3- and 5-year RFS. CONCLUSIONS: This signature could serve as an independent prognostic factor for BCR. Incorporation of our signature into traditional risk classification might further stratify patients with different prognosis, which could assist practitioners in developing clinical decision-making.

The Identification and Validation of a Robust Immune-Associated Gene Signature in Cutaneous Melanoma.

BACKGROUND: Cutaneous melanoma is defined as one of the most aggressive skin tumors in the world. An increasing body of evidence suggested an indispensable association between immune-associated gene (IAG) signature and melanoma. This article is aimed at formulating an IAG signature to estimate prognosis of melanoma. METHODS: 434 melanoma patients were extracted from The Cancer Genome Atlas (TCGA) database, and 1811 IAGs were downloaded from the ImmPort database in our retrospective study. The Cox regression analysis and LASSO regression analysis were utilized to establish a prognostic IAG signature. The Kaplan-Meier (KM) survival analysis was performed, and the time-dependent receiver operating characteristic curve (ROC) analysis was further applied to assess the predictive value. Besides, the propensity score algorithm was utilized to balance the confounding clinical factors between the high- and low-risk groups. RESULTS: A total of six prognostic IAGs comprising of INHA, NDRG1, IFITM1, LHB, GBP2, and CCL8 were eventually filtered out. According to the KM survival analysis, the results displayed a shorter overall survival (OS) in the high-risk group compared to the low-risk group. In the multivariate Cox model, the gene signature was testified as a remarkable prognostic factor (HR = 45.423, P < 0.001). Additionally, the ROC curve analyses were performed which demonstrated our IAG signature was superior to four known biomarkers mentioned in the study. Moreover, the IAG signature was significantly related to immunotherapy-related biomarkers. CONCLUSION: Our study demonstrated that the six IAG signature played a critical role in the prognosis and immunotherapy of melanoma, which might help clinicians predict patients' survival and provide individualized treatment.

A Novel Apoptosis-Related Gene Signature Predicts Biochemical Recurrence of Localized Prostate Cancer After Radical Prostatectomy.

Background: Nowadays, predictions of biochemical recurrence (BCR) in localized prostate cancer (PCa) patients after radical prostatectomy (RP) are mainly based on clinical parameters with a low predictive accuracy. Given the critical role of apoptosis in PCa occurrence and progression, we aimed to establish a novel predictive model based on apoptosis-related gene signature and clinicopathological parameters that can improve risk stratification for BCR and assist in clinical decision-making. Methods: Expression data and corresponding clinical information were obtained from four public cohorts, one from The Cancer Genome Atlas (TCGA) dataset and three from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis (WGCNA) was performed to identify candidate modules closely correlated to BCR, and univariate and multivariate Cox regression analyses were utilized to build the gene signature. Time-dependent receiver operating curve (ROC) and Kaplan-Meier (KM) survival analysis were used to assess the prognostic value. Finally, we analyzed the expression of genes in the signature and validated the results using quantitative real-time PCR (qRT-PCR). Results: The novel gene signature we established exhibited a high prognostic value and was able to act as an independent risk factor for BCR [Training set: P < 0.001, hazard ratio (HR) = 7.826; Validation set I: P = 0.006, HR = 2.655; Validation set II: P = 0.003, HR = 4.175; Validation set III: P < 0.001, HR = 3.008]. Nomogram based on the gene signature and clinical parameters was capable of distinguishing high-risk BCR patients. Additionally, functional enrichment analysis showed several enriched pathways and biological processes, which might help reveal the underlying mechanism. The expression results of qRT-PCR were consistent with TCGA results. Conclusion: The apoptosis-related gene signature could serve as a powerful predictor and risk factor for BCR in localized PCa patients after RP.

A twelve-gene signature for survival prediction in malignant melanoma patients.

BACKGROUND: Melanoma is defined as a highly mutational heterogeneous disease containing numerous alternations of the molecule. However, due to the phenotypically and genetically heterogeneity of malignant melanoma, conventional clinical characteristics remain restricted or limited in the ability to accurately predict individual outcomes and survival. This study aimed to establish an accurate gene expression signature to predict melanoma prognosis. METHODS: In this study, we established an RNA sequencing-based 12-gene signature data of melanoma patients obtained from 2 independent databases: the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. We evaluated the quality of each gene to predict survival conditions in each database by employing univariate and multivariate regression models. A prognostic risk score based on a prognostic signature was determined. This prognostic gene signature further classified patients into low-risk and high-risk groups. RESULTS: Based on a prognostic signature, a prognostic risk score was determined. This prognostic gene signature further divided the patients into low-risk and high-risk groups. In the chemotherapy and radiotherapy groups of the TCGA cohort and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) expression group in the GEO cohort, patients in the low-risk group had a longer survival duration compared to patients in the high-risk group. Nevertheless, the immunotherapy group in the TCGA database and neuroblastoma RAS viral oncogene homolog (NRAS) expression group in the GEO database had no significant differences in statistics. Moreover, this gene signature was associated with patient prognosis regardless of whether the Breslow depth was greater than or less than 3.75 mm. Stratified gene set enrichment analysis (GSEA) revealed that certain immune-related pathways, such as the T-cell signaling pathway, chemokine signaling pathway, and primary immunodeficiency, were significantly enriched in the low-risk group of both TCGA and GEO cohorts. This information implied the immune-related properties of the 12-gene signature. CONCLUSIONS: Our study emphasizes the significance of the gene expression signature in that it may be an indispensable prognostic predictor in melanoma and has great potential for application in personalized treatment.

Nomograms to predict the presence and extent of inguinal lymph node metastasis in penile cancer patients with clinically positive lymph nodes.

BACKGROUND: We developed two nomograms to predict the presence of inguinal lymph node metastasis (ILNM) and two or more histologically positive inguinal lymph nodes (ILNs) or one ILN with extranodal extension (ENE) in penile cancer patients with clinically positive inguinal lymph nodes (ILNs). METHODS: This study enrolled 75 penile squamous cell carcinoma (PSCC) patients with clinically positive ILNs. A binary logistic regression model was taken to screen out the risk factors for the presence of ILNM and two or more positive ILNs or one node with ENE in one side. Nomograms were plotted based on the results of multivariate logistic regression analysis. RESULTS: Our multivariate analysis demonstrated that the pathological grade, lymphovascular invasion (LVI), and short diameter (SD) of the largest ILN were independent risks. The bootstrap-corrected concordance index of the nomogram for the presence of ILNM was 0.948, and 0.878 for two or more histologically positive ILNs or one ILN with ENE on one side. CONCLUSIONS: By incorporating tumor pathological grade, LVI and SD of the largest ILN, our nomograms can efficiently predict the ILNM in penile cancer patients with clinically positive nodes.

m6A RNA methylation regulators correlate with malignant progression and have potential predictive values in clear cell renal cell carcinoma.

N6-methyladenosine (m6A) has been reported to be involved in several biological processes in tumors. In this study, we found that most of the m6A RNA methylation regulators were not only differentially expressed between clear cell renal cell carcinoma (ccRCC) and normal but also among ccRCC stratified by different clinicopathologic characters. Two ccRCC subgroups, cluster 1 and 2, were identified using consensus clustering based on the expression of m6A methylation regulators. Although no obvious differences were observed between two subgroups regarding clinicopathologic characters, except gender, patients in cluster 1 had a relatively more favorable survival rate than cluster 2. Moreover, we established a risk signature with two m6A methylation regulators, METTL3 and METTL14, which was not only of great value for prognosis prediction but also closely associated with clinicopathological features. In conclusion, m6A RNA methylation regulators play an important role in ccRCC progression and are potentially favorable for prognostic stratification.

The risks of cancer development in systemic lupus erythematosus (SLE) patients: a systematic review and meta-analysis.

BACKGROUND: Although accumulating data have suggested the development of cancer in systemic lupus erythematosus (SLE) patients, these results remain inconsistent. To examine such a putative association, this analysis reports the association between SLE and the risks of 24 cancer types. METHODS: Online databases PubMed, EMBASE, and Web of Science were searched comprehensively for eligible studies, published up to 15 May 2018. Pooled standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were utilized to reveal their associations. RESULTS: A total of 24 eligible studies were ultimately enrolled. Our results indicated that SLE was associated with increased risk of overall cancers, cancer risk in both genders, non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia, multiple myeloma, cervix, vagina/vulva, renal, bladder, esophagus, gastric, hepatobiliary, lung, oropharynx, larynx, non-melanoma skin, and thyroid cancers. Additionally, SLE could reduce the risk of prostate cancer and cutaneous melanoma; however, it was not significantly associated with breast, uterus, ovarian, pancreatic, colorectal, or brain cancers. CONCLUSIONS: Our results shed light SLE being correlated with increased risk for 16 involved cancers and decreased risk for prostate cancer and cutaneous melanoma. This comprehensive meta-analysis provides epidemiological evidence supporting the associations between SLE and cancer risk. This evidence could be utilized to drive public policies and to help guide personalized medicine to better manage SLE and reduce associated cancer morbidity and mortality.

[Effects of Xialiqi Capsules on the expressions of PCNA and caspase-3 in rats withbenign prostatic hyperplasia].

OBJECTIVE: To explore the effects of Xialiqi Capsules(XLQ) on the expressions of the proliferating cell nuclear antigen (PCNA) and caspase-3 in the prostate tissue of the BPH rat model. METHODS: Fifty male SD ratswereequally randomized into groups A (sham operation control), B (BPH model control), C (high-dose XLQ), D (low-dose XLQ), and E (finasteridecontrol) andthe BPH modelswere established by subcutaneous injection of testosterone propionate at 0.5 mg per kilogram of the body weight per day for 30 days after castration. After modeling, the animals in groups A and B were treated intragastricallywith normal saline, while those in C, D, and E with XLQ at 1.20 and 0.61 g per kilogram of the body weight per day or finasterideat 0.8 mg per kilogram of the body weight per day, respectively, all for 30 days. Then,the bilateral prostates were harvestedfrom the rats for calculation of the prostatic index (prostate wet weight/ body weight) and determination of the expressions of PCNA and caspase-3 in the prostate tissue by immunohistochemistry and immunofluorescence staining, respectively. RESULTS: The prostate wet weight and prostate index were significantly increased in group B as compared with group A, (ï¼»1326±60ï¼½ vsï¼»471±17ï¼½ g, P<0.01; ï¼»2.89±0.18ï¼½ vs ï¼»1.06±0.06ï¼½ mg/g, P<0.01), but decreased in groups C (ï¼»914±36ï¼½ g;ï¼»2.02±0.08ï¼½ mg/g), D (ï¼»1 099±46ï¼½g;ï¼»2.39±0.11ï¼½ mg/g), and E (ï¼»817±53ï¼½ g;ï¼»1.83±0.10ï¼½ mg/g)in comparison with B (P<0.01), with statistically significant differences among groups C, D, and E(P<0.01) and most significantly in E.The PCNA level in the prostate tissue wasremarkably higher in group B than in A, but lower in groups C, D and E than in B. The expression of caspase-3 was down-regulatedin group B as compared with A, but up-regulated in groups C, D and E in comparison with B, most significantly in E. CONCLUSIONS: Xialiqi Capsules can effectively reduce the prostate wet weight and prostatic index of in rats with BPH by inhibiting the level of PCNA and promoting the expression of caspase-3.