Predicting immunotherapy response in melanoma using a novel tumor immunological phenotype-related gene index.

Introduction: Melanoma is a highly aggressive and recurrent form of skin cancer, posing challenges in prognosis and therapy prediction. Methods: In this study, we developed a novel TIPRGPI consisting of 20 genes using Univariate Cox regression and the LASSO algorithm. The high and low-risk groups based on TIPRGPI exhibited distinct mutation profiles, hallmark pathways, and immune cell infiltration in the tumor microenvironment. Results: Notably, significant differences in tumor immunogenicity and TIDE were observed between the risk groups, suggesting a better response to immune checkpoint blockade therapy in the low-TIPRGPI group. Additionally, molecular docking predicted 10 potential drugs that bind to the core target, PTPRC, of the TIPRGPI signature. Discussion: Our findings highlight the reliability of TIPRGPI as a prognostic signature and its potential application in risk classification, immunotherapy response prediction, and drug candidate identification for melanoma treatment. The "TIP genes" guided strategy presented in this study may have implications beyond melanoma and could be applied to other cancer types.

miRSNP rs188493331: A key player in genetic control of microRNA-induced pathway activation in hypertrophic scars and keloids.

BACKGROUND: Our study aims to delineate the miRSNP-microRNA-gene-pathway interactions in the context of hypertrophic scars (HS) and keloids. MATERIALS AND METHODS: We performed a computational biology study involving differential expression analysis to identify genes and their mRNAs in HS and keloid tissues compared to normal skin, identifying key hub genes and enriching their functional roles, comprehensively analyzing microRNA-target genes and related signaling pathways through bioinformatics, identifying MiRSNPs, and constructing a pathway-based network to illustrate miRSNP-miRNA-gene-signaling pathway interactions. RESULTS: Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-ß, PI3K/Akt, and EGFR tyrosine kinase inhibitor resistance. Particularly noteworthy was the substantial crosstalk between the focal adhesion and PI3K/Akt signaling pathways, making them more susceptible to regulation by microRNAs. We also identified specific miRNAs, including miRNA-1279, miRNA-429, and miRNA-302e, which harbored multiple SNP loci, with miRSNPs rs188493331 and rs78979933 exerting control over a significant number of miRNA target genes. Furthermore, we observed that miRSNP rs188493331 shared a location with microRNA302e, microRNA202a-3p, and microRNA20b-5p, and these three microRNAs collectively targeted the gene LAMA3, which is integral to the focal adhesion signaling pathway. CONCLUSIONS: The study successfully unveils the complex interactions between miRSNPs, miRNAs, genes, and signaling pathways, shedding light on the genetic factors contributing to HS and keloid formation.

An advanced comprehensive muti-cell-type-specific model for predicting anti-PD-1 therapeutic effect in melanoma.

Rationale: Immune checkpoint inhibitors targeting the programmed cell death (PD)-1/PD-L1 pathway have promise in patients with advanced melanoma. However, drug resistance usually results in limited patient benefits. Recent single-cell RNA sequencing studies have elucidated that MM patients display distinctive transcriptional features of tumor cells, immune cells and interstitial cells, including loss of antigen presentation function of tumor cells, exhaustion of CD8+T and extracellular matrix secreted by fibroblasts to prevents immune infiltration, which leads to a poor response to immune checkpoint inhibitors (ICIs). However, cell subgroups beneficial to anti-tumor immunity and the model developed by them remain to be further identified. Methods: In this clinical study of neoadjuvant therapy with anti-PD-1 in advanced melanoma, tumor tissues were collected before and after treatment for single-nucleus sequencing, and the results were verified using multicolor immunofluorescence staining and public datasets. Results: This study describes four cell subgroups which are closely associated with the effectiveness of anti-PD-1 treatment. It also describes a cell-cell communication network, in which the interaction of the four cell subgroups contributes to anti-tumor immunity. Furthermore, we discuss a newly developed predictive model based on these four subgroups that holds significant potential for assessing the efficacy of anti-PD-1 treatment. Conclusions: These findings elucidate the primary mechanism of anti-PD-1 resistance and offer guidance for clinical drug administration for melanoma.

Circular RNA circFCHO2(hsa_circ_0002490) promotes the proliferation of melanoma by directly binding to DND1.

Circular RNAs (circRNAs) have been documented to play crucial roles in the biology of various cancers. However, their investigation in melanoma is still at an early stage, particularly as a broader mechanism beyond acting as miRNA sponges needs to be explored. We report here that circFCHO2(hsa_circ_0002490), a circRNA encompassing exons 19 and 20 of the FCHO2 gene, exhibited a consistent overexpression in melanoma tissues. Furthermore, elevated circFCHO2 levels demonstrated a positive correlation with the malignant phenotype and poor prognosis among the 158 melanoma patients studied. Besides, we observed that heightened levels of circFCHO2 promoted melanoma cell proliferation, migration, and invasion in vitro, along with contributing to tumor growth in vivo. Furthermore, we found differences in the secondary structure of circFCHO2 compared to most other circular RNA structures. It has fewer miRNA binding sites, while it has more RNA binding protein binding sites. We therefore speculate that circFCHO2 may have a function of interacting with RNA binding proteins. Mechanistically, it was confirmed by fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), and western blotting assays that circFCHO2 interacts with dead end protein homolog 1 (DND1) and reverses the inhibition of the PI3K/AKT signaling pathway by binding to DND1. Our findings reveal that circFCHO2 drives melanoma progression by regulating the PI3K/AKT signaling pathway through direct binding to DND1 and may serve as a potential diagnostic biomarker and therapeutic target for the treatment of melanoma.

Melanoma Derived Exosomes Amplify Radiotherapy Induced Abscopal Effect via IRF7/I-IFN Axis in Macrophages.

Radiotherapy (RT) can induce tumor regression outside the irradiation field, known as the abscopal effect. However, the detailed underlying mechanisms remain largely unknown. A tumor-bearing mouse model is successfully constructed by inducing both subcutaneous tumors and lung metastases. Single-cell RNA sequencing, immunofluorescence, and flow cytometry are performed to explore the regulation of tumor microenvironment (TME) by RT. A series of in vitro assays, including luciferase reporter, RNA Pulldown, and fluorescent in situ hybridization (FISH) assays, are performed to evaluate the detailed mechanism of the abscopal effect. In addition, in vivo assays are performed to investigate combination therapy strategies for enhancing the abscopal effect. The results showed that RT significantly inhibited localized tumor and lung metastasis progression and improved the TME. Mechanistically, RT promoted the release of tumor-derived exosomes carrying circPIK3R3, which is taken up by macrophages. circPIK3R3 promoted Type I interferon (I-IFN) secretion and M1 polarization via the miR-872-3p/IRF7 axis. Secreted I-IFN activated the JAK/STAT signaling pathway in CD8+ T cells, and promoted IFN-γ and GZMB secretion. Together, the study shows that tumor-derived exosomes promote I-IFN secretion via the circPIK3R3/miR-872-3p/IRF7 axis in macrophages and enhance the anti-tumor immune response of CD8+ T cells.

Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses.

Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination. Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis. Notably, we identify a strong association between MYC+ Melanoma (MYC+MEL) and FGFBP2+NKT cells with LN metastasis. Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC+MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.

Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges.

Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs. In this review, we first introduce TCR structure-based antigen recognition and signaling, then describe recent advances in neoantigens and their specific TCR screening technologies, and finally summarize ongoing clinical trials of TCR-T therapies against neoantigens. More importantly, we also present the current challenges of TCR-T cell-based immunotherapies, e.g., the safety of viral vectors, the mismatch of T cell receptor, the impediment of suppressive tumor microenvironment. Finally, we highlight new insights and directions for personalized TCR-T therapy.

Impact of Daily Step Count on Diabetes Management and Complications Among Elderly Individuals - Jiangsu Province, China, 2020-2022.

What is already known about this topic?: Current literature underscores the significance of appropriate physical activity in managing diabetes, primarily utilizing self-reported data. Yet, the impact of objectively measured physical activity in older diabetic populations remains unclear. What is added by this report?: Our research on elderly diabetic patients indicated a correlation between an increased number of daily steps and improved metabolic profiles, as well as a decrease in the incidence of cardiovascular complications. What are the implications for public health practice?: Elevated daily step counts may confer significant benefits to elderly individuals with diabetes. The use of devices to monitor these steps could serve as a potent cardiovascular marker, and hold great potential as a screening or intervention tool in community-oriented settings.

Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score.

Metastasis is a formidable challenge in the prognosis of melanoma. Accurately predicting the metastatic potential of non-metastatic melanoma (NMM) and determining effective postoperative adjuvant treatments for inhibiting metastasis remain uncertain. In this study, we conducted comprehensive analyses of melanoma metastases using bulk and single-cell RNA sequencing data, enabling the construction of a metastasis score (MET score) through diverse machine-learning algorithms. The reliability and robustness of the MET score were validated using various in vitro assays and in vivo models. Our findings revealed a distinct molecular landscape in metastatic melanoma characterized by the enrichment of metastasis-related pathways, intricate cell-cell communication, and heightened infiltration of pro-angiogenic tumor-associated macrophages compared to NMM. Importantly, patients in the high MET score group exhibited poorer prognoses and an immunosuppressive microenvironment, featuring increased infiltration of regulatory T cells and decreased infiltration of CD8+ T cells, compared to the low MET score patient group. Expression of PD-1 was markedly higher in patients with low MET scores. Anti-PD-1 (aPD-1) therapy profoundly affected antitumor immunity activation and metastasis inhibition in these patients. In summary, our study demonstrates the effectiveness of the MET score in predicting melanoma metastatic potential. For patients with low MET scores, aPD-1 therapy may be a potential treatment strategy to inhibit metastasis. Patients with high MET scores may benefit from combination therapies.

Bacterial lipoteichoic acid induces capsular contracture by activating innate immune response.

BACKGROUND: Capsular contracture is attributed to an exaggerated fibrosis response within the capsule and is partly associated with bacterial contamination in situ. However, the cellular mechanisms that initiate this response are unclear. METHODS: We developed a mouse model of capsular contracture by repeated injection of 10 µg/ml lipoteichoic acid (LTA). The histological changes in the capsule tissue were measured by hematoxylin-eosin, Masson, and immunohistochemical staining. The expression of cytokines was measured by quantitative reverse-transcription polymerase chain reaction. We also used pharmacological methods to verify the roles of macrophages and Toll-like receptor 2 (TLR2) signaling in this pathological process. RESULTS: We discovered that repeated LTA injection, at a low concentration, could induce the thickening of the capsule tissue. Macrophage infiltration and TLR2/nuclear factor-kappa B (NF-κB) signaling activated in this process could be suppressed by macrophage depletion or TLR2 receptor inhibition. CONCLUSIONS: As TLR2 signal activation was found to cause capsular contracture by inducing macrophage infiltration as a consequence of trace amounts of LTA contamination in situ, this target is helpful for understanding that chronic or repeated subclinical infection could activate capsular contracture.

Prediction of survival and immunotherapy response by the combined classifier of G protein-coupled receptors and tumor microenvironment in melanoma.

BACKGROUND: Melanoma is the deadliest form of skin tumor, and G protein-coupled receptors (GPCRs) play crucial roles in its carcinogenesis. Furthermore, the tumor microenvironment (TME) affects the overall survival (OS) and the response to immunotherapy. The combination of GPCRs and TME from a multi-omics perspective may help to predict the survival of the melanoma patients and their response to immunotherapy. METHODS: Bulk-seq, single-cell RNA sequencing (scRNA-seq), gene mutations, immunotherapy responses, and clinicopathologic feature data were downloaded from public databases, and prognostic GPCRs and immune cells were screened using multiple machine learning algorithms. The expression levels of GPCRs were detected using real-time quantitative polymerase chain reaction (qPCR) in A375 and HaCaT cell lines. The GPCR-TME classifier was constructed and verified using different cohorts and multi-omics. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and tracking tumor immunophenotype (TIP) were used to identify the key biological pathways among the GPCR-TME subgroups. Then, tumor mutational burden (TMB), vital mutant genes, antigen presentation genes, and immune checkpoints were compared among the subgroups. Finally, the differences in immunotherapy response rates among the GPCR-TME subgroups were investigated. RESULTS: A total of 12 GPCRs and five immune cell types were screened to establish the GPCR-TME classifier. No significant differences in the expression levels of the 12 GPCRs were found in the two cell lines. Patients with high GPCR score or low TME score had a poor OS; thus, the GPCRlow/TMEhigh subgroup had the most favorable OS. The scRNA-seq result revealed that immune cells had a higher GPCR score than tumor and stromal cells. The GPCR-TME classifier acted as an independent prognostic factor for melanoma. GSEA, WGCNA, and TIP demonstrated that the GPCRlow/TMEhigh subgroup was related to the activation and recruitment of anti-tumor immune cells and the positive regulation of the immune response. From a genomic perspective, the GPCRlow/TMEhigh subgroup had higher TMB, and different mutant genes. Ultimately, higher expression levels of antigen presentation genes and immune checkpoints were observed in the GPCRlow/TMEhigh subgroup, and the melanoma immunotherapy cohorts confirmed that the response rate was highest in the GPCRlow/TMEhigh cohort. CONCLUSIONS: We have developed a GPCR-TME classifier that could predict the OS and immunotherapy response of patients with melanoma highly effectively based on multi-omics analysis.

One-stop [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 total-body PET/CT examination with dual-low activity: a feasibility study.

PURPOSE: Positron emission tomography/computed tomography (PET/CT) based on fibroblast activation protein inhibitors (FAPI) has shown complementary values to 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in cancer imaging. This study aimed to investigate the feasibility of a one-stop FDG-FAPI dual-tracer imaging protocol with dual-low activity for oncological imaging. METHODS: Nineteen patients with malignancies underwent one-stop [18F]FDG (0.37 MBq/kg) PET (PETFDG) and dual-tracer PET 30-40 and 50-60 min (hereafter, PETD30-40 and PETD50-60, respectively) after additional injection of [68Ga]Ga-DOTA-FAPI-04 (0.925 MBq/kg), with a single diagnostic CT to generate the PET/CT. The lesion detection rate and tumor-to-normal ratios (TNRs) of tracer uptake were compared between PETFDG/CT and PETD50-60/CT and between PETD50-60/CT and PETD30-40/CT. In addition, a visual scoring system was established to compare the lesion detectability. RESULTS: The dual-tracer PETD50-60 and PETD30-40/CT showed similar performance in detecting primary tumors but presented significantly higher lesion TNRs than PETFDG. Significantly, more metastases with higher TNRs were identified on PETD50-60 than PETFDG (491 vs. 261, P < 0.001). The dual-tracer PETD50-60 received significantly higher visual scores than single PETFDG (111 vs. 10) in demonstrating both primary tumors (12 vs. 2) and metastases (99 vs. 8). However, these differences were not significant between PETD50-60 and PETD30-40. These resulted in tumor upstaging in 44.4% patients taking PET/CT for initial assessment, and more recurrences (68 vs. 7) were identified in patients taking PET/CT for restaging, both on PETD50-60 and PETD30-40, compared to PETFDG. The reduced effective dosimetry per patient (26.2 ± 2.57 mSv) was equal to that of a single standard whole-body PET/CT. CONCLUSION: The one-stop dual-tracer dual-low-activity PET imaging protocol combines the strengths of [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 with shorter duration and lesser radiation and is thus clinically applicable.

Genomic Data Mining Reveals Abundant Uncharacterized Transporters in Coccidioides immitis and Coccidioides posadasii.

Coccidioides immitis and Coccidioides posadasii are causative agents of coccidioidomycosis, commonly known as Valley Fever. The increasing Valley Fever cases in the past decades, the expansion of endemic regions, and the rising azole drug-resistant strains have underscored an urgent need for a better understanding of Coccidioides biology and new antifungal strategies. Transporters play essential roles in pathogen survival, growth, infection, and adaptation, and are considered as potential drug targets. However, the composition and roles of transport machinery in Coccidioides remain largely unknown. In this study, genomic data mining revealed an abundant, uncharacterized repertoire of transporters in Coccidioides genomes. The catalog included 1288 and 1235 transporter homologs in C. immitis and C. posadasii, respectively. They were further annotated to class, subclass, family, subfamily and range of substrates based on the Transport Classification (TC) system. They may play diverse roles in nutrient uptake, metabolite secretion, ion homeostasis, drug efflux, or signaling. This study represents an initial effort for a systems-level characterization of the transport machinery in these understudied fungal pathogens.

Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review.

Background: Major depressive disorder (MDD) and treatment-resistant depression (TRD) represent a global source of societal and health burden. To advise proper management of inflammation-related depression among TRD patients, it is important to identify therapeutic clinical treatments. A key factor is related to proinflammatory cytokines such as interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor- (TNF-) α which have been implicated in the pathogenesis of depressive symptoms in MDD patients. Ketamine may provide an anti-inflammatory therapeutic strategy by targeting proinflammatory pathways associated with depressive disorders, which may be exacerbated in the ageing population with TRD. Objective: Despite a burgeoning body of literature demonstrating that inflammation is linked to TRD, there is still a lack of comprehensive research on the relationship between proinflammatory biomarkers and ketamine's antidepressant effect on TRD patients. Method: The Cochrane Library and PubMed/MEDLINE databases were systematically searched from inception up to February 1, 2022, adopting broad inclusion criteria to assess clinical topics related to the impact of ketamine on inflammatory cytokines in TRD patients. The present work is in compliance with the World Health Organization Rapid Review Guide. Results: Five out of the seven studies examined in this review show that ketamine infusion may reduce depressive symptoms with a quick start of effect on TRD patients. Based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D) scores, the overall response rate for ketamine was 56%; that is, 56% of those treated with ketamine had MADRS/HAM-D scores decreased by at least 50%. Conclusions: While the anti-inflammatory effects of ketamine modulate specific proinflammatory cytokines, its rapid antidepressant effect on TRD patients remains inconsistent. However, our study findings can provide a reliable basis for future research on how to improve systemic inflammatory immune disorders and mental health. We suggest that ketamine infusion may be part of a comprehensive treatment approach in TRD patients with elevated levels of depression-specific inflammatory biomarkers.

Intratumoral CD73: An immune checkpoint shaping an inhibitory tumor microenvironment and implicating poor prognosis in Chinese melanoma cohorts.

Background: As a novel immune checkpoint, CD73 has been reported to play prominent roles in several malignancies. However, the significance of CD73 in melanoma remains ambiguous. This study sought to reveal the impact of CD73 on the tumor microenvironment (TME) and patients' prognosis, and to investigate whether CD73 could be a therapeutic target in Chinese melanomas, which were dominated by acral and mucosal subtypes. Methods: Two independent Chinese cohorts of 194 patients with melanoma were enrolled. CD73 and PD-L1 expression as well as CD8+ and CD56+ cell infiltrations were evaluated by immunohistochemistry in 194 resected melanoma samples. Clinical outcomes of patients were assessed utilizing the Kaplan-Meier plotter and Cox proportional hazard analysis. RNA-seq data was obtained from TCGA database. Gene set functional annotations were performed based on GO, KEGG and GSEA analysis. CIBERSORT, ssGSEA and TIMER were used to explore the association between CD73 and immune infiltration. These findings were validated by establishing tumor xenograft model, and functions of tumor-infiltrating immune cells were examined by flow cytometry and immunofluorescence. Results: High CD73 expression showed poorer clinical outcomes and was identified as an independent prognostic indicator for survival in two cohorts. Expression of CD73 was more prevalent than PD-L1 in Chinese melanoma cohorts (54.6% vs 23.2%). Co-expression of both immune checkpoints was infrequent (12.9%) in melanoma, and 54.4% of PD-L1 negative cases showed elevated expression of CD73. CD73high tumors showed a microenvironment with fewer CD8+ T cells and CD56+ NK cells infiltration, which displayed a dysfunctional phenotype. With the treatment of CD73 inhibitor APCP, the amount of CD8+ T cells and CD56+ NK cells infiltrated in tumors was elevated and the immunosuppressive effect of CD73 was eliminated. Conclusions: High CD73 expression was associated with an inhibitory TME and adverse clinical outcomes of melanoma. In comparison to PD-L1, CD73 was more prevalent and possessed more definite prognostic significance. Therefore, it may serve as a prognostic indicator and immunotherapeutic target next to PD-L1 in melanoma for Chinese population.

Ultrafast 30-s total-body PET/CT scan: a preliminary study.

PURPOSE: The aim of this study is to explore the diagnostic value of the images obtained in ultrafast 30-s acquisition time by the total-body PET/CT (18F-FDG injection dose of about 3.7 MBq/kg), and to evaluate whether they can meet the requirements of clinical diagnosis or not. METHODS: This retrospective study explored the clinical value of ultrafast 30-s 18F-FDG total-body PET/CT in 88 oncology patients, using the post-surgical pathological diagnosis as the reference standard. The data were acquired over 300 s and reconstructed using all 300-s data (G300) and only the initial 30 s (G30). Two readers independently assessed all images qualitatively and quantitatively. The diagnostic performance was compared between G300 and G30. RESULTS: The G300 average qualitative score was higher than G30 (P < 0.001). G300 and G30 also differed quantitatively in the liver and mediastinum SUVmax, SD, and SNR (all P < 0.001), but had similar sensitivities (89.09% vs. 86.36%, P = 0.250). The G300 group had higher accuracy (79.73%) and a larger area under the curve (0.709) than G30 (77.70% and 0.695, respectively; all P > 0.05). CONCLUSION: The 30-s total-body PET/CT could meet clinical diagnostic requirements for malignant tumors in patients intolerant to prolonged horizontal positioning.

Genome-wide screening and immune landscape suggest a potential-m6A-related lncRNA risk signature for predicting prognosis of melanoma.

Background: Melanoma is the most dangerous form of skin cancer because of its high metastatic potential. Potential-N6-methyladenosine (m6A)-related long noncoding RNAs (pMRlncRNAs) play a vital role in malignancy. The identification of prognostic-related pMRlncRNAs and development of risk signatures could improve the prognosis and promote the precise treatment of melanoma. Methods: Gene expression and relevant clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognostic-related pMRlncRNAs were selected using univariate Cox regression analysis. Patients with melanoma were classified into different subtypes using the "ConsensusClusterPlus" package, and the ESTIMATE algorithm was applied to depict their immune landscape. A pMRlncRNA risk signature was developed using least absolute shrinkage and selection operator regression analysis and verified using survival analysis and receiver operating characteristic curves. Gene set enrichment analysis (GSEA) was used to investigate the underlying biological pathways. The relationships between risk score and clinicopathological characteristics, as well as programmed cell death-ligand 1 (PD-L1) expression level, were investigated. A nomogram with calibration curves was established to comprehensively predict the outcome of melanoma. Results: Fifteen pMRlncRNAs were significantly associated with overall survival (OS). Two cluster subtypes were identified by consensus clustering. Patients in cluster 2 were associated with better OS, higher PD-L1 expression level, lower T stage, and higher ESTIMATEScore, ImmuneScore, and StromalScore than those in cluster 1. There were differences in immune cell infiltration between the 2 clusters. Ten pMRlncRNAs with prognostic value were selected to develop a risk signature, that functioned as an independent prognostic factor for melanoma. Patients with low-risk scores had a better prognosis in general. The area under the curve (AUC) value (0.720), as well as 1-, 3-, and 5-year calibration curves, revealed that the risk signature has suitable predictive power for prognosis. GSEA revealed 10 pathways that might play important roles in melanoma. Moreover, patients with high-risk scores were associated with advanced T stage, cluster 1, lower ImmuneScore, and higher PD-L1 expression level. Conclusions: We developed a novel 10-pMRlncRNA risk signature that could elucidate the crucial role of pMRlncRNAs in the immune landscape of melanoma and predict prognosis.

Diagnostic performance of total-body 18F-FDG PET/CT with fast 2-min acquisition for liver tumours: comparison with conventional PET/CT.

PURPOSE: To comparatively evaluate the diagnostic performances of total-body 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) with fast 2-min acquisition and conventional PET/CT in liver cancer patients. METHODS: This study included 156 patients with liver tumours. Seventy-eight patients underwent total-body PET/CT. PET raw data were reconstructed using acquisition durations of 2 min (G2) and 15 min (G15). Another 78 patients with liver lesions (control patients) underwent conventional uMI780 PET/CT (G780). All patients were evaluated based on TNM staging. The maximum tumour standardized uptake value (tumour SUVmax), mean normal liver SUV (SUVmean), and tumour SUVmax-to-liver SUVmean ratio (TLR) were determined for all patients. G15 data were used as the reference in the lesion detectability analysis. The diagnostic performances of PET/CT in terms of visual parameters and of PET in terms of semi-quantitative parameters such as SUVmax and TLR were evaluated. Receiver operating characteristics (ROC) curve analysis of SUVmax and TLR at G2 was performed. Pathologic findings of surgical specimens served as the gold standard for all patients. RESULTS: The lesions found in G15 were also noted in G2; three lymph nodes were missed in G2. However, no significant difference was found in the TNM stage among G2, G15, and G780. For benign and malignant lesions, the liver SUVmean in G2 and G15 was higher than that in G780 (all P < 0.05). The tumour SUVmax and TLR in G2 were equivalent to those in G15 and G780 regardless of whether the lesions were benign or malignant. ROC curve analysis (SUVmax cutoff: 4.34, TLR cutoff: 1.34) demonstrated that G2 also had good sensitivity in detecting liver cancer. CONCLUSION: The diagnostic performance of total-body PET/CT in G2 was comparable to that in G15 among liver cancer patients. Further, the diagnostic efficiency of total-body PET/CT imaging with fast 2-min acquisition and conventional PET/CT was similar.