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1.
Yanhong Wu;Hongying He;Kairong Zheng;Zhenxin Qin;Naikun Cai;Shuguang Zuo;Xiao Zhu; 《Pigment cell & melanoma research》2024,37(4):496-509
Recent years have seen rising mortality rates linked to cutaneous melanoma (SKCM), despite advances in immunotherapy. Understanding RNA N6-methyladenosine (M6A) significance in SKCM is crucial for prognosis, tumor microenvironment (TME), immune cell presence, and immunotherapy efficacy. We analyzed 23 M6A regulators using SKCM samples from TCGA and GEO databases, identifying three M6A modification patterns linked to TME cell infiltration. Principal component analysis (PCA) yielded an M6A score for individual tumors, utilizing patient gene expression profiles and CNV data from TCGA. M6A modification patterns play a crucial role in SKCM development and progression, influencing tumor attributes such as inflammatory stage, subtype, TME interstitial activity, and genetic mutations. The M6A score independently predicts patient outcomes and correlates with improved response to immunotherapy, validated across anti-PD-1 and anti-PD-L1 therapy cohorts. M6A modifications significantly impact the TME landscape, with the M6A score serving as a predictive marker for immunotherapy response. Integrating M6A-related information into clinical practice could revolutionize SKCM management and treatment strategies. 相似文献
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Shiyi Liu Saijiao Li Yanqing Wang Feiyan Wang Li Zhang Shu Xian Dongyong Yang Mengqin Yuan Fangfang Dai Xin Zhao Yuping Liu Yumeng Jin Zihang Zeng Omer Kamal Ahmed Mahgoub Chenliang Zhou Yanxiang Cheng 《Journal of cellular biochemistry》2020,121(3):2571-2581
In this study, we attempted to evaluate the prognostic value of infiltrating immune/stromal cells in clear cell renal cell carcinoma (ccRCC), by using the immune scores and stromal scores based on the “Estimation of STromal and Immune cells in MAlignant Tumours using Expression data” algorithm to represent the levels of infiltrating immune cells and stromal cells. We found that the infiltrating immune cells were associated with poor prognosis of ccRCC. To assess the role of infiltrating immune cells in ccRCC cells, first, we performed differentially expressed genes analysis and functional analysis for validation. The results showed that the underlying mechanism by which infiltrating immune cells promoted cancer progression involved in regulating the nuclear division, angiogenesis, and immune response. Next, we investigated the relationship between infiltrating immune cells and mutations in ccRCC cells. We found that the infiltrating immune cells have certain effects on genetic mutations. In conclusion, infiltrating immune cells within the tumor microenvironment can be used to predict prognosis in ccRCC. 相似文献
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Zhao Zhang Zeyan Li Zhao Liu Xiang Zhang Nengwang Yu Zhonghua Xu 《Journal of cellular biochemistry》2020,121(7):3606-3615
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor. Previous studies have shown that the interaction between tumor cells and microenvironment has an important impact on prognosis. Immune and stromal cells are two vital components of the tumor microenvironment. Our study aimed to better understand and explore the genes involved in immune/stromal cells on prognosis. We used the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm to calculate immune/stromal scores. According to the scores, we divided ccRCC patients from The Cancer Genome Atlas database into low and high groups and identified the genes which were differentially expressed and significantly associated with prognosis. The result of functional enrichment analysis and protein-protein interaction networks indicated that these genes mainly were involved in extracellular matrix and regulation of cellular activities. Then another independent cohort from the International Cancer Genome Consortium database was used to validate these genes. Finally, we acquired a list of microenvironment-related genes that can predict prognosis for ccRCC patients. 相似文献
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Xiangyang Deng Dongdong Lin Xiaojia Zhang Xuchao Shen Zelin Yang Liang Yang Xiangqi Lu Lisheng Yu Nu Zhang Jian Lin 《Journal of cellular physiology》2020,235(10):7321-7331
The tumor microenvironment is highly correlated with tumor occurrence, progress, and prognosis. We aimed to investigate the immune-related gene (IRG) expression and immune infiltration pattern in the tumor microenvironment of lower-grade glioma (LGG). We employed the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm to calculate immune and stromal scores and identify prognostic IRG based on The Cancer Genome Atlas data set. The potential molecular functions of these genes were explored with the help of functional enrichment analysis and the protein–protein interaction network. Remarkably, three cohorts that were downloaded from the Chinese Glioma Genome Atlas database were analyzed to further verify the prognostic values of these genes. Moreover, the Tumor IMmune Estimation Resource (TIMER) algorithm was used to estimate the abundance of infiltrating immune cells and explore the immune infiltration pattern in LGG. And unsupervised cluster analysis determined three clusters of the immune infiltration pattern and indicated that CD8+ T cells and macrophages were significantly associated with LGG outcomes. Altogether, our study identified a list of prognostic IRGs and provided a perspective to explore the immune infiltration pattern in LGG. 相似文献
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van Kempen LC Ruiter DJ van Muijen GN Coussens LM 《European journal of cell biology》2003,82(11):539-548
Evolution of neoplastic cells has generally been regarded as a cumulative intrinsic process resulting in altered cell characteristics enabling enhanced growth properties, evasion of apoptotic signals, unlimited replicative potential and gain of properties enabling the ability to thrive in ectopic tissues and in some cases, ability to metastasize. Recently however, the role of the neoplastic microenvironment has become appreciated largely due to the realization that tumors are not merely masses of neoplastic cells, but instead, are complex tissues composed of both a non-cellular (matrix proteins) and a cellular 'diploid' component (tumor-associated fibroblasts, capillary-associated cells and inflammatory cells), in addition to the ever-evolving neoplastic cells. With these realizations, it has become evident that early and persistent inflammatory responses observed in or around many solid tumors, play important roles in establishing an environment suitable for neoplastic progression by providing diverse factors that alter tissue homeostasis. Using cutaneous melanoma and squamous cell carcinoma as tumor models, we review the current literature focussing on inflammatory and tumor-associated fibroblast responses as critical mediators of neoplastic progression for these malignancies. 相似文献
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Xiang-Yong Hao An-Qiang Li Hao Shi Tian-Kang Guo Yan-Fei Shen Yuan Deng Li-Tian Wang Tao Wang Hui Cai 《Bioscience reports》2021,41(3)
Purpose: To build a novel predictive model for hepatocellular carcinoma (HCC) patients based on DNA methylation data.Methods: Four independent DNA methylation datasets for HCC were used to screen for common differentially methylated genes (CDMGs). Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the biological roles of CDMGs in HCC. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were performed to identify survival-related CDMGs (SR-CDMGs) and to build a predictive model. The importance of this model was assessed using Cox regression analysis, propensity score-matched (PSM) analysis and stratification analysis. A validation group from the Cancer Genome Atlas (TCGA) was constructed to further validate the model.Results: Four SR-CDMGs were identified and used to build the predictive model. The risk score of this model was calculated as follows: risk score = (0.01489826 × methylation level of WDR69) + (0.15868618 × methylation level of HOXB4) + (0.16674959 × methylation level of CDKL2) + (0.16689301 × methylation level of HOXA10). Kaplan–Meier analysis demonstrated that patients in the low-risk group had a significantly longer overall survival (OS; log-rank P-value =0.00071). The Cox model multivariate analysis and PSM analysis identified the risk score as an independent prognostic factor (P<0.05). Stratified analysis results further confirmed this model performed well. By analyzing the validation group, the results of receiver operating characteristic (ROC) curve analysis and survival analysis further validated this model.Conclusion: Our DNA methylation-based prognosis predictive model is effective and reliable in predicting prognosis for patients with HCC. 相似文献
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Hong Weng Shuai Yuan Qiao Huang Xian-Tao Zeng Xing-Huan Wang 《Journal of cellular and molecular medicine》2021,25(7):3258-3271
The immunophenotype of bladder cancer plays a pivotal role in the prognosis of cancer, but the effect of different epigenetic factors on different immunophenotypes in bladder tumours remains unclear. This study used multi-omics data analysis to provide molecular basis support for different immune phenotypes. Unsupervised cluster analysis revealed distinct subclusters with higher (subcluster B2) or lower cytotoxic immune phenotypes (subcluster A1) related to PD-L1 and IFNG expression. Mutational landscape analyses showed that the mutation level of TP53 in subcluster B1 was highest than other subclusters, and subcluster B1 had a lower frequency of concurrent mutation than subcluster A2. A total of 2364 differentially expressed genes were identified between subclusters A2 and B1, and the main functions of the up-regulated genes in subcluster B1 were enriched in the activation of T cells and other related pathways. We found that STAT1 was a key gene in a gene regulatory network related to immune phenotypes in bladder cancer. Finally, we constructed a prognostic prediction model by LASSO Cox regression which could distinguish high-risk and low-risk cases significantly. In conclusion, the present study addressed a field synopsis between genetic and epigenetic events in immune phenotypes of bladder cancer. 相似文献
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Satoshi Serada Atsushi Tanemura Fei Yang Shintaro Nomura Akira Kudo Kenji Izuhara Hiroyuki Murota Minoru Fujimoto Ichiro Katayama Tetsuji Naka 《Pigment cell & melanoma research》2014,27(4):630-639
Given no reliable therapy for advanced malignant melanoma, it is important to elucidate the molecular mechanisms underlying the disease progression. Using a quantitative proteomics approach, the ‘isobaric tags for relative and absolute quantitation (iTRAQ)’ method, we identified that the extracellular matrix protein, periostin (POSTN), was highly expressed in invasive melanoma compared with normal skin. An immunohistochemical analysis showed that POSTN was expressed in all invasive melanoma (n = 20) and metastatic lymph node (n = 5) tissue samples, notably restricted in their stroma. In terms of the intercellular regulation of POSTN, we found that there was upregulation of POSTN when melanoma cells and normal human dermal fibroblasts (NHDFs) were cocultured, with restricted expression of TGF‐β1 and TGF‐β3. In a functional analyses, recombinant and NHDF‐derived POSTN significantly accelerated melanoma cell proliferation via the integrin/mitogen‐activated protein kinase (MAPK) signaling pathway in vitro. The size of implanted melanoma tumors was significantly suppressed in POSTN/Rag2 double knockout mice compared with Rag2 knock‐out mice. These results indicate that NHDF‐derived POSTN accelerates melanoma progression and might be a promising therapeutic target for malignant melanoma. 相似文献
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Axel P. Stevens Barbara Spangler Susanne Wallner Marina Kreutz Katja Dettmer Peter J. Oefner Anja K. Bosserhoff 《Journal of cellular biochemistry》2009,106(2):210-219
Recent studies have shown that a loss of methylthioadenosine phosphorylase (MTAP) gene expression exerts a tumor‐promoting effect, including induction of invasiveness, enhanced cell proliferation, and resistance against cytokines. To date, the molecular mechanisms underlying these effects remain unknown. Since the loss of MTAP expression resulted in induced secretion of 5′‐deoxy‐5′‐(methylthio)adenosine (MTA), we hypothesized that MTA might modulate the observed effects. We first determined MTA levels produced by tumor cells in vitro and in situ by means of stable isotope dilution liquid chromatography tandem mass spectrometry. Subsequently, we revealed induction of matrix metalloproteinase (MMP) and growth factor gene expression in melanoma cells accompanied by enhanced invasion and vasculogenic mimicry. In addition, MTA induced the secretion of basis fibroblast growth factor (bFGF) and MMP3 from fibroblasts and the upregulation of activator protein‐1 (AP‐1) activity in melanoma cells and fibroblasts. In summary, we demonstrated a tumor‐supporting role of MTA. J. Cell. Biochem. 106: 210–219, 2009. © 2008 Wiley‐Liss, Inc. 相似文献
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BackgroundSpindle and Kinetochore Associated Complex Subunit 3 (SKA3) is a part of the SKA complex, which plays a key role in cell mitosis. Studies have shown that SKA3 was associated with cancer progression. However, its role in skin cutaneous melanoma (SKCM) remains unclear. Here, we investigated the expression level and prognostic value of SKA3 in SKCM.MethodsBased on public databases, univariate and multivariate Cox regression analyses were used to investigate the different expression of SKA3 between SKCM and normal tissues. Then, the relationship between SKA3 expression level and prognosis was assessed. PPI network and functional enrichment analysis were performed. ESTIMATE and CIBERSORT were expected to evaluate the SKA3 expression and immune status. CCK8, wound healing, transwell assays and tumor xenograft trial were performed to detect the SKA3 function in cell viability, migration and invasion of the cell lines.ResultsThe SKA3 was highly expressed in SKCM tissues. SKA3 overexpression was associated with poor survival and immune status. SKA3 knockdown inhibited cell viability, migration and invasion of SKCM cells.ConclusionSKA3 is involved in the progression of SKCM and may serve as a new prognostic biomarker and therapeutic target. 相似文献
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Xian rui Wu Zheng Chen Yang Liu Zi zi Chen Fengjie Tang Zhi zhao Chen Jing jing Li Jun lin Liao Ke Cao Xiang Chen Jianda Zhou 《Journal of cellular and molecular medicine》2021,25(17):8405-8418
Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N1-methyladenosine (m1A), 5-methylcytosine (m5C), N6-methyladenosine (m6A)-related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m1A-, m5C- and m6A-related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator-related prognostic signature. The nine-gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high-risk group was correlated with T-cell suppression, while the low-risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m1A-, m5C- and m6A-related regulators may also be promising biomarkers for future research. 相似文献
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Luiza Martins Nascentes Melo Suresh Kumar Valeria Riess Krystina J. Szylo Robin Eisenburger Dirk Schadendorf Jessalyn M. Ubellacker Alpaslan Tasdogan 《Pigment cell & melanoma research》2023,36(2):206-223
Metastatic melanoma is a complex and deadly disease. Due to its complexity, the development of novel therapeutic strategies to inhibit metastatic melanoma remains an outstanding challenge. Our ability to study metastasis is advanced with the development of in vitro and in vivo models that better mimic the different steps of the metastatic cascade beginning from primary tumor initiation to final metastatic seeding. In this review, we provide a comprehensive summary of in vitro models, in vivo models, and in silico platforms to study the individual steps of melanoma metastasis. Furthermore, we highlight the advantages and limitations of each model and discuss the challenges of how to improve current models to enhance translation for melanoma cancer patients and future therapies. 相似文献
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Grant M. Fischer Y. N. Vashisht Gopal Jennifer L. McQuade Weiyi Peng Ralph J. DeBerardinis Michael A. Davies 《Pigment cell & melanoma research》2018,31(1):11-30
Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There are also data to support that the metabolic phenotypes of melanoma cells depend upon contributions from both intrinsic oncogenic pathways and extrinsic factors in the tumor microenvironment. This review summarizes current understanding of the metabolic processes that promote cutaneous melanoma tumorigenesis and progression, the regulation of cancer cell metabolism by the tumor microenvironment, and the impact of metabolic pathways on targeted and immune therapies. 相似文献
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Kristýna Nmejcov Ivana Tich Michaela Brt Ondej Kodet Miroslav Dra Radek Jaka Romana Michlkov Pavel Dundr 《Pigment cell & melanoma research》2019,32(3):412-423
The objective of our study was to compare the five different scoring methods of tumor‐infiltrating lymphocytes (TILs) assessment in a group of 213 cases of superficial spreading and nodular melanoma. The scoring methods include (a) Clark scoring; (b) Melanoma Institute Australia system; (c) scoring system used in the study of Saldanha et al.; (d) scoring system used in the TCGA study and modified by Park et al.; and (e) the system recently proposed by the “International Immuno‐Oncology Biomarker Working Group” for TILs scoring in all solid tumors. Prediction of survival with three main outcomes—disease‐specific‐free survival, local recurrence‐free survival, and distant metastasis‐free survival—was evaluated. The prognostic value of TILs showed statistical significance in univariate analysis regarding all three of the outcomes only for three of the five evaluated methods; the Clark scoring, the Melanoma Institute Australia system, and the system proposed by the “International Immuno‐Oncology Biomarker Working Group”. However, in multivariate analysis with covariants including Breslow thickness, type of melanoma, location, sex, and age, we did not find TILs to be an independent prognostic factor. 相似文献
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Wang T Ge Y Xiao M Lopez-Coral A Azuma R Somasundaram R Zhang G Wei Z Xu X Rauscher FJ Herlyn M Kaufman RE 《Pigment cell & melanoma research》2012,25(4):493-505
The presence of tumor-associated macrophages (TAMs) in melanomas is correlated with a poor clinical prognosis. However, there is limited information on the characteristics and biological activities of human TAMs in melanomas. In this study, we developed an in vitro method to differentiate human monocytes to macrophages using modified melanoma-conditioned medium (MCM). We demonstrate that factors from MCM-induced macrophages (MCMI-Mφ) express both M1-Mφ and M2-Mφ markers and inhibit melanoma-specific T-cell proliferation. Furthermore, microarray analyses reveal that the majority of genes up-regulated in MCMI-Mφ are associated with tumor invasion. The most strikingly up-regulated genes are CCL2 and MMP-9. Consistent with this, blockade of both CCL-2 and MMPs diminish MCMI-Mφ-induced melanoma invasion. Finally, we demonstrated that both MCMI-Mφ and in vivo TAMs express the pro-invasive, melanoma-associated gene, glycoprotein non-metastatic melanoma protein B. Our study provides a framework for understanding the mechanisms of cross-talk between TAMs and melanoma cells within the tumor microenvironment. 相似文献
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Rong-Hua Yang Bo Liang Jie-Hua Li Xiao-Bing Pi Kai Yu Shi-Jian Xiang Ning Gu Xiao-Dong Chen Si-Tong Zhou 《Journal of cellular and molecular medicine》2021,25(23):10990-11001
Skin cutaneous melanoma (SKCM) is one of the most destructive skin malignancies and has attracted worldwide attention. However, there is a lack of prognostic biomarkers, especially tumour microenvironment (TME)-based prognostic biomarkers. Therefore, there is an urgent need to investigate the TME in SKCM, as well as to identify efficient biomarkers for the diagnosis and treatment of SKCM patients. A comprehensive analysis was performed using SKCM samples from The Cancer Genome Atlas and normal samples from Genotype-Tissue Expression. TME scores were calculated using the ESTIMATE algorithm, and differential TME scores and differentially expressed prognostic genes were successively identified. We further identified more reliable prognostic genes via least absolute shrinkage and selection operator regression analysis and constructed a prognostic prediction model to predict overall survival. Receiver operating characteristic analysis was used to evaluate the diagnostic efficacy, and Cox regression analysis was applied to explore the relationship with clinicopathological characteristics. Finally, we identified a novel prognostic biomarker and conducted a functional enrichment analysis. After considering ESTIMATEScore and tumour purity as differential TME scores, we identified 34 differentially expressed prognostic genes. Using least absolute shrinkage and selection operator regression, we identified seven potential prognostic biomarkers (SLC13A5, RBM24, IGHV3OR16-15, PRSS35, SLC7A10, IGHV1-69D and IGHV2-26). Combined with receiver operating characteristic and regression analyses, we determined PRSS35 as a novel TME-based prognostic biomarker in SKCM, and functional analysis enriched immune-related cells, functions and signalling pathways. Our study indicated that PRSS35 could act as a potential prognostic biomarker in SKCM by investigating the TME, so as to provide new ideas and insights for the clinical diagnosis and treatment of SKCM. 相似文献