المؤلفون: Chen Ye, Sihan Jiang, Tanlun Zeng, Shaohui He, Jinjin Cao, Jianru Xiao

المصدر: Discover Oncology, Vol 15, Iss 1, Pp 1-18 (2024)

مصطلحات موضوعية: LOXL2, Pan-cancer analysis, Prognosis, Immunity, Cellular senescence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract LOXL2, an enzyme belonging to the LOX family, facilitates the cross-linking of extracellular matrix (ECM) elements. However, the roles of the LOXL2 gene in mechanisms of oncogenesis and tumor development have not been clearly defined. In this pan-cancer study, we examined the notable disparity in LOXL2 expression at the mRNA and protein levels among various cancer types and elucidated its interconnected roles in tumor progression, mutational profile, immune response, and cellular senescence. Apart from investigating the hyperexpression of LOXL2 being related to poorer prognosis in different types of tumors, this study also unveiled noteworthy connections between LOXL2 and genetic mutations, infiltration of tumor immune cells, and genes in immune checkpoint pathways. Further analysis revealed the participation of LOXL2 in multiple pathways related to cancer extracellular matrix remodeling and cellular senescence. Moreover, our investigation uncovered that the knockdown and inhibition of LOXL2 significantly attenuated the proliferation and migration of PC-9 and HCC-LM3 cells. The knock-down and inhibition of LOXL2 enhanced cellular senescence in lung and liver cancer cells, as confirmed by SA-β-Gal staining and quantitative RT-PCR analyses. This comprehensive analysis offers valuable insights on the functions of LOXL2 in different types of cancer and its role in regulating the senescence of cancer cells.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2730-6011Test

الوصول الحر: https://doaj.org/article/d5003ba33aa1485795138cdb64810c4fTest

المؤلفون: Bin Yao, Weikang Hu, Yu Chen, Jing Li, Kuirong Jiang, Jin Dou

المصدر: European Journal of Medical Research, Vol 29, Iss 1, Pp 1-18 (2024)

مصطلحات موضوعية: Tumor necrosis factor receptor-associated factors (TRAFs), Pan-cancer analysis, Tumor microenvironment (TME), Immune, Cancer prognosis, Drug sensitivity, Medicine

الوصف: Abstract Background Tumor necrosis factor receptor-associated factors family genes play a pivotal role in tumorigenesis and metastasis, functioning as adapters or E3 ubiquitin ligases across various signaling pathways. To date, limited research has explored the association between tumor necrosis factor receptor-associated factors family genes and the clinicopathological characteristics of tumors, immunity, and the tumor microenvironment (TME). This comprehensive study investigates the relationship between tumor necrosis factor receptor-associated factors family and prognosis, TME, immune response, and drug sensitivity in a pan-cancer context. Methods Utilizing current public databases, this study examines the expression levels and prognostic significance of tumor necrosis factor receptor-associated factors family genes in a pan-cancer context through bioinformatic analysis. In addition, it investigates the correlation between tumor necrosis factor receptor-associated factors expression and various factors, including the TME, immune subtypes, stemness scores, and drug sensitivity in pan-cancer. Results Elevated expression levels of tumor necrosis factor receptor-associated factor 2, 3, 4, and 7 were observed across various cancer types. Patients exhibiting high expression of these genes generally faced a worse prognosis. Furthermore, a significant correlation was noted between the expression of tumor necrosis factor receptor-associated factors family genes and multiple dimensions of the TME, immune subtypes, and drug sensitivity.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2047-783XTest

الوصول الحر: https://doaj.org/article/f9b05df82ffd45bc91e2872f2e21795aTest

المؤلفون: Wu Z, Huang C

المصدر: International Journal of General Medicine, Vol Volume 17, Pp 2575-2592 (2024)

مصطلحات موضوعية: mrc1, biomarker, immunotherapy, single-cell, pan-cancer analysis, Medicine (General), R5-920

الوصف: Zhiwei Wu, Changhao Huang Department of Organ Transplantation, XiangYa Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Changhao Huang, Email Chhuang@csu.edu.cnPurpose: Mannose receptor C-type 1 (MRC1) is an endocytic lectin receptor primarily expressed in macrophages, dendritic cells, and some endothelial cells. However, the role of MRC1 in cancers remains unclear.Methods: We analyzed MRC1 expression using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and single-cell datasets. We systematically explored the prognostic implications and diagnostic value of MRC1. Immune-related indicators, including immune cells, immune scores, and immune checkpoint molecules, were used to estimate their correlation with MRC1 expression. Finally, we explored its potential ties to immunotherapy success markers such as tumor mutation burden and DNA repair genes.Results: MRC1 showed both pro- and anti-tumor leanings depending on the cancer types. High levels correlated with poorer outcomes in six cancers but improved prognosis in some cancers like glioblastoma multiforme. This trend extended to the immune arena, where MRC1 intertwined with diverse immune parameters, suggesting its influence on affecting the tumor’s immunological landscape. Intriguingly, its expression positively associated with factors favoring immunotherapy efficacy while negatively correlating with some potential barriers. Single-cell analysis pinpointed a specific link between MRC1 and DNA damage/repair pathways in breast cancer.Conclusion: Our study provides a comprehensive landscape of MRC1 levels and diverse regulatory patterns in different cancers, deepening the understanding of MRC1’s roles in tumorigenesis and immunity.Keywords: MRC1, biomarker, immunotherapy, single-cell, pan-cancer analysis

وصف الملف: electronic resource

العلاقة: https://www.dovepress.com/unveiling-the-impact-of-mrc1-on-immune-infiltration-and-patients-progn-peer-reviewed-fulltext-article-IJGMTest; https://doaj.org/toc/1178-7074Test

الوصول الحر: https://doaj.org/article/ac9c29ea4cf44b2eb74ccf6350b664a3Test

المؤلفون: Hua Huang, Lianchun Su, Ruihao Zhang, Di Wu, Chen Ding, Chen Chen, Guangsheng Zhu, Peijun Cao, Xuanguang Li, Yongwen Li, Hongyu Liu, Jun Chen

المصدر: Discover Oncology, Vol 15, Iss 1, Pp 1-15 (2024)

مصطلحات موضوعية: Pan-cancer analysis, Bioinformatics, Nicotinamide N-methyltransferase, Tumor immune microenvironment, Immune checkpoint, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract The identification of effective therapeutic targets plays a pivotal role in advancing cancer treatment outcomes. We employed a comprehensive pan-cancer analysis, complemented by experimental validation, to explore the potential of Nicotinamide N-methyltransferase (NNMT) as a promising therapeutic strategy for human cancers. By analyzing large-scale transcriptomic datasets across various cancer types, we consistently observed upregulated expression of NNMT. Furthermore, elevated NNMT expression correlated with inferior overall survival in multiple cancer cohorts, underscoring its significance as a prognostic biomarker. Additionally, we investigated the relationship between NNMT expression and the tumor immune microenvironment, which plays a crucial role in regulating anti-tumor immune responses. To confirm the malignant functions of NNMT in tumor cells, we conducted a series of cell-based experiments, revealing that NNMT promotes cancer cell proliferation and invasion, indicative of its oncogenic properties. The integration of computational analysis and experimental validation in our study firmly establishes NNMT as a potential therapeutic target for human cancers. Specifically, targeting NNMT holds promise for the development of innovative and effective cancer treatments. Further investigations into NNMT's role in cancer pathogenesis could potentially pave the way for groundbreaking advancements in cancer treatment.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2730-6011Test

الوصول الحر: https://doaj.org/article/edcf2d327af64be3b719bceec832b69bTest

المؤلفون: Longfei Yang, Yifan Tang, Yuwei Zhang, Yang Wang, Peng Jiang, Fengping Liu, Ninghan Feng

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024)

مصطلحات موضوعية: Pan-cancer analysis, Cuproptosis-related genes, Prognosis, Tumor microenvironment, Drug sensitivity, Medicine, Science

الوصف: Abstract Cuproptosis-related genes (CRGs) are important for tumor development. However, the functions of CRGs across cancers remain obscure. We performed a pan-cancer investigation to reveal the roles of CRGs across cancers. In an analysis of 26 cancers, 12 CRGs were differentially expressed, and those CRGs were found to have prognostic value across different cancer types. The expression of CRGs exhibited varied among tumors of 6 immune subtypes and were significantly correlated with the 16 sensitivities of drugs. The expression of CRGs were highly correlated with immunological subtype and tumor microenvironment (TME) of prostate cancer. We also established CRGs-related prognostic signatures that closely correlated with prognosis and drug sensitivity of prostate cancer patients. Single-cell RNA-seq revealed that several CRGs were enriched in the cancer cells. Finally, an in vitro experiment showed that elesclomol, a cuproptosis inducer, targets ferredoxin 1 and suppress cell viability in prostate cancer cells. In conclusion, we carried out a comprehensive investigation for determining CRGs in differential expression, prognosis, immunological subtype, TME, and cancer treatment sensitivity across 26 malignancies; and validated the results in prostate cancer. Our research improves pan-cancer knowledge of CRGs and identifies more effective immunotherapy strategies.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/07b219d35d584a33a6ae88099bf1db6cTest

المؤلفون: Dongjie Chen, Pengyi Liu, Xiongxiong Lu, Jingfeng Li, Debin Qi, Longjun Zang, Jiayu Lin, Yihao Liu, Shuyu Zhai, Da Fu, Yuanchi Weng, Hongzhe Li, Baiyong Shen

المصدر: Journal of Experimental & Clinical Cancer Research, Vol 43, Iss 1, Pp 1-19 (2024)

مصطلحات موضوعية: Lactate metabolism, Immunotherapy, Survival prognostication, Pan-cancer analysis, scRNA-seq, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy. Methods Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments. Results The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8+ T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy. Conclusions We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-9966Test

الوصول الحر: https://doaj.org/article/77865204698b4594b7d6674ca7230b56Test

المؤلفون: Ren-Hui Xiong, Shuo-Qi Yang, Ji-Wei Li, Xun-kai Shen, Lu-Ming Jin, Chao-Yang Chen, Yu-Ting Yue, Zhi-Chen Yu, Qing-Yu Sun, Wen Jiang, Ming-Zheng Jiang, Xiao-Yan Wang, Shi-Xu Song, Dai Cao, Hong-li Ye, Li-Ran Zhao, Li-Peng Huang, Liang Bu

المصدر: Discover Oncology, Vol 15, Iss 1, Pp 1-21 (2024)

مصطلحات موضوعية: Lung adenocarcinoma, Pan-cancer analysis, Protein tyrosine kinase 6, Experimental validation, Bioinformatics, Prognostic biomarker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. Objective The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. Methods The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. Results PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. Conclusion PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2730-6011Test

الوصول الحر: https://doaj.org/article/ec100f6beb184953a14676866b008603Test

المؤلفون: Hai-hong Shi, Joseph Mugaanyi, Changjiang Lu, Yang Li, Jing Huang, Lei Dai

المصدر: BMC Women's Health, Vol 24, Iss 1, Pp 1-31 (2024)

مصطلحات موضوعية: Glutaminase, Cuproptosis, Pan-cancer analysis, Molecular biomarker, Uterine corpus endometrial carcinoma, Gynecology and obstetrics, RG1-991, Public aspects of medicine, RA1-1270

الوصف: Abstract Background Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. Methods In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. Results Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. Conclusion Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1472-6874Test

الوصول الحر: https://doaj.org/article/52c5340f0f2241b690de1fef9e81f18aTest

المؤلفون: Zi-qiong Wang, Zhi-xuan Wu, Zong-pan Wang, Jing-xia Bao, Hao-dong Wu, Di-yan Xu, Hong-feng Li, Yi-Yin Xu, Rong-xing Wu, Xuan-xuan Dai

المصدر: BMC Cancer, Vol 24, Iss 1, Pp 1-22 (2024)

مصطلحات موضوعية: NUP155, Pan-cancer analysis, Prognosis, Immune infiltration, Immune checkpoints, Molecular biology experiments, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2407Test

الوصول الحر: https://doaj.org/article/afa7cdf948ac4f698bdc4fa7ebf88bb3Test

المؤلفون: Wang X, Bai Y, Wang B

المصدر: Journal of Inflammation Research, Vol Volume 17, Pp 1805-1820 (2024)

مصطلحات موضوعية: cotl1, pan-cancer analysis, cancer therapy, prognosis biomarker, immune cell infiltration., Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950

الوصف: Xiaoyun Wang,1,2 Yuwei Bai,1,2 Bei Wang1,2 1Institute of Integration of Traditional Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of ChinaCorrespondence: Bei Wang, Email xuewuhenwang@126.comBackground: Cancer represents a widespread global health challenge impacting millions of individuals worldwide. Identifying new targets for cancer treatment is a crucial step in developing more effective therapies. Among these potential targets, Coactosin-like protein 1 (COTL1), a cytoskeleton-associated protein with critical roles in cell migration, adhesion, and signaling, has shown involvement in tumor progression.Methods: GSCA, TIMER, SangerBox database were used to explore the COTL1 expression across different tumor types. We employed the TCGA Pan-Atlas Cancer Genomics Dataset, which is available through the cBioportal platform, to explore genetic alterations in COTL1. We conduct a comprehensive analysis of COTL1, encompassing gene expression, clinical prognosis, RNA modification, immunotherapy, and cancer stemness through SangerBox database. Clinical samples were validated using immunohistochemistry.Results: Our analysis revealed that COTL1 is highly expressed in most cancers and correlates with decreased survival in Glioma, Glioblastoma multiforme, and pan-kidney cohorts. Furthermore, COTL1 was found to be associated with DNA and RNA stemness in 20 and 22 different tumor types, respectively. Additionally, COTL1 showed positive correlations with immunological checkpoints and immune infiltration cells. It was also linked to tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1), all of which are potential targets for immunotherapies. Moreover, a favorable relationship was demonstrated between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant allele tumor heterogeneity (MATH) with COTL1. Furthermore, our findings confirmed a positive correlation between COTL1 expression, CD8, and PD-L1 in LGG, as well as an association of high COTL1 expression with decreased patient survival in LGG.Conclusion: Based on these compelling findings, COTL1 may hold significant clinical implications for the development of novel cancer therapies and serve as a potential target for tumors associated with immunotherapy in the future.Keywords: COTL1, pan-cancer analysis, cancer therapy, prognosis biomarker, immune cell infiltration

وصف الملف: electronic resource

العلاقة: https://www.dovepress.com/coactosin-like-protein-1-cotl1-could-be-an-immunological-and-prognosti-peer-reviewed-fulltext-article-JIRTest; https://doaj.org/toc/1178-7031Test

الوصول الحر: https://doaj.org/article/b22a2a6144b046749d550e77717d05ebTest