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• Research Paper

  m⁶A regulator-mediated methylation modification patterns and tumor immune microenvironment in sarcoma

  Relevance score: 4.977438

  Zhehong Li, Junqiang Wei, Honghong Zheng, Xintian Gan, Mingze Song, Yafang Zhang, Lingwei Kong, Chao Zhang, Jilong Yang, Yu Jin

  Keywords: m⁶A modifications patterns, m⁶A regulators, tumor immune microenvironment (TIME), sarcoma

  Published in Aging on January 3, 2022

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  Background: Studies have shown that the RNA N⁶-methyladenosine (m⁶A) modification patterns are extensively involved in the development of multiple tumors. However, the association between the m⁶A regulator expression patterns and the sarcoma tumor immune microenvironment (TIME) remains unclear.

  Methods: We systematically evaluated the m⁶A regulator expression patterns in patients with sarcoma based on known 23 m⁶A regulators. Different m⁶A regulator expression patterns were analyzed using gene set variation analysis and a single-sample gene set enrichment analysis algorithm. According to the results of consensus clustering, we classified the patients into four different clusters. Next, we subjected the four clusters to differential genetic analysis and established m⁶A-related differentially expressed genes (DEGs). We then calculated the m⁶A-related DEGs score and constructed the m⁶A-related gene signature, named m⁶A score. Finally, the 259 sarcoma samples were divided into high- and low-m⁶A score groups. We further evaluated the TIME landscape between the high- and low-m⁶A score groups.

  Results: We identified four different m⁶A modification clusters and found that each cluster had unique metabolic and immunological characteristics. Based on the 19 prognosis-related DEGs, we calculated the principal component analysis scores for each patient with sarcoma and classified them into high- and low-m⁶A score groups.

  Conclusions: The m⁶A regulator expression patterns and complexity of the sarcoma TIME landscape are closely related to each other. Systematic evaluation of m⁶A regulator expression patterns and m⁶A scores in patients with sarcoma will enhance our understanding of TIME characteristics.

• Research Paper Volume 13, Issue 5 pp 7397-7415

  Prognostic significance of epigenetic regulatory gene expression in patients with non-small-cell lung cancer

  Relevance score: 5.898763

  Zegui Tu, Xiancheng Chen, Tian Tian, Guo Chen, Meijuan Huang

  Keywords: epigenetic regulatory genes, non-small-cell lung cancer, expression patterns, prognosis

  Published in Aging on February 26, 2021

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  In this study, we used public databases to investigate the prognostic significance of epigenetic regulatory gene expression in patients with non small-cell lung cancer (NSCLC). Oncomine database analysis showed that the mRNA levels of seven epigenetic regulatory genes, UHRF1, EZH2, TTF2, SUV39H2, PCNA, WHSC1 and RAD54L, genes were significantly upregulated in NSCLC patients as compared to normal lung tissues. Functional enrichment analysis of these seven genes showed that the most enriched GO terms were DNA repair and rhythmic process, whereas, the most enriched KEGG pathway was lysine degradation pathway. The mRNA and protein expression levels of UHRF1, EZH2, TTF2, WHSC1 and RAD54L significantly correlated with tumor stage in NSCLC patients. Moreover, NSCLC patients exhibiting higher UHRF1, EZH2, WHSC1 and RAD54L mRNA and protein expression levels had poorer progression-free survival and overall survival. These findings demonstrate that UHRF1, EZH2, WHSC1 and RAD54L are potential prognostic biomarkers to distinguish high-risk from low-risk NSCLC patients.

• Research Paper Volume 8, Issue 11 pp 2635-2654

  Distinct patterns of simple sequence repeats and GC distribution in intragenic and intergenic regions of primate genomes

  Relevance score: 6.436975

  Wen-Hua Qi, Chao-chao Yan, Wu-Jiao Li, Xue-Mei Jiang, Guang-Zhou Li, Xiu-Yue Zhang, Ting-Zhang Hu, Jing Li, Bi-Song Yue

  Keywords: Simple sequence repeats, GC, genomic regions, patterns, primate genomes

  Published in Aging on September 16, 2016

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  As the first systematic examination of simple sequence repeats (SSRs) and guanine-cytosine (GC) distribution in intragenic and intergenic regions of ten primates, our study showed that SSRs and GC displayed nonrandom distribution for both intragenic and intergenic regions, suggesting that they have potential roles in transcriptional or translational regulation. Our results suggest that the majority of SSRs are distributed in non-coding regions, such as the introns, TEs, and intergenic regions. In these primates, trinucleotide perfect (P) SSRs were the most abundant repeats type in the 5'UTRs and CDSs, whereas, mononucleotide P-SSRs were the most in the intron, 3'UTRs, TEs, and intergenic regions. The GC-contents varied greatly among different intragenic and intergenic regions: 5'UTRs > CDSs > 3'UTRs > TEs > introns > intergenic regions, and high GC-content was frequently distributed in exon-rich regions. Our results also showed that in the same intragenic and intergenic regions, the distribution of GC-contents were great similarity in the different primates. Tri- and hexanucleotide P-SSRs had the most GC-contents in the 5'UTRs and CDSs, whereas mononucleotide P-SSRs had the least GC-contents in the six genomic regions of these primates. The most frequent motifs for different length varied obviously with the different genomic regions.

  

  SSRs abundance of six categories in different intragenic and intergenic regions of primates. ABCDEF represent 5'UTRs, CDSs, introns, 3'UTRs, TEs, and intergenic regions, respectively.

  
  
  

  

  The distribution of SSRs in ten primate genomes. Percentages were calculated according to the total number of each SSR category divided by the total number of SSRs for that organism.

  
  
  

  

  Relative abundance of mono- to trinucleotide P-SSRs in different intragenic and intergenic regions of ten primates. ABCDEF represent 5'UTRs, CDSs, introns, 3'UTRs, TEs, and intergenic regions, respectively.

  
  
  

  

  Relative abundance of mono- to hexanucleotide P-SSRs in different intragenic and intergenic regions of ten primates. ABCDEF represent 5'UTRs, CDSs, introns, 3'UTRs, TEs, and intergenic regions, respectively.

  
  
  

  

  GC-content of different intragenic and intergenic regions in ten primates.

  
  
  

  

  GC-content of mono- to hexanucleotide P-SSRs in different intragenic and intergenic regions of ten primates. ABCDEF represent 5'UTRs, CDSs, introns, 3'UTRs, TEs, and intergenic regions, respectively.

  
  
  

• Research Paper pp undefined-undefined

  Pyroptosis patterns of colon cancer could aid to estimate prognosis, microenvironment and immunotherapy: evidence from multi-omics analysis

  Relevance score: 6.401277

  Jing Zhou, Hao Guo, Likun Liu, Mali Feng, Xihua Yang, Shulan Hao

  Keywords: colon cancer, tumor microenvironment, pyroptosis patterns, immunotherapy, the cancer genome atlas

  Published in Aging on Invalid Date

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  Pyroptosis plays a critical role in the occurrence and development of colon cancer (CC). However, the specific mechanisms of pyroptosis patterns on immune regulation and tumor microenvironment (TME) formation in CC remain unclear. Based on 30 pyroptosis-related genes (PRGs), we evaluated the pyroptosis patterns of 1689 CC samples from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The signatures of pyroptosis patterns and PRGs were identified in CC. In addition to systematically associating these patterns with TME cell infiltration characteristics, we constructed a pyroptosis signature score (PPSscore) to quantify pyroptosis patterns in individual tumor patients with immune responses. We discovered three distinct pyroptosis patterns, each with a different survival probability and being biologically relevant. TME infiltrating characteristics of revealed these patterns, consistent with immune-inflamed, immune-desert and immune-excluded phenotypes. Furthermore, a low PPSscore was associated with better clinical benefits. A high PPSscore was associated with a lower chance of survival due to its association with stromal activation. Additionally, two immunotherapy cohorts revealed that patients with lower PPSscore had better immune responses and durable clinical benefits. Our findings indicate that pyroptosis patterns play a vital role in immunoregulation and the formation of TME in CC.

• Research Paper pp undefined-undefined

  Generating detailed intercellular communication patterns in psoriasis at the single-cell level using social networking, pattern recognition, and manifold learning methods to optimize treatment strategies

  Relevance score: 5.2619786

  Ying Xiong, Sidi Li, Yunmeng Bai, Ting Chen, Wenwen Sun, Lijie Chen, Jia Yu, Liwei Sun, Chijun Li, Jiajian Wang, Bo Wu

  Keywords: communication patterns, single cell transcriptome, cell type-specific regulons (CTSRs), proteomic sequencing, social networking

  Published in Aging on Invalid Date

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  Psoriasis, a complex and recurrent chronic inflammatory skin disease involving various inflammatory cell types, requires effective cell communication to maintain the homeostatic balance of inflammation. However, patterns of communication at the single-cell level have not been systematically investigated. In this study, we employed social network analysis tools, pattern recognition, and manifold learning to compare molecular communication features between psoriasis cells and normal skin cells. Utilizing a process that facilitates the discovery of cell type-specific regulons, we analyzed internal regulatory networks among different cells in psoriasis. Advanced techniques for the quantitative detection of non-targeted proteins in pathological tissue sections were employed to demonstrate protein expression. Our findings revealed a synergistic interplay among the communication signals of immune cells in psoriasis. B-cells were activated, while Langerhans cells shifted into the primary signaling output mode to fulfill antigen presentation, mediating T-cell immunity. In contrast to normal skin cells, psoriasis cells shut down numerous signaling pathways, influencing the balance of skin cell renewal and differentiation. Additionally, we identified a significant number of active cell type-specific regulons of resident immune cells around the hair follicle. This study unveiled the molecular communication features of the hair follicle cell-psoriasis axis, showcasing its potential for therapeutic targeting at the single-cell level. By elucidating the pattern of immune cell communication in psoriasis and identifying new molecular features of the hair follicle cell-psoriasis axis, our findings present innovative strategies for drug targeting to enhance psoriasis treatment.

• Research Paper pp undefined-undefined

  Treatment patterns and survival in T4b esophageal cancer: a retrospective cohort study

  Relevance score: 7.460335

  Bin-Bin Yu, Jiang-Qiong Huang, Huan-Wei Liang, Yang Liu, Long Chen, Su Pei, Wei Huang, Xin-Bin Pan

  Keywords: esophageal cancer, T4b, treatment patterns, survival

  Published in Aging on Invalid Date

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  Purpose: This study aims to evaluate the efficacy of various treatment approaches in stage T4b esophageal cancer patients.

  Materials and methods: Data were extracted from the Surveillance, Epidemiology, and End Results databases, covering patients diagnosed with esophageal cancer between 2000 and 2020. Kaplan-Meier analysis was used to assess cancer-specific survival (CSS) and overall survival (OS) across different treatment patterns.

  Results: The study included 482 patients: 222 (46.1%) received chemoradiotherapy, 58 (12.0%) underwent radiotherapy alone, 37 (7.7%) received chemotherapy alone, 50 (10.4%) underwent surgery, and 115 (23.8%) received no treatment. Median CSS were 12, 4, 6, 18, and 1 month for chemoradiotherapy, radiotherapy alone, chemotherapy alone, surgery, and non-treatment groups. Median OS for these groups were 11, 3, 6, 17, and 1 month, respectively. Multivariable proportional hazard regression analysis revealed that patients who underwent surgery experienced significantly improved CSS (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.24-0.72; P = 0.002) and OS (HR = 0.45, 95% CI: 0.28-0.74; P = 0.002) compared to those receiving chemoradiotherapy after propensity score matching.

  Conclusions: Esophagectomy, with or without radiotherapy and/or chemotherapy, results in better survival outcomes than chemoradiotherapy in patients with stage T4b esophageal cancer.