Human Gene最新文献_第6页

Genomic, transcriptomics, and epigenomic alterations in AREG gene in LUSC and HNSCC LUSC和HNSCC中AREG基因的基因组、转录组学和表观基因组学改变

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-16 DOI: 10.1016/j.humgen.2025.201477

K. Akshaya Krishnan , P. Anitha , J. Vijayashree Priyadharsini , A. Paramasivam

Objectives

Cancers of the head and neck region and lungs share similar risk factors. The increased prevalence of these two cancer types underscores the need to identify diagnostic, therapeutic, and prognostic biomarkers for their management. In this context, the present study aims to identify genetic alterations in the AREG gene and their possible association with HNSCC and LUSC.

Methods

The study employed a computational design, utilizing the following databases and tools to identify the association between disease phenotypes and genes. The cBioPortal database was used to analyze genetic alterations in the AREG gene across TCGA datasets for HNSCC and LUSC. The survival probability and gene expression profile were analyzed using UALCAN. Welch's test demonstrated the statistical significance between the normal and tumor tissues. The microRNA targets of AREG were assessed using the miRDB.

Results

The AREG gene presented with less than 1 % alteration in HNSCC and 4 % in LUSC. Interestingly, a significant upregulation of the AREG gene was observed in HNSCC patients, whereas downregulation was noted in LUSC. The increased gene expression profile correlated well with a poor prognosis in HNSCC patients, while low expression was associated with a good prognosis in LUSC patients. Experimental validation of OSCC samples revealed a decrease in gene expression compared to normal samples. Furthermore, the microRNAs hsa-miR-1185-1 and hsa-miR-487b were identified as potential targets of AREG, influencing the survival of patients with HNSCC.

Conclusions

The overexpression of AREG in HNSCC, along with its poor prognosis, highlights the oncogenic role played by this gene. Interestingly, the epigenetic component, specifically microRNAs hsa-miR-1185-1 and hsa-miR-487b, was found to be downregulated, suggesting their influence on AREG expression. These findings require further validation through functional studies to elucidate the association between AREG and the cancer phenotype.

目的头颈部癌症和肺部癌症具有相似的危险因素。这两种癌症患病率的增加强调了为其管理确定诊断、治疗和预后生物标志物的必要性。在此背景下，本研究旨在确定AREG基因的遗传改变及其与HNSCC和LUSC的可能关联。方法采用计算设计，利用以下数据库和工具来确定疾病表型与基因之间的关系。利用cBioPortal数据库分析了HNSCC和LUSC的TCGA数据集中AREG基因的遗传改变。使用UALCAN分析存活概率和基因表达谱。Welch’s检验显示正常组织与肿瘤组织之间有统计学意义。使用miRDB评估AREG的microRNA靶标。结果AREG基因在HNSCC中变异小于1%，在LUSC中变异小于4%。有趣的是，在HNSCC患者中观察到AREG基因的显著上调，而在LUSC中观察到下调。基因表达谱的升高与HNSCC患者预后不良相关，而低表达与LUSC患者预后良好相关。OSCC样品的实验验证显示，与正常样品相比，基因表达减少。此外，hsa-miR-1185-1和hsa-miR-487b被确定为AREG的潜在靶点，影响HNSCC患者的生存。结论AREG在HNSCC中的高表达，以及其不良预后，突出了该基因的致癌作用。有趣的是，表观遗传成分，特别是microrna hsa-miR-1185-1和hsa-miR-487b被发现下调，这表明它们对AREG表达有影响。这些发现需要通过功能研究进一步验证，以阐明AREG与癌症表型之间的关系。

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引用次数: 0

A novel autosomal dominant variant in TMC1 and rare autosomal recessive variants in GJB2, SLC26A4 caused congenital hearing loss in Vietnamese children 一种新的TMC1常染色体显性变异和罕见的GJB2、SLC26A4常染色体隐性变异导致越南儿童先天性听力损失

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-14 DOI: 10.1016/j.humgen.2025.201480

Phuong Nhung Vu , Hai Ha Nguyen , Thi Huyen Thuong Ma , Thi Bich Ngoc Tran , Thi Kim Phuong Doan , Thi Lan Anh Luong , Tien Truong Dang , Dang Ton Nguyen

Background

Hearing loss in children can lead to consequences such as failure in speech, language, education and poor quality of life. This study investigated five Vietnamese families, one with all three children and others with one child suffered from congenital hearing loss to identify genetic cause of the disease.

Methods and results

Whole exome sequencing was performed for one proband of each family. Subsequently, Sanger sequencing was used for validation the genetic variants in the patients as well as other family members including parents and siblings. A novel variant in TMC1 (c.2209C > T) was detected in the affected child of family 1, which arose as a de novo mutation. In all three affected children of family 2, compound heterozygous variants were detected in SLC26A4 (c.754 T > C, c.1229C > T). In the affected children of family 4 and 5, compound heterozygous of GJB2 (c.109G > A, c.428G > A) and a homozygous deletion in GJB2 (c.235delC) were detected, respectively. In family 3, two genetic variants identified in deafness causing genes MYO7A (c.4795C > T) and MYO15A (c.7547C > T) of the patient in heterozygous state. Sangger sequencing identified only one pathogenic variant in each parent of family 2, 4 and 5. Similarly, existence of double heterozygote in MYO7A/MYO15A was not identified in the parents and remaining unaffected child in family 3.

Conclusions

This study contributed to expand genetic variants spectrum in Vietnamese hearing loss pediatrics. Identifying the genetic causes is crucial for early management of hearing loss patients and giving genetic counseling for further pregnancies of high-risk couples.

儿童听力损失可导致诸如言语、语言、教育和生活质量低下等后果。本研究调查了五个越南家庭，其中一个家庭有三个孩子，另一个家庭有一个孩子患有先天性听力损失，以确定该疾病的遗传原因。方法与结果对每个家族1个先证者进行全外显子组测序。随后，Sanger测序用于验证患者以及其他家庭成员（包括父母和兄弟姐妹）的遗传变异。在家族1的患病儿童中检测到一种新的TMC1变异（c.2209C >； T），这是一种新生突变。在家族2的所有3例患儿中，均检测到SLC26A4的复合杂合变异体（c.754）T >； C, C .1229C >； T)。家族4和家族5患儿分别检测到GJB2复合杂合基因（c.109G >； A, c.428G >； A）和GJB2纯合基因缺失（c.235delC）。在家族3中，在杂合状态患者的致聋基因MYO7A （c.4795C >； T）和MYO15A （c.7547C >； T）中鉴定出两个遗传变异。桑格测序仅在家族2、4和5的每个亲本中发现一个致病变异。同样，在父母和家庭3中未发现MYO7A/MYO15A双杂合子的存在。结论本研究有助于扩大越南听力损失儿科的遗传变异谱。确定遗传原因对于听力损失患者的早期管理和为高危夫妇的进一步怀孕提供遗传咨询至关重要。

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引用次数: 0

Knockdown of histone H1–5 gene affects the sensitivity of MRC-5 and HeLa cells to DNA damaging agents 组蛋白H1-5基因敲低影响MRC-5和HeLa细胞对DNA损伤剂的敏感性

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-12 DOI: 10.1016/j.humgen.2025.201475

Tigran Harutyunyan , Anzhela Sargsyan , Gohar Tadevosyan , Lily Kalashyan , Rouben Aroutiounian , Galina Hovhannisyan

Linker histone H1.5, encoded by the H1–5 gene, plays a key role in chromatin compaction and genome stability. However, its role in cellular responses to mutagens is still poorly understood. Here, we analyzed the genotoxic effects of the standard genotoxic drugs doxorubicin (DOX) and mitomycin C (MMC) at non-cytotoxic concentrations after 24 h of treatment in normal lung fibroblasts (MRC-5) and cervical carcinoma cells (HeLa) with H1–5 gene knockdown (KD). Using CRISPR-Cas9, we achieved significant repression of H1–5 expression. Alkaline DNA comet assay and cytokinesis-block micronucleus assay showed that H1–5 KD significantly increased spontaneous and mutagen-induced DNA and chromosome damage levels in both cell lines (p < 0.05). Our results suggest that H1–5 gene deficiency makes DNA more susceptible to genotoxic impact while its mechanistic role in occurrence of DNA and chromosome damage requires further elucidation.

由H1-5基因编码的连接蛋白H1.5在染色质压实和基因组稳定性中起关键作用。然而，它在细胞对诱变剂反应中的作用仍然知之甚少。在这里，我们分析了标准基因毒性药物多柔比星（DOX）和丝裂霉素C （MMC）在治疗24小时后的非细胞毒性浓度对正常肺成纤维细胞（MRC-5）和H1-5基因敲低（KD）的宫颈癌细胞（HeLa）的遗传毒性作用。使用CRISPR-Cas9，我们实现了H1-5表达的显著抑制。碱性DNA彗星试验和细胞分裂阻滞微核试验显示，H1-5 KD显著增加了两种细胞系的自发和诱变诱导的DNA和染色体损伤水平（p < 0.05）。我们的研究结果表明，H1-5基因缺失使DNA更容易受到遗传毒性的影响，但其在DNA和染色体损伤发生中的机制有待进一步阐明。

引用次数: 0

Single-cell transcriptomics exposes an uncharacterized lncRNA governing colorectal cancer metastasis 单细胞转录组学揭示了一种未表征的lncRNA控制结直肠癌转移

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-12 DOI: 10.1016/j.humgen.2025.201479

Abbas Heydari Lori , Nahid Askari , Hossein Pourghadamyari

Colorectal cancer (CRC) exhibits significant molecular heterogeneity, with long non-coding RNAs (lncRNAs) playing crucial regulatory roles. This study identifies LncRNA01996 as a key oncogenic driver upregulated in CRC tumors compared to adjacent normal tissues, with expression levels correlating directly with advancing cancer stage (Stage I to IV). Mechanistically, LncRNA01996 stabilizes β-catenin, hyperactivating the Wnt signaling pathway while simultaneously suppressing E-CADHERIN expression a critical factor in maintaining cellular adhesion. This dual action promotes cancer cell invasion and metastasis. Additionally, LncRNA01996 transcriptionally activates MYC, amplifying its oncogenic effects.

Clinically, high LncRNA01996 expression is linked to aggressive tumor features, elevated serum markers (CEA, CA19–9), and shorter overall survival in patients. These findings were consistent across patient tissues, cell lines (SW480, SKM), and single-cell RNA sequencing data, confirming its role in diverse CRC microenvironments.

In summary, LncRNA01996 drives CRC progression by dysregulating Wnt/β-catenin signaling, disrupting cell adhesion, and amplifying MYC-driven malignancy. Its strong association with advanced disease and poor outcomes positions LncRNA01996 as a promising prognostic biomarker and a compelling therapeutic target for intercepting CRC metastasis.

结直肠癌（CRC）表现出明显的分子异质性，其中长链非编码rna （lncRNAs）发挥着至关重要的调控作用。本研究确定LncRNA01996是CRC肿瘤中与邻近正常组织相比上调的关键致癌驱动因子，其表达水平与癌症进展（I期至IV期）直接相关。从机制上讲，LncRNA01996稳定β-catenin，过度激活Wnt信号通路，同时抑制E-CADHERIN的表达，这是维持细胞粘附的关键因素。这种双重作用促进了癌细胞的侵袭和转移。此外，LncRNA01996转录激活MYC，放大其致癌作用。在临床上，LncRNA01996的高表达与侵袭性肿瘤特征、血清标志物（CEA、CA19-9）升高和患者总生存期缩短有关。这些发现在患者组织、细胞系（SW480、SKM）和单细胞RNA测序数据中是一致的，证实了其在不同CRC微环境中的作用。总之，LncRNA01996通过失调Wnt/β-catenin信号、破坏细胞粘附和放大myc驱动的恶性肿瘤来驱动结直肠癌的进展。LncRNA01996与晚期疾病和不良预后的强烈关联使其成为一种有前景的预后生物标志物和阻断结直肠癌转移的令人信服的治疗靶点。

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引用次数: 0

Identification of a rare synonymous beta globin variant, HBB: c.60C>T in an Afghan Family as a benign variant 鉴定一种罕见的同义β -珠蛋白变体，HBB: c.60C . >T在阿富汗家庭作为良性变体

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-12 DOI: 10.1016/j.humgen.2025.201481

Zahra Taherian-Esfahani, Hamideh Namazi

Beta thalassemia is a common autosomal recessive disorder. In this study, we report a rare beta globin gene variant, HBB: c.60C>T, identified in an Afghan Family.

Sequencing of a 30 year old pregnant woman and her children showed that this synonymous variant, when present alongside other pathogenic HBB mutations, does not affect beta globin production. In the proband, hematological findings were not consistent with a beta thalassemia minor phenotype. Although this variant has been reported in Clinvar as a variant of uncertain significance (VUS), our findings support its classification as likely benign.

地中海贫血是一种常见的常染色体隐性遗传病。在这项研究中，我们报告了一种罕见的β -珠蛋白基因变异，HBB: c.60C>；T，在一个阿富汗家庭中发现。对一名30岁孕妇及其孩子的测序显示，当与其他致病性HBB突变同时存在时，这种同义变异不影响-珠蛋白的产生。在先证者中，血液学结果与轻度地中海贫血表型不一致。虽然这种变异在Clinvar中被报道为不确定意义变异（VUS），但我们的研究结果支持其分类为可能是良性的。

引用次数: 0

Clinical, genetic, and bioinformatics analysis of a novel TANGO2 mutation (c.263G > A) in an Iranian Azeri Turkish child with lethal metabolic encephalopathy 致死性代谢性脑病伊朗裔阿塞拜疆裔土耳其儿童新型TANGO2突变（c.263G > a）的临床、遗传和生物信息学分析

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-12 DOI: 10.1016/j.humgen.2025.201478

Elnaz Akbari , Asal Asghari Sarfaraz , Mortaza Bonyadi , Mohammad Barzegar

TANGO2-related disorder exhibits significant genotypic and phenotypic heterogeneity, and the clinical significance of novel variants often requires confirmation through detailed case reporting. This case report describes a female child born to consanguineous parents with an unremarkable prenatal and perinatal history. Initial development was normal, but by the second year of life, she exhibited developmental regression, and seizures, which were controlled with levetiracetam. At age 5, she presented with acute encephalopathy, dark urine, rhabdomyolysis, hypoglycemia, and hyperammonemia following a febrile illness. Whole-exome sequencing (WES) identified a novel homozygous TANGO2 variant (c.263G > A, p.Arg88Gln), confirmed via Sanger sequencing, with both parents being heterozygous carriers. Bioinformatics analysis predicted pathogenic effects, including potential exon skipping and protein structural alterations. The variant was absent in 430 ethnically matched controls and major population databases (gnomAD, 1000 Genomes), supporting its pathogenicity. Despite management, the patient experienced recurrent metabolic crises and ultimately succumbed to severe rhabdomyolysis and renal failure at age 8. This case underscores the severe phenotypic consequences of biallelic TANGO2 mutations, including developmental delay, metabolic instability, and early mortality, while highlighting the importance of genetic diagnosis in unexplained pediatric encephalopathies.

tango - 2相关疾病表现出显著的基因型和表型异质性，新变异的临床意义往往需要通过详细的病例报告来证实。本病例报告描述了一个女婴出生的近亲父母与一个不起眼的产前和围产期历史。最初发育正常，但到了第二年，她表现出发育倒退和癫痫发作，用左乙拉西坦控制。5岁时，她表现为急性脑病、尿色深、横纹肌溶解、低血糖和发热性疾病后的高氨血症。全外显子组测序（WES）鉴定出一种新的纯合子TANGO2变异（c.263G > a, p.Arg88Gln），通过Sanger测序证实，父母双方都是杂合子携带者。生物信息学分析预测致病效应，包括潜在的外显子跳变和蛋白质结构改变。在430个种族匹配的对照和主要人群数据库（gnomAD， 1000个基因组）中未发现该变异，支持其致病性。尽管进行了治疗，患者还是经历了反复的代谢危机，最终在8岁时死于严重的横纹肌溶解和肾功能衰竭。该病例强调了双等位基因TANGO2突变的严重表型后果，包括发育迟缓、代谢不稳定和早期死亡，同时强调了基因诊断在不明原因的儿科脑病中的重要性。

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引用次数: 0

Glioma in different life stages: A comparative analysis of adult and pediatric tumors 不同生命阶段的胶质瘤：成人和儿童肿瘤的比较分析

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-10 DOI: 10.1016/j.humgen.2025.201476

Ajia Ashraf , Armeen Ashraf , Lubna Khan , Shahrukh Shaikh , Farina Hanif

Gliomas are one of the most common primary brain tumors and their prognosis is highly dependent on patient-specific factors. The objective of our review is to detail how age influences the epidemiology, molecular pathogenesis, prognosis, and treatment of gliomas. A literature search was conducted for adult and pediatric gliomas (PG) at Google Scholar and PubMed, with relevant keywords like gliomas, World Health Organization (WHO) classification, histology, and treatment, etc., and papers published until 2023 were reviewed. It was found that males and non-Hispanic white people are particularly at risk in both age categories. People with poor socioeconomic status are more likely to have PG. While the overall incidence of adult gliomas has been declining, glioblastoma (GBM) occurrence has been rising. The latest WHO classification of central nervous system (CNS) tumors has highlighted the molecular aberrations to further stratify adult and PG, and literature review revealed how each type has unique histological features. The first line treatment for both groups is surgery followed by adjuvant radio- and chemotherapy, although radiotherapy use for children remains controversial. PGs can also be treated with targeted therapy of the Mitogen-activated protein kinase (MAPK) pathway and currently, anti-cancer drugs are being investigated. By juxtaposing pediatric and adult gliomas, several theories can be proposed about how certain gliomas develop at specific ages, how they vary in their presentations and management, and what can be further explored to improve patient outcomes. This information is pivotal for understanding not only how age influences the development of certain mutations but also how treatment varies according to a patient's age.

胶质瘤是最常见的原发性脑肿瘤之一，其预后高度依赖于患者特异性因素。我们回顾的目的是详细说明年龄如何影响神经胶质瘤的流行病学、分子发病机制、预后和治疗。在谷歌Scholar和PubMed检索成人和儿童胶质瘤（PG）的文献，检索胶质瘤、世界卫生组织（WHO）分类、组织学、治疗等相关关键词，并对2023年之前发表的论文进行综述。研究发现，男性和非西班牙裔白人在这两个年龄段的风险都特别高。社会经济地位较差的人更容易患PG。虽然成人胶质瘤的总体发病率一直在下降，但胶质母细胞瘤（GBM）的发病率一直在上升。WHO对中枢神经系统（CNS）肿瘤的最新分类强调了分子异常，进一步划分成人和PG，文献回顾揭示了每种类型如何具有独特的组织学特征。两组的一线治疗都是手术，然后是辅助放疗和化疗，尽管对儿童使用放疗仍有争议。PGs也可以通过丝裂原活化蛋白激酶（MAPK）途径的靶向治疗来治疗，目前，抗癌药物正在研究中。通过对儿童和成人胶质瘤的对比，可以提出一些关于特定年龄胶质瘤如何发展的理论，它们在表现和处理方面的差异，以及如何进一步探索以改善患者的预后。这些信息不仅对了解年龄如何影响某些突变的发展，而且对了解治疗如何根据患者的年龄而变化至关重要。

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引用次数: 0

Effectiveness of sesamol in alleviating neuroinflammation associated with Parkinson's disease 芝麻酚缓解帕金森病相关神经炎症的有效性

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-08 DOI: 10.1016/j.humgen.2025.201474

Rohini Durairaj , Manjunathan Jagadeesan , S. Shireen Farhana , Shobana Chandrasekar , Usharani Boopathy , Parthiban Brindha Devi , Pasiyappazham Ramasamy

Objectives

A chronic progressive neurodegenerative disorder, Parkinson's disease (PD) is associated with motor impairment with elderly people. The cytokines and chemokines network are very complex and participate to balance the proinflammatory processes, apoptosis and cell existence. So, it is necessary to unravel the inflammatory process in PD. Increased nuclear factor kappa B, expression of cytokines, increased activation of microglia participate in the inflammatory process of PD. The activation of glial fibrillary acidic protein (GFAP) gene and protein results in the activation of astroglial cells which ends up with neurodegeneration and central nervous damage. Natural compounds carry a huge amount of antioxidant properties with health benefits and phenolic compounds is a natural dietary source.

Methods

Quantitative determination of serum CRP, immunohistochemical study was carried out along with the molecular studies such as (RT-PCR) and western blotting.

Results

Sesamol treatment decreased the C- Reactive protein level in serum of experimental animals. Sesamol also increased the tyrosine hydroxylase cells in rotenone-induced animals. The gene and protein expressions of NF-κB (p65), Tumor necrosis factor-α, cyclo oxygeanse-2, inducible nitric oxide synthase, interleukin-1β and GFAP were also reduced in SES treated animals.

Conclusion

Sesamol served as an anti-inflammatory compound in ROT-induced animal model of PD. This work mainly concentrates on the molecular mechanism of phenolic compound sesamol on rotenone induced PD.

目的：帕金森病（PD）是一种慢性进行性神经退行性疾病，与老年人的运动功能障碍有关。细胞因子和趋化因子网络非常复杂，参与平衡促炎过程、细胞凋亡和细胞存在。因此，有必要揭示PD的炎症过程。核因子κ B的增加、细胞因子的表达、小胶质细胞活化的增加参与PD的炎症过程。胶质原纤维酸性蛋白（GFAP）基因和蛋白的激活导致星形胶质细胞的活化，最终导致神经变性和中枢神经损伤。天然化合物具有大量的抗氧化特性，对健康有益，酚类化合物是天然的膳食来源。方法定量测定血清CRP、免疫组化及RT-PCR、western blotting等分子研究。结果沙莫尔降低了实验动物血清C-反应蛋白水平。芝麻酚还能增加鱼藤酮诱导动物的酪氨酸羟化酶细胞。SES处理动物的NF-κB （p65）、肿瘤坏死因子-α、环氧酶-2、诱导型一氧化氮合酶、白细胞介素-1β和GFAP的基因和蛋白表达也降低。结论芝麻酚在rot诱导的PD动物模型中具有抗炎作用。本文主要研究酚类化合物芝麻酚对鱼藤酮诱导PD的分子机制。

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引用次数: 0

The role of a novel m6A reader CSTF2 amplification and overexpression in head and neck cancer development 新型m6A读取器CSTF2扩增和过表达在头颈癌发展中的作用

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-08 DOI: 10.1016/j.humgen.2025.201473

Paramasivam Arumugam , Chandra Pandi , Vijayashree Priyadharsini Jayaseelan

Objective

This study examines the oncogenic role of cleavage stimulation factor subunit 2 (CSTF2), a newly identified N6-methyladenosine (m6A)-binding protein in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). We also explored its amplification-driven overexpression, its prognostic significance, and its mechanistic contributions to tumor aggressiveness.

Method

A dataset of patients with HNSCC was used from the Cancer Genome Atlas (TCGA), which included information on clinical characteristics. Moreover, mRNA and protein expression data of CSTF2 were obtained from the Human Protein Atlas (HPA) database. Additionally, CSTF2 mRNA levels were validated in an independent cohort of HNSCC patient tissues and cell lines using real-time PCR. The prognostic significance of CSTF2 was evaluated using Kaplan-Meier survival plots. Additionally, protein-protein interaction networks of CSTF2 were established using the GeneMANIA database, and functional enrichment analysis was performed with Metascape.

Result

The study demonstrated that the CSTF2 gene was significantly amplified, which correlated with elevated mRNA expression. Moreover, independent cohort analysis confirmed that CSTF2 was overexpressed in HNSCC tissues and cell lines compared to non-tumorous tissues and normal cells. In addition, protein levels were markedly higher in HNSCC tissues, and elevated CSTF2 mRNA expression was associated with poorer overall survival. Functional enrichment analysis showed that CSTF2 is involved in regulating oncogenic processes and the progression of HNSCC.

Conclusion

These data indicate that the CSTF2 gene is amplified and overexpressed in HNSCC, indicating that this gene could be a significant prognostic marker and a potential therapeutic target for HNSCC.

目的探讨新发现的n6 -甲基腺苷（m6A）结合蛋白裂解刺激因子亚单位2 （CSTF2）在头颈部鳞状细胞癌（HNSCC）发病机制中的作用。我们还探讨了其扩增驱动的过表达，其预后意义以及其对肿瘤侵袭性的机制贡献。方法使用来自癌症基因组图谱（TCGA）的HNSCC患者数据集，其中包括临床特征信息。此外，从人类蛋白图谱（Human protein Atlas， HPA）数据库中获得CSTF2 mRNA和蛋白的表达数据。此外，使用实时PCR技术在HNSCC患者组织和细胞系的独立队列中验证了CSTF2 mRNA水平。采用Kaplan-Meier生存图评估CSTF2的预后意义。此外，利用GeneMANIA数据库建立CSTF2蛋白-蛋白相互作用网络，并利用metscape进行功能富集分析。结果CSTF2基因显著扩增，与mRNA表达升高相关。此外，独立队列分析证实，与非肿瘤组织和正常细胞相比，CSTF2在HNSCC组织和细胞系中过表达。此外，HNSCC组织中蛋白质水平明显升高，CSTF2 mRNA表达升高与较差的总生存率相关。功能富集分析表明，CSTF2参与调节HNSCC的癌变过程和进展。结论CSTF2基因在HNSCC中存在扩增和过表达，提示该基因可能是HNSCC的重要预后标志物和潜在的治疗靶点。

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引用次数: 0

Genetic convergence and diversity: A comparative analysis of Egyptian autosomal STR profiles within global populations 遗传趋同和多样性：全球人群中埃及常染色体STR谱的比较分析

IF 0.7 Q4 GENETICS & HEREDITY

Human Gene

Pub Date : 2025-09-06 DOI: 10.1016/j.humgen.2025.201472

Sagy Elzalabany , Ibrahim H. Aboughaleb , Mohamed Hisham Fouad Aref , Tarek Taha , Khaled Amer , Sahar Fawzi , Olfat Shaker

Background and objective

Short Tandem Repeats (STRs) are widely used genetic markers for forensic identification and population genetics due to their high polymorphism. Given Egypt's unique position at the crossroads of Africa, Asia, and Europe, this study aims to analyze the allele frequency distribution of 15 autosomal STR loci in Egyptians and assess their genetic affinities with over 60 other global populations. The objective is to characterize Egypt's genetic profile, evaluate its intra- and inter-regional relationships, and contribute to a broader understanding of global STR clustering.

Methods

Allele frequency data for 15 autosomal STR loci were collected for the Egyptian population and compared with datasets from diverse global populations using Pearson's correlation coefficients, FST genetic distances, and Nei's genetic distance. Hierarchical clustering (UPGMA), allele frequency trajectories (AFTs), and Principal Coordinates Analysis (PCoA) were used to visualize genetic relationships. The findings were contextualized with prior studies of regional genetic structure for completeness and accuracy.

Results

The Egyptian STR profile showed moderate to high correlation (r > 0.85) with Middle Eastern, North African, and Southern European populations. FST and Nei's genetic distance values placed Egypt at a transitional point between Sub-Saharan African and Eurasian clusters. AFT plots revealed several loci with population-specific allele shifts, consistent with historical migration and admixture patterns. Notably, the results aligned with Omran et al.'s finding of genetic divergence between Northern and Southern Egyptians, and supported the tripartite global clustering model described in the 2014 worldwide STR analysis.

Conclusions

Egypt exhibits a unique genetic signature that reflects both African and Eurasian contributions, supporting its role as a genetic bridge population. These findings are valuable for forensic databases, population history, and anthropological studies. Future research should incorporate genome-wide SNP and uniparental marker analyses to further explore Egypt's internal diversity and its broader genetic connections.

背景与目的短串联重复序列（short Tandem Repeats, STRs）因其高多态性而被广泛用于法医鉴定和群体遗传学。鉴于埃及处于非洲、亚洲和欧洲的十字路口的独特位置，本研究旨在分析埃及人15个常染色体STR位点的等位基因频率分布，并评估其与60多个其他全球人群的遗传亲和性。目的是描述埃及的遗传概况，评估其区域内和区域间关系，并有助于更广泛地了解全球STR聚类。方法收集埃及人群15个常染色体STR基因座的等位基因频率数据，并使用Pearson相关系数、FST遗传距离和Nei遗传距离与全球不同人群的数据进行比较。使用分层聚类（UPGMA）、等位基因频率轨迹（AFTs）和主坐标分析（PCoA）来可视化遗传关系。为了完整性和准确性，研究结果与先前的区域遗传结构研究相结合。结果埃及人STR与中东、北非和南欧人群呈中等至高度相关（r > 0.85）。FST和Nei的遗传距离值将埃及置于撒哈拉以南非洲和欧亚集群之间的过渡点。AFT图显示了几个具有群体特异性等位基因转移的位点，与历史迁移和混合模式一致。值得注意的是，这些结果与Omran等人关于埃及北部和南部遗传差异的发现一致，并支持2014年全球STR分析中描述的三方全球聚类模型。结论埃及表现出独特的遗传特征，反映了非洲和欧亚的贡献，支持其作为遗传桥梁群体的作用。这些发现对法医数据库、人口历史和人类学研究都很有价值。未来的研究应结合全基因组SNP和单代标记分析，以进一步探索埃及的内部多样性及其更广泛的遗传联系。

{"title":"Genetic convergence and diversity: A comparative analysis of Egyptian autosomal STR profiles within global populations","authors":"Sagy Elzalabany , Ibrahim H. Aboughaleb , Mohamed Hisham Fouad Aref , Tarek Taha , Khaled Amer , Sahar Fawzi , Olfat Shaker","doi":"10.1016/j.humgen.2025.201472","DOIUrl":"10.1016/j.humgen.2025.201472","url":null,"abstract":"<div><h3>Background and objective</h3><div>Short Tandem Repeats (STRs) are widely used genetic markers for forensic identification and population genetics due to their high polymorphism. Given Egypt's unique position at the crossroads of Africa, Asia, and Europe, this study aims to analyze the allele frequency distribution of 15 autosomal STR loci in Egyptians and assess their genetic affinities with over 60 other global populations. The objective is to characterize Egypt's genetic profile, evaluate its intra- and inter-regional relationships, and contribute to a broader understanding of global STR clustering.</div></div><div><h3>Methods</h3><div>Allele frequency data for 15 autosomal STR loci were collected for the Egyptian population and compared with datasets from diverse global populations using Pearson's correlation coefficients, FST genetic distances, and Nei's genetic distance. Hierarchical clustering (UPGMA), allele frequency trajectories (AFTs), and Principal Coordinates Analysis (PCoA) were used to visualize genetic relationships. The findings were contextualized with prior studies of regional genetic structure for completeness and accuracy.</div></div><div><h3>Results</h3><div>The Egyptian STR profile showed moderate to high correlation (<em>r</em> > 0.85) with Middle Eastern, North African, and Southern European populations. FST and Nei's genetic distance values placed Egypt at a transitional point between Sub-Saharan African and Eurasian clusters. AFT plots revealed several loci with population-specific allele shifts, consistent with historical migration and admixture patterns. Notably, the results aligned with Omran et al.'s finding of genetic divergence between Northern and Southern Egyptians, and supported the tripartite global clustering model described in the 2014 worldwide STR analysis.</div></div><div><h3>Conclusions</h3><div>Egypt exhibits a unique genetic signature that reflects both African and Eurasian contributions, supporting its role as a genetic bridge population. These findings are valuable for forensic databases, population history, and anthropological studies. Future research should incorporate genome-wide SNP and uniparental marker analyses to further explore Egypt's internal diversity and its broader genetic connections.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201472"},"PeriodicalIF":0.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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