Cancer Genetics最新文献_第7页

The mechanism of lncRNA SSTR5-AS1 promoting ferroptosis resistance and immune escape in ovarian cancer cells by recruiting STAT3 to regulate SLC7A11 expression lncRNA SSTR5-AS1通过募集STAT3调控SLC7A11表达促进卵巢癌细胞耐铁凋亡和免疫逃逸的机制

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-16 DOI: 10.1016/j.cancergen.2025.07.009

Qiong Wei , Yi Yang , Huimin Wang, Chun Li, Yuping Li

Objective

Ovarian cancer (OC) is the foremost cause of gynecological cancer-related mortality. Respecting the role of long noncoding RNAs (lncRNAs) in malignancies, we explored the mechanism of SSTR5-AS1 regulating OC cell ferroptosis resistance and immune escape via the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7a member 11 (SLC7A11) axis.

Methods

OC cells were treated with si-SSTR5-AS1, oe-SSTR5-AS1 and oe-SLC7A11 plasmids. SSTR5-AS1, STAT3 and SLC7A11 mRNA levels, and cell malignant behaviors were assessed by RT-qPCR, CCK-8 and Transwell assays. Fe²⁺, glutathione (GSH) and malondialdehyde (MDA) levels in Erastin-induced OC cells, and viability and apoptosis in OC cell-co-cultured CD8⁺T cells were determined using kits, and CCK-8 and flow cytometry. SSTR5-AS1 distribution was detected by subcellular fractionation assay. STAT3 and SLC7A11 protein levels were measured by Western blot. The protein interaction and binding relationship between SSTR5-AS1 and STAT3 were predicted by database and confirmed using RIP and verified using dual-luciferase assays.

Results

SSTR5-AS1 was up-regulated in OC cells. SSTR5-AS1 overexpression facilitated OC cell malignant behaviors, down-regulated Fe²⁺ and MDA levels and up-regulated the GSH level in Erastin-treated OC cells, and diminished viability and enhanced apoptosis in OC cell-co-cultured CD8⁺T cells, suggesting that SSTR5-AS1 overexpression promoted OC cell ferroptosis resistance and immune escape, which were inhibited by its downregulation. SSTR5-AS1 facilitated SLC7A11 transcription and expression by recruiting STAT3. SLC7A11 overexpression partially reversed the effects of SSTR5-AS1 knockdown on OC cells.

Conclusion

SSTR5-AS1 promoted SLC7A11 transcription and expression by recruiting STAT3, thereby promoting ferroptosis resistance and immune escape of OC cells.

目的卵巢癌（OC）是妇科肿瘤相关死亡的首要原因。考虑到长链非编码rna （lncRNAs）在恶性肿瘤中的作用，我们探索了SSTR5-AS1通过转录3信号换能器和激活器(STAT3)/溶质载体家族7a成员11 （SLC7A11）轴调控OC细胞铁凋亡抵抗和免疫逃逸的机制。方法采用si-SSTR5-AS1、oe-SSTR5-AS1和oe-SLC7A11质粒处理soc细胞。采用RT-qPCR、CCK-8、Transwell检测SSTR5-AS1、STAT3、SLC7A11 mRNA表达水平及细胞恶性行为。采用试剂盒、CCK-8和流式细胞术检测erastin诱导OC细胞中Fe2+、谷胱甘肽（GSH）和丙二醛（MDA）水平，以及OC细胞共培养CD8+T细胞的活力和凋亡。亚细胞分离法检测SSTR5-AS1的分布。Western blot检测STAT3和SLC7A11蛋白水平。通过数据库预测SSTR5-AS1和STAT3之间的蛋白相互作用和结合关系，并通过RIP和双荧光素酶实验进行验证。结果ssstr5 - as1在OC细胞中表达上调。SSTR5-AS1过表达可促进OC细胞的恶性行为，下调erastin处理OC细胞的Fe2+和MDA水平，上调GSH水平，降低OC细胞共培养CD8+T细胞的活力，增强凋亡，提示SSTR5-AS1过表达促进OC细胞对铁凋亡的抵抗和免疫逃逸，而这一过程被其下调抑制。SSTR5-AS1通过募集STAT3促进SLC7A11的转录和表达。SLC7A11过表达部分逆转了SSTR5-AS1敲低对OC细胞的影响。结论sstr5 - as1通过募集STAT3促进SLC7A11的转录和表达，从而促进OC细胞对铁下垂的抵抗和免疫逃逸。

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引用次数: 0

The effect of HOTAIR gene variants on the development of bladder cancer and its clinicopathological characteristics in a Caucasian population HOTAIR基因变异对白种人膀胱癌发展及其临床病理特征的影响

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-10 DOI: 10.1016/j.cancergen.2025.07.007

Yakup Akkoç , Hasan Sulhan , Ersin Akgöllü , Ali Çift

Background

The age-adjusted rate of Bladder cancer (BC) in Türkiye is quite high, and genetic factors are effective in BC. Long non-coding RNAs (lncRNAs) synthesized from the HOTAIR gene have been shown to promote tumor progression in many cancers. rs874945 and rs4759314 polymorphisms in the HOTAIR gene cause changes in the expression levels of lncRNAs synthesized from this gene. The aim of this study was to explore for the first time the association of these variants with BC in a Caucasian population.

Methods

The present study explored the HOTAIR gene polymorphisms in 98 BC patients and in 150 healthy individuals using real-time polymerase chain reaction (RT-PCR).

Results

Carrying rs874945 G allele and GA genotype increased the BC risk in the statistic models. However, even if rs4759314 variant increased of BC risk was not significant. Similarly, although both polymorphisms increased clinicopathological features associated with poor prognosis, they were not statistically significant. Moreover, being older than 60 years and smoking are independent risk factors for BC.

Discussion

The current study is the first to show that patients carrying the G allele of the rs874945 polymorphism have a higher risk of BC in the Caucasian population. This work suggests that rs4759314 polymorphism should be studied in the Caucasian population with a larger sample size of BC patients.

背景：基耶人膀胱癌（BC）的年龄调整率相当高，遗传因素在BC中起作用。由HOTAIR基因合成的长链非编码rna （lncRNAs）已被证明在许多癌症中促进肿瘤进展。HOTAIR基因的rs874945和rs4759314多态性导致由该基因合成的lncrna表达水平发生变化。本研究的目的是首次探索这些变异与高加索人群中BC的关系。方法采用实时聚合酶链反应（RT-PCR）对98例BC患者和150例健康人群的HOTAIR基因多态性进行分析。结果在统计模型中，携带rs874945 G等位基因和GA基因型增加了BC的风险。然而，即使rs4759314变异增加BC风险也不显著。同样，尽管这两种多态性增加了与预后不良相关的临床病理特征，但它们没有统计学意义。此外，年龄超过60岁和吸烟是BC的独立危险因素。目前的研究首次表明，携带rs874945多态性的G等位基因的患者在高加索人群中患BC的风险更高。这项工作表明，rs4759314多态性应该在样本量较大的BC患者的高加索人群中进行研究。

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引用次数: 0

Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach PIK3CA畸变在癌症类型中的患病率和临床意义：一种真实世界的下一代测序方法

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-09 DOI: 10.1016/j.cancergen.2025.07.006

Junkyu Kim , Hye-Lim Jang , Jung Young Hong , Seung Tae Kim , Se Hoon Park , Joon Oh Park , Kyoung-Mee Kim , Deok geun Kim , Jeeyun Lee , Sung Hee Lim

Background

Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the PIK3CA gene. Recent advancements have shown effective treatment for patients with PIK3CA-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.

Methods

From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3886 patients with 36 different cancer types at the Samsung Medical Center. The incidence of PIK3CA mutations and amplifications according to cancer type and their correlation with the tumor mutation burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) status were reviewed. Mutation sites were also identified.

Results

Among the 3886 patients, PIK3CA mutations were present in 9.2 % (358/3886) of the cohort, with colorectal cancer, 52.8 % (189/358), having the highest incidence. Patients harboring PIK3CA mutations demonstrated significantly higher TMB and MSI-high rates than those without (31.8 % vs. 12.5 % for TMB and 7.8 % vs. 1.6 % for MSI-high, respectively, p = 0.001). In contrast, PIK3CA amplifications were observed in 1.3 % (51/3886) of patients, primarily in gastric, bladder, and colorectal cancers, and associated with lower TMB, MSI-high, and HRD rates. PIK3CA fusions were identified in three patients. The most common mutation sites were E545K, E542K, and H1047R.

Conclusion

Of 3886 patients with metastatic solid tumors, 358(9.2 %) had PIK3CA mutations and 51(1.3 %) had PIK3CA amplifications. Next-generation sequencing analysis provided a deeper understanding of PIK3CA aberrations.

磷脂酰肌醇3-激酶（PI3K）途径的激活是各种实体肿瘤中常见的致癌机制，通常由PIK3CA基因畸变驱动。最近的进展表明pik3ca突变乳腺癌患者的有效治疗；然而，对其他恶性肿瘤的需求尚未得到满足。这项研究的目的是为了更好地了解PIK3CA突变和不同癌症类型的扩增。方法2019年10月至2023年6月，利用Trusight Oncology 500对三星首尔医院36种不同癌症类型的3886例患者进行了新一代测序。本文综述了PIK3CA突变和扩增的发生率及其与肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和同源重组缺陷（HRD）状态的相关性。突变位点也被确定。结果3886例患者中，PIK3CA突变发生率为9.2%(358/3886)，其中结直肠癌发生率最高，为52.8%（189/358）。携带PIK3CA突变的患者TMB和MSI-high的发生率明显高于未携带PIK3CA突变的患者（分别为31.8% vs 12.5% TMB和7.8% vs 1.6% MSI-high, p = 0.001）。相比之下，在1.3%（51/3886）的患者中观察到PIK3CA扩增，主要是在胃癌，膀胱癌和结直肠癌中，并且与较低的TMB， MSI-high和HRD发生率相关。在3例患者中发现了PIK3CA融合。最常见的突变位点为E545K、E542K和H1047R。结论3886例转移性实体瘤患者中，358例（9.2%）存在PIK3CA突变，51例（1.3%）存在PIK3CA扩增。下一代测序分析提供了对PIK3CA畸变更深入的了解。

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引用次数: 0

Upregulation of Uracil DNA Glycosylase (UNG) in Prostate Cancer 尿嘧啶DNA糖基化酶（UNG）在前列腺癌中的上调

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-07 DOI: 10.1016/j.cancergen.2025.07.005

Vahid Rouhi , Sanaz Habibi , Dr. Hikmet Koseoglu , Dr. Emre Ari , Mehmet Guven

Prostate cancer is the second most common malignancy and a major cause of cancerrelated deaths in men. Dysregulation of DNA repair mechanisms, particularly those involved in base excision repair (BER), contributes significantly to carcinogenesis. Alterations in this pathway have been linked to aggressive tumor behavior, early recurrence, and poor survival, positioning DNA repair as a promising therapeutic target. This study focused on the expression of two BER genes, uracil DNA glycosylase (UNG) and 8-oxoguanine DNA glycosylase (OGG1), in tumor and adjacent normal prostate tissues. Fifty prostate cancer patients were enrolled. Tumor and adjacent normal tissues were obtained using tru-cut biopsy. Gene expression levels of UNG and OGG1 were assessed by quantitative real-time PCR. UNG expression was significantly elevated in tumor tissues compared to normal tissues, showing a 3.39-fold increase (p = 0.02). OGG1 expression also increased by 2.60-fold, but this was not statistically significant (p > 0.05). A positive correlation was observed between UNG expression and PSA levels in tumor tissues (r = 0.341, p = 0.01). No statistically significant difference in gene expression was found between tumor and normal tissues with respect to clinical parameters such as diabetes, hypertension, PIRADS score, Gleason score, smoking status, or presence of nodules. UNG is significantly upregulated in prostate cancer and may help maintain genomic stability and tumor cell survival. Targeting UNG alongside DNA-damaging therapies could disrupt cancer progression. Further studies on BER genes may support personalized treatment approaches in prostate cancer.

前列腺癌是第二常见的恶性肿瘤，也是男性癌症相关死亡的主要原因。DNA修复机制的失调，特别是涉及碱基切除修复（BER）的DNA修复机制的失调，对癌症的发生起着重要的作用。这一通路的改变与肿瘤的侵袭性行为、早期复发和较差的生存率有关，这使得DNA修复成为一个有希望的治疗靶点。本研究重点研究了尿嘧啶DNA糖基化酶（UNG）和8-氧鸟嘌呤DNA糖基化酶（OGG1）两个BER基因在肿瘤和邻近正常前列腺组织中的表达。50名前列腺癌患者被纳入研究。采用真切活检法获得肿瘤及邻近正常组织。采用实时荧光定量PCR检测UNG和OGG1基因表达水平。与正常组织相比，UNG在肿瘤组织中的表达明显升高，为3.39倍（p = 0.02）。OGG1表达量也增加了2.60倍，但差异无统计学意义(p >；0.05)。肿瘤组织中UNG表达与PSA水平呈正相关（r = 0.341, p = 0.01）。在临床参数如糖尿病、高血压、PIRADS评分、Gleason评分、吸烟状况或结节的存在等方面，肿瘤组织与正常组织的基因表达无统计学差异。UNG在前列腺癌中显著上调，可能有助于维持基因组稳定性和肿瘤细胞存活。靶向UNG和dna损伤疗法可能会破坏癌症的进展。对BER基因的进一步研究可能支持前列腺癌的个性化治疗方法。

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引用次数: 0

Tandem duplication and triplication in BRCA1: revisiting the large genomic rearrangements via optical genome mapping BRCA1的串联重复和三次重复：通过光学基因组定位重新审视大基因组重排

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-07 DOI: 10.1016/j.cancergen.2025.07.002

B Aldrige Allister , Jonathan L Lühmann , Lena Wendeburg , Frank Dechend , Carmela Beger , Stefanie Tölle , Julia von Ehr , Tim Ripperger , Bernd Auber , Nataliya di Donato , Doris Steinemann

Large genomic rearrangements (LGRs) within the human genome are becoming more recognized by novel genome-wide technologies and may be underreported so far. This class of genomic variation includes copy number variations like duplications or triplications of coding or non-coding genomic regions. Here, we report two LGRs targeting BRCA1, a duplication of exons 18–19 and a triplication of exons 1–2 in two independent families. Utilizing Optical Genome Mapping (OGM), Whole Genome Sequencing (WGS) and cDNA analysis, we characterized the genomic organization and transcriptomic effects of these LGRs regarding its. We show that the tandem duplication ogm[GRCh38]dup(17)(q21.31q21.31)(43057052_43063373), targeting BRCA1 exon 18–19 is predicted to generate a premature termination codon, namely p.(His1732Metfs*10). The triplication of BRCA1 exon 1–2 ogm[GRCh38]trip(17)(q21.31q21.31)(43117155_43124115) is also sequentially arranged. The transcript shows an insertion of a small part of intron 2 (chr17:43,121,558–43,121,676) that theoretically will generate a premature termination codon as well. Collectively, OGM and WGS help elucidating the architecture of these LGRs. However, the final curation depends on how adequate the functional consequences of these LGR can be clarified. Deeper investigation of LGRs on transcript level is important to attain accurate conclusions with respect to therapeutic decisions.

人类基因组内的大基因组重排（lgr）越来越被新的全基因组技术所认识，但迄今为止可能被低估。这类基因组变异包括拷贝数变异，如编码或非编码基因组区域的重复或三倍。在这里，我们报告了两个靶向BRCA1的lgr，两个独立家族的外显子18-19的重复和外显子1-2的三倍。利用光学基因组图谱（OGM）、全基因组测序（WGS）和cDNA分析，研究了这些lgr的基因组组织和转录组效应。我们发现，靶向BRCA1外显子18-19的串联重复ogm[GRCh38]dup(17)(q21.31q21.31)（43057052_43063373）预计会产生一个过早终止密码子，即p.（His1732Metfs*10）。BRCA1外显子1-2 ogm[GRCh38]trip(17)(q21.31q21.31)（43117155_43124115）也是按顺序排列的。转录本显示插入了内含子2的一小部分（chr17:43,121,558-43,121,676），理论上也会产生一个过早终止密码子。总的来说，OGM和WGS有助于阐明这些lgr的体系结构。然而，最终的管理取决于这些LGR的功能后果如何得到充分的澄清。在转录水平上对lgr进行更深入的研究对于获得有关治疗决策的准确结论至关重要。

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引用次数: 0

TFAP2E acts as a tumor suppressor by regulating cell cycle progression in oral squamous cell carcinoma cells TFAP2E通过调节口腔鳞状细胞癌细胞周期进程发挥抑瘤作用

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-05 DOI: 10.1016/j.cancergen.2025.07.004

Ryo Sakai , Yoshinori Inagaki , Haruno Tsurumi , Akiko Ohashi , Tadateru Takayama , Shuichi Sato , Kyoko Fujiwara

TFAP2E, a member of the activator protein-2 transcription factor family, is considered to act as a tumor suppressor. Lower TFAP2E expression is associated with poor prognosis in patients with different cancer types. TFAP2E gene is located on chromosome 1q34, where is commonly deleted region in the cancer genome. Our previous research indicated that TFAP2E suppresses cell growth by regulating cell cycle progression from the G2 to M phase. However, as the analyses were performed using asynchronized cells, other possibilities cannot be ruled out. The present study aimed to analyze the effects of TFAP2E silencing on synchronized cells. Human oral squamous cell carcinoma (OSCC)-derived Ca9–22 cells were stably transfected with TFAP2E-short hairpin RNA and synchronized to the late-G1 phase using double thymidine block. Cell cycle progression rate was analyzed by periodically examining cell cycle distribution patterns using fluorescence-activated cell sorting analysis. TFAP2E-knockdown cells showed a rapid exit from the M-phase compared with control cells; meanwhile, no difference was observed between the cells until the end of S-phase. Additionally, rapid M-phase exit was not observed in TFAP2E-knockdown cells following release from nocodazole-mediated synchronization to the G2/M-phase. These observations indicated that TFAP2E-knockdown results in rapid cell cycle progression from the G2 to M phase. Overall, current findings suggest that TFAP2E acts as a tumor suppressor by regulating cell cycle progression at least in OSCC cells.

TFAP2E是激活蛋白-2转录因子家族的成员，被认为具有肿瘤抑制作用。TFAP2E低表达与不同癌症类型患者预后不良相关。TFAP2E基因位于染色体1q34上，这是癌症基因组中常见的缺失区域。我们之前的研究表明，TFAP2E通过调节细胞周期从G2期到M期的进程来抑制细胞生长。然而，由于分析是使用异步单元执行的，因此不能排除其他可能性。本研究旨在分析TFAP2E沉默对同步细胞的影响。用tfap2e短发夹RNA稳定转染人口腔鳞状细胞癌（OSCC）来源的Ca9-22细胞，并使用双胸腺嘧啶阻断使其同步到g1晚期。通过荧光活化细胞分选分析定期检查细胞周期分布模式来分析细胞周期进展率。与对照细胞相比，tfap2e敲低细胞能快速退出m期；同时，直到s期结束，细胞间均无差异。此外，在tfap2e敲低的细胞中，从诺可达唑介导的同步释放到G2/ m期后，没有观察到快速退出m期。这些观察结果表明，tfap2e敲低导致细胞周期从G2期快速进展到M期。总的来说，目前的研究结果表明，至少在OSCC细胞中，TFAP2E通过调节细胞周期进程发挥肿瘤抑制作用。

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引用次数: 0

Detection of VHL variant on multigene panel testing for hereditary breast cancer: Implications for genetic counselling 遗传性乳腺癌的多基因面板检测VHL变异：遗传咨询的意义

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-05 DOI: 10.1016/j.cancergen.2025.07.003

Jennifer YM Ling , Kirk AJ Stephenson , Tammy L Romanuik , My Linh Thibodeau , Maryam Soleimani , Katherine E Paton

As multigene panel genetic testing for hereditary cancer syndromes increases in clinical use, the detection of unexpected secondary findings will occur more commonly. We present the case of a 40-year-old woman with breast cancer who harboured a secondary finding in the VHL gene variant without other cancer risk alleles (e.g., BRCA1/BRCA2) sufficient to explain her primary presentation. Subsequent exam revealed ophthalmic manifestations of von Hippel-Lindau syndrome (VHLS), emphasizing the importance of multidisciplinary clinical assessment and phenotyping. The development of retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumours and phaeochromocytomas are characteristic of VHLS, but the link with breast cancer is poorly understood. Though the benefit of hereditary cancer genetic testing is well-known, this case highlights the importance of pre-test genetic counselling to prepare patients for all possible results, including additional unanticipated genetic diagnoses. Such pre-test counselling can set appropriate expectations for the possible requirement of ongoing surveillance and/or treatment.

随着遗传性癌症综合征的多基因面板基因检测在临床应用的增加，意外的继发性发现将更常见。我们报告了一名40岁的乳腺癌女性，她在没有其他癌症风险等位基因（如BRCA1/BRCA2）的VHL基因变异中发现了继发性发现，足以解释她的原发性表现。随后的检查显示von Hippel-Lindau综合征（VHLS）的眼部表现，强调多学科临床评估和表型的重要性。视网膜和中枢神经系统血管母细胞瘤、透明细胞肾细胞癌、胰腺神经内分泌肿瘤和嗜铬细胞瘤的发展是VHLS的特征，但与乳腺癌的联系尚不清楚。虽然遗传性癌症基因检测的好处是众所周知的，但这个病例强调了检测前遗传咨询的重要性，以使患者为所有可能的结果做好准备，包括额外的意外遗传诊断。这种测试前咨询可以为持续监测和/或治疗的可能需求设定适当的期望。

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引用次数: 0

Influence of IL-38 as a novel biomarker on the pathophysiological processes of esophageal cancer IL-38作为新型生物标志物对食管癌病理生理过程的影响

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-03 DOI: 10.1016/j.cancergen.2025.06.010

Dehua Zeng , Shixin Ye , Wenmin Yin , Duohuang Lian , Shunkai Zhou

Objective

This study aimed to identify biomarkers of esophageal cancer and elucidate their mechanisms of action in esophageal cancer.

Methods

Differential protein expression between esophageal tumor tissue and adjacent normal tissue was analyzed using proteomics in a mouse model of esophageal cancer. Differential proteins were identified through bioinformatics analysis. The mechanisms of action of differential proteins in esophageal cancer were validated using techniques such as western blotting and immunohistochemistry.

Results

Proteomic analysis revealed that IL-38 exhibited the greatest differential expression. Molecular biology techniques including western blotting and immunohistochemistry demonstrated that IL-38 modulates Regulatory T cell (Treg)/ T helper 17 cell (Th17) balance through the Sirtuin 1 (SIRT1)/ hypoxia-inducible factor 1-alpha (HIF-1α) signaling pathway in esophageal cancer.

Conclusion

IL-38 is a novel biomarker for esophageal cancer and regulates Treg/Th17 balance through the Sirt1/HIF-1α signaling pathway, providing new insights for the treatment of esophageal cancer.

目的鉴定食管癌的生物标志物，探讨其在食管癌中的作用机制。方法采用蛋白质组学方法分析食管癌小鼠模型中食管癌组织与邻近正常组织的蛋白表达差异。通过生物信息学分析鉴定差异蛋白。利用western blotting和免疫组织化学等技术验证了差异蛋白在食管癌中的作用机制。结果蛋白质组学分析显示IL-38的表达差异最大。western blotting和免疫组化等分子生物学技术表明，IL-38通过SIRT1 / HIF-1α信号通路调节食管癌中调节性T细胞(Treg)/辅助性T细胞（Th17）的平衡。结论il -38是食管癌的新型生物标志物，通过Sirt1/HIF-1α信号通路调控Treg/Th17平衡，为食管癌的治疗提供新的思路。

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引用次数: 0

ADAR1 gene expression and its importance in breast cancer ADAR1基因表达及其在乳腺癌中的意义

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-07-01 DOI: 10.1016/j.cancergen.2025.06.011

Bulent Tekin , Seda Ekizoglu , Sare Burcu Kaya , Mehmet Guven , Didem Can Trabulus

RNA editing mediated by ADAR1 is vital for the survival of mammals, and its malfunction leads to irregular editing of its targets, potentially influencing the observable characteristics of breast cancer. The study aims to investigate ADAR1- p110 and ADAR1-p150 gene expression in breast cancer patients' tissue samples (tumor and normal), to determine the role of this expression in tumor development, and to correlate expression levels with patients' clinical findings to understand breast cancer heterogeneity. In this research, we used tumor and adjacent normal tissue samples from 75 patients diagnosed with breast cancer who had undergone surgery. The levels of gene expression were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study found that ADAR1-p110 expression was significantly higher (1.32-fold, p < 0.0001) in tumor tissue compared to adjacent normal tissue. Similarly, ADAR1-p150 expression also showed a significant increase (1.58-fold, p < 0.0001) in tumor tissue compared to normal tissue. ADAR1-p150 expression was significantly higher in ER (estrogen receptors )-positive patients compared to ER-negative patients (p = 0.04). Additionally, patients with lobular histology showed significantly higher ADAR1-p150 expression levels compared to those with ductal histology (p = 0.02). Our findings, obtained by using tumor and normal tissue from the same individual, demonstrate increased ADAR1 gene expression in tumor tissue. Considering the literature data indicating ADAR1′s association with drug resistance and the correlation we observed between ADAR1 expression levels and certain clinicopathological data of the patients, it is evident that ADAR1 expression is a parameter that should be taken into account in treatment planning.

ADAR1介导的RNA编辑对哺乳动物的生存至关重要，其功能障碍导致其靶标的不规则编辑，可能影响乳腺癌的可观察特征。本研究旨在研究ADAR1- p110和ADAR1-p150基因在乳腺癌患者组织样本（肿瘤和正常）中的表达，确定其在肿瘤发展中的作用，并将表达水平与患者临床表现相关联，以了解乳腺癌的异质性。在这项研究中，我们使用了75名接受过手术的乳腺癌患者的肿瘤和邻近正常组织样本。采用逆转录-定量聚合酶链反应（RT-qPCR）测定基因表达水平。研究发现，ADAR1-p110表达显著增高(1.32倍，p <；0.0001)，肿瘤组织与邻近正常组织相比。同样，ADAR1-p150的表达也显著增加(1.58倍，p <；0.0001)，与正常组织相比。雌激素受体（ER）阳性患者ADAR1-p150表达明显高于ER阴性患者（p = 0.04）。此外，小叶组织学患者的ADAR1-p150表达水平明显高于导管组织学患者（p = 0.02）。我们通过使用来自同一个体的肿瘤组织和正常组织获得的研究结果表明，ADAR1基因在肿瘤组织中的表达增加。结合ADAR1与耐药相关的文献资料，以及我们观察到的ADAR1表达水平与患者某些临床病理数据的相关性，可见ADAR1表达是治疗计划中应考虑的一个参数。

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引用次数: 0

Two MLN-TK patients with ETV::ABL1 fusions mediated by different mechanisms with false negative FISH results resolved with RNA fusion analysis 2例由不同机制介导的ETV::ABL1融合的MLN-TK患者，FISH结果为假阴性，通过RNA融合分析解决

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-06-29 DOI: 10.1016/j.cancergen.2025.06.007

Patrick Maher , Tim Jang , Ruben Ruiz Vega , Jennifer Miatech , Gabriela Bastidas Mora , W.J.R. Quan , Reeba Prince , Joanna Chaffin , Lijun Yang , Petr Starostik , Rachel D. Burnside

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusions (MLN-TK) is a newly added entity in the World Health Organization (WHO) 5^th Edition, and within this category, ETV6::ABL1 gene fusions are the most commonly reported in the literature. While patients may respond favorably to tyrosine kinase inhibitor (TKI) therapy, prognosis is generally less favorable than for BCR::ABL1-positive chronic myelogenous leukemia (CML), also treated with tyrosine kinase inhibitor therapy (TKIs). We report two patients diagnosed with MLN-TK, both of whom were positive for ETV6::ABL1 gene fusions, albeit by different mechanisms but with the same breakpoints. Importantly, one of our subjects also demonstrated BCR::ABL1 fusion subclonally to the ETV6::ABL1 fusion positive clone. This study emphasizes the importance of resolving false negative and/or discrepant fluorescence in situ hybridization (FISH) results using alternative methods, such as RNA fusion analysis, to aid in the diagnosis of MLN-TK.

髓系/淋巴系肿瘤伴嗜酸性粒细胞增多和酪氨酸激酶融合（MLN-TK）是世界卫生组织（WHO）第5版中新增的一个实体，在这一类别中，ETV6::ABL1基因融合是文献中最常报道的。虽然患者可能对酪氨酸激酶抑制剂（TKI）治疗反应良好，但预后通常不如BCR:: abl1阳性的慢性髓性白血病（CML），后者也接受酪氨酸激酶抑制剂治疗（TKIs）。我们报告了两例被诊断为MLN-TK的患者，他们都是ETV6::ABL1基因融合阳性，尽管通过不同的机制，但具有相同的断点。重要的是，我们的一个受试者也展示了BCR::ABL1与ETV6::ABL1融合阳性克隆的亚克隆融合。本研究强调了利用RNA融合分析等替代方法解决假阴性和/或差异荧光原位杂交（FISH）结果的重要性，以帮助诊断MLN-TK。

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