The impact of Radioresistant-Related Telomere Genes in the prognosis and immune infiltration in lung adenocarcinoma.

IF 5.3 2区 医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-11-23 DOI:10.1186/s12935-024-03564-2
Peng Li, Lu Meng, Hongbin Tu, Shilan Luo, Xiaomei Gong
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Abstract

Introduction: Lung adenocarcinoma (LUAD), a common subtype of NSCLC, has a high mortality rate. Telomere genes are influenced by radiation therapy, affecting treatment response. Additionally, immune cell presence in the tumor microenvironment plays a crucial role in cancer prognosis. However, the role of Radioresistant-Related Telomere Genes (RRTGs) in LUAD prognosis and immune infiltration remains unclear.

Methods: In this research, we utilized diverse bioinformatics techniques to examine our personally tested information along with publicly accessible datasets. We conducted a comprehensive study on the genetic and transcriptional differences, predictive significance, and expression profiles of RRTGs. Afterwards, a RRTGs score was developed to forecast the overall survival (OS) and ascertain its reliable predictive capacity for patients with LUAD. Following this, dependable nomograms were developed to enhance the practicality of RRTGs scoring in a clinical setting. Furthermore, the investigation delved into the associations among RRTGs, infiltration of immune cells, prognosis, and clinical treatments of patients. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential mechanisms by which RRTGs influence the regulation of LUAD. Then, Western blot, qRT-PCR and Immunohistochemistry were used to detect the expression levels of RRTGs in cell lines and LUAD tumor tissues.

Results: Our research indicates that certain genes related to telomeres have a notable correlation with the prognosis of patients diagnosed with LUAD. The RRTGs score, which includes three key genes (ARRB1, PLK1, and DSG2), was developed to forecast the OS and its dependable predictive capability for individuals diagnosed with LUAD was ascertained. Afterwards, extremely reliable nomograms were developed to improve the practicality of the RRTGs score. Moreover, as illustrated, genetic characteristics can be utilized to assess the infiltration of immune cells in tumors, as well as clinical attributes and prognosis. RRTGs score characterizes tumor mutational burden, immune activity, and notable survival probabilities in addition. Furthermore, GSEA results revealed that RRTGs may influence LUAD by modulating immune-related pathways in high-risk groups and regulating cell cycle and DNA repair processes in low-risk groups. The RRTGs (ARRB1 and PLK1) were upregulated in A549 cells and radiosensitive NSCLC tissues compared to radioresistant A549 cells and NSCLC tissues.

Conclusion: In conclusion, this research emphasizes the significance of RRTGs in the outlook of LUAD. The findings contributed to a better understanding of the link between radiotherapy, telomere-related genes, and prognosis in LUAD, and identified potential therapeutic targets for patients with LUAD.

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放射性抗原相关端粒基因对肺腺癌预后和免疫浸润的影响
简介肺腺癌(LUAD)是一种常见的 NSCLC 亚型,死亡率很高。端粒基因会受到放射治疗的影响,从而影响治疗反应。此外,肿瘤微环境中免疫细胞的存在对癌症预后也起着至关重要的作用。然而,放射性抗性相关端粒基因(RRTGs)在LUAD预后和免疫浸润中的作用仍不清楚:在这项研究中,我们采用了多种生物信息学技术,对我们亲测的信息和可公开获取的数据集进行了检验。我们对 RRTGs 的遗传和转录差异、预测意义和表达谱进行了全面研究。随后,我们开发了 RRTGs 评分来预测 LUAD 患者的总生存率(OS),并确定其可靠的预测能力。随后,研究人员还开发了可靠的提名图,以提高 RRTGs 评分在临床环境中的实用性。此外,研究还深入探讨了RRTGs、免疫细胞浸润、预后和患者临床治疗之间的关联。基因组富集分析(Gene Set Enrichment Analysis,GSEA)探讨了RRTGs影响LUAD调控的潜在机制。然后,采用Western blot、qRT-PCR和免疫组化等方法检测RRTGs在细胞系和LUAD肿瘤组织中的表达水平:结果:我们的研究表明,某些与端粒相关的基因与LUAD患者的预后有显著的相关性。我们开发了包括三个关键基因(ARRB1、PLK1 和 DSG2)的 RRTGs 评分来预测 OS,并确定了其对确诊的 LUAD 患者的可靠预测能力。随后,又开发了极为可靠的提名图,以提高 RRTGs 评分的实用性。此外,如图所示,遗传特征可用于评估肿瘤中免疫细胞的浸润情况以及临床属性和预后。RRTGs 评分还能描述肿瘤突变负荷、免疫活性和显著的生存概率。此外,GSEA结果显示,RRTGs可能通过调节高风险组的免疫相关通路和调节低风险组的细胞周期和DNA修复过程来影响LUAD。与抗放射的A549细胞和NSCLC组织相比,RRTGs(ARRB1和PLK1)在A549细胞和放射敏感的NSCLC组织中上调:总之,这项研究强调了RRTGs在LUAD前景中的重要性。研究结果有助于更好地理解放疗、端粒相关基因和LUAD预后之间的联系,并为LUAD患者确定了潜在的治疗靶点。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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