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分析表达在胰腺腺癌中的作用:了解预后意义和治疗机会。

Analyzing the role of expression in pancreatic adenocarcinoma: understanding prognostic implications and therapeutic opportunities.

作者信息

Xu Dong, Jia Mingguang, Yang Fei, Zhang Xiaohui, Jiang Kuirong

机构信息

Pancreas Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of General Surgery, Gaochun People's Hospital, Nanjing, China.

出版信息

J Gastrointest Oncol. 2024 Aug 31;15(4):1760-1776. doi: 10.21037/jgo-24-564. Epub 2024 Aug 28.

Abstract

BACKGROUND

Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by aggressive growth and poor prognosis. Understanding the molecular mechanisms underlying PAAD is crucial for developing effective therapies. This study aimed to explore the role of and other key genes in PAAD progression, their prognostic implications, and therapeutic opportunities.

METHODS

Differential gene expression analysis was performed using PAAD and normal tissue samples to identify upregulated genes, with emerging as significantly elevated in PAAD. Functional enrichment analysis elucidated associated signaling pathways. A prognostic model comprising , , and was developed using least absolute shrinkage and selection operator (LASSO) regression and validated in an independent cohort. Genetic mutation analysis provided insights into the functional significance of identified genes. Pharmacogenomic analysis examined associations between gene expression and drug sensitivity. Experimental validation included quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses to confirm gene expression patterns and protein levels.

RESULTS

Lower expression correlated with enhanced anti-tumor immune activity in PAAD, suggesting a complex interplay between genetic expression and immune response. The prognostic model showed robust associations with patient survival outcomes, validated across diverse patient cohorts. Genetic mutation analysis highlighted potential therapeutic targets. Pharmacogenomic analysis revealed correlations between gene expression profiles and drug responsiveness, suggesting personalized treatment strategies. Experimental validation confirmed elevated levels in tumor tissues and demonstrated its role in promoting cancer cell proliferation and colony formation.

CONCLUSIONS

This study advances understanding of the molecular landscape of PAAD, emphasizing as a key regulator and potential therapeutic target. The integration of genetic expression, immune response dynamics, and pharmacogenomics offers a multifaceted approach to personalized treatment strategies for PAAD, paving the way for improved patient outcomes and novel therapeutic interventions. Further research is warranted to elucidate the clinical utility of targeting and other identified genes in PAAD management.

摘要

背景

胰腺腺癌(PAAD)是一种高度致命的恶性肿瘤,其特征为生长侵袭性强且预后不良。了解PAAD潜在的分子机制对于开发有效的治疗方法至关重要。本研究旨在探讨[具体基因名称]及其他关键基因在PAAD进展中的作用、它们的预后意义以及治疗机会。

方法

使用PAAD和正常组织样本进行差异基因表达分析以鉴定上调基因,[具体基因名称]在PAAD中显著升高。功能富集分析阐明了相关信号通路。使用最小绝对收缩和选择算子(LASSO)回归开发了一个包含[具体基因名称]、[具体基因名称]和[具体基因名称]的预后模型,并在独立队列中进行了验证。基因突变分析深入了解了已鉴定基因的功能意义。药物基因组学分析研究了基因表达与药物敏感性之间的关联。实验验证包括定量逆转录聚合酶链反应(qRT-PCR)和蛋白质印迹分析,以确认基因表达模式和蛋白质水平。

结果

较低的[具体基因名称]表达与PAAD中增强的抗肿瘤免疫活性相关,表明基因表达与免疫反应之间存在复杂的相互作用。预后模型与患者生存结果显示出强烈关联,在不同患者队列中均得到验证。基因突变分析突出了潜在的治疗靶点。药物基因组学分析揭示了基因表达谱与药物反应性之间的相关性,提示个性化治疗策略。实验验证证实肿瘤组织中[具体基因名称]水平升高,并证明其在促进癌细胞增殖和集落形成中的作用。

结论

本研究推进了对PAAD分子格局的理解,强调[具体基因名称]作为关键调节因子和潜在治疗靶点的作用。基因表达、免疫反应动态和药物基因组学的整合为PAAD的个性化治疗策略提供了多方面的方法,为改善患者预后和新型治疗干预铺平了道路。有必要进一步研究以阐明靶向[具体基因名称]和其他已鉴定基因在PAAD管理中的临床效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e130/11399867/5d2f4f61711b/jgo-15-04-1760-f1.jpg

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