Unlocking Clinical Insights: Lymphocyte-Specific Protein Tyrosine Kinase Candidates as Promising Therapeutic Targets for Pancreatic Cancer Risk Stratification.

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Huan Zhang, Paul Winter, Thomas Wartmann, Luca Simioni, Sara Al-Madhi, Aris Perrakis, Roland S Croner, Wenjie Shi, Quan Yu, Ulf D Kahlert
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Abstract

Background: Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. Methods: This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. Results: After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. LAMA3 turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of LAMA3 had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of LAMA3 turned out to be OPI5-AS1/hsa-miR-186-5p/LAMA3 axis. Conclusions: A characteristic signature of seven Lck-related genes, especially LAMA3, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.

开启临床洞察力:淋巴细胞特异性蛋白酪氨酸激酶候选靶点有望成为胰腺癌风险分层的治疗靶点。
背景:揭示淋巴细胞特异性蛋白酪氨酸激酶(Lck)相关基因与胰腺癌临床风险分层之间的关键联系。方法:本研究以癌症基因组图谱(The Cancer Genome Atlas)数据库为基础,采用一种方法框架来识别胰腺癌中差异表达基因(DEGs)与 Lck 相关基因之间的共享基因。完成特征基因选择并构建特征模型。定义了具有统计学意义的临床终点,如总生存期(OS)、疾病特异性生存期(DSS)和无进展间期(PFI)。结果在进行随机生存森林、Lasso 回归和多变量 Cox 回归模型后,从 272 个 Lck 相关 DEGs 中筛选出 7 个性状基因,创建了一个独立于其他临床因素并能预测 OS 和 DSS 的特征模型。高危患者似乎激活了TP53信号通路和细胞周期信号通路。LAMA3是胰腺癌高表达特征的枢纽基因。相比之下,LAMA3表达增加的患者的OS、DSS和PFI都较短。LAMA3的候选竞争内源性RNA网络是OPI5-AS1/hsa-miR-186-5p/LAMA3轴。结论七个Lck相关基因(尤其是LAMA3)的特征特征已被证明是胰腺癌临床风险分层的关键因素。
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来源期刊
CiteScore
7.80
自引率
2.90%
发文量
87
审稿时长
3 months
期刊介绍: Cancer Biotherapy and Radiopharmaceuticals is the established peer-reviewed journal, with over 25 years of cutting-edge content on innovative therapeutic investigations to ultimately improve cancer management. It is the only journal with the specific focus of cancer biotherapy and is inclusive of monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapies. The Journal includes extensive reporting on advancements in radioimmunotherapy, and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments.
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