1.Relationship between gene mutations and clinicopathological characteristics in patients with non-small cell lung cancer based on high-throughput sequencing
Xueqi YANG ; Zhenwu DU ; Bohong LIU ; Qisheng PANG ; Xuyuan QIN ; Guizhen ZHANG
International Journal of Laboratory Medicine 2025;46(21):2613-2620
Objective To explore the detection rate and distribution characteristics of gene mutations in pa-tients with non-small cell lung cancer,and to analyze their relationship with clinicopathological characteristics.Methods The genetic testing results and clinicopathological data of 213 patients with non-small cell lung cancer who underwent high-throughput genetic testing at the Gene Detection Center,Changchun Cancer Hos-pital from April 2020 to December 2023 were collected.High-throughput sequencing technology was used to detect mutations in 26 genes,and the relationship between the mutation frequency and its distribution and the clinicopathological characteristics of patients was analyzed.Results Among 213 patients with non-small cell lung cancer,192 cases(90.14%)had at least one gene mutation detected.Among them,the genes with rela-tively high mutation frequencies were TP53(60.56%),EGFR(46.48%),KRAS(14.55%),ALK fusion(11.74%),and PIK3CA(8.92%).There were 132 cases(30.28%)of evidence level for Class 1 drugs and 11 cases(2.52%)of evidence level for Class 2 drugs.The incidence of EGFR gene mutations was higher in women,non-smokers and patients with lung adenocarcinoma(P<0.05).TP53 mutations usually occured in women,smokers and patients with stage Ⅳ.ALK mutations were more common in young patients,while KRAS mutations were more frequently seen in male smokers.Conclusion Analyzing the distribution charac-teristics of gene mutations in non-small cell lung cancer and their relationship with clinicopathological charac-teristics can provide a scientific basis for further optimizing genetic testing for patients with non-small cell lung cancer and offer guidance for clinical treatment.
2.Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.
Yongchun PAN ; Xiaowei LUAN ; Fei ZENG ; Xuyuan WANG ; Shurong QIN ; Qianglan LU ; Guanzhong HE ; Yanfeng GAO ; Xiaolian SUN ; Xin HAN ; Bangshun HE ; Yujun SONG
Acta Pharmaceutica Sinica B 2024;14(2):795-807
Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

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