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Genetic susceptibility loci of lung cancer are associated with malignant risk of pulmonary nodules and improve malignancy diagnosis based on CEA levels

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Chinese Journal of Cancer Research 2023年第5期35卷 501-510页

作者： Zhi Li Liming Lu Yibin Deng Amei Zhuo Fengling Hu Wanwen Sun Guitian Huang Linyuan Liu Boqi Rao Jiachun Lu Lei Yang The State Key Lab of Respiratory Disease Institute of Public HealthGuangzhou Medical UniversityGuangzhou 511436China Center for Medical Laboratory Science the Affiliated Hospital of Youjiang Medical University for NationalitiesBaise 533000China Physical examination center Guangzhou First People’s HospitalGuangzhou 511468China

Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health *** the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in ***,current understanding of the genetic loci associated with malignant PN(MPN)risk is ***:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)*** genotyped 11 established susceptibility loci for lung cancer in a Chinese *** associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor ***:loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of *** PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS *** bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait ***:loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.

关键词： Pulmonary nodules susceptible loci serum tumor biomarkers polygenic risk score diagnosis

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A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer

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Chinese Journal of Cancer Research 2023年第5期35卷 511-525页

作者： Jing Zhang Haohua Yao Chunliu Lai Xue Sun Xiujuan Yang Shurong Li Yubiao Guo Junhang Luo Zhihua Wen Kejing Tang Division of Pulmonary and Critical Care Medicine the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Urology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Respiratory and Critical Care Medicine the Fourth People’s Hospital of ShenyangShenyang 110031China Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Department of Radiology the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Urology the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Pharmacy the First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China

Objective:DNA methylation alterations are early events in carcinogenesis and immune signalling in lung *** study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4gene (PTGER4) DNA methylation in plasma,appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung ***:We developed a multimodal prediction model with a training set of 257 *** performance of the multimodal prediction model was further validated in an independent validation set of 42 *** addition,we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) ***:There were significant differences between the early-stage lung cancers and benign groups in the methylation *** area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules,mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693,0.497 and 0.864,respectively,while the AUCs of PTGER4 were 0.559,0.739 and 0.619,*** the highest AUC of0.894,the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation *** analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 ***:The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs.A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

关键词： Pulmonary nodules susceptible loci serum tumor biomarkers polygenic risk score diagnosis

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