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

Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While 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 diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci 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 biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The 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 categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.

Effect of EME1 exon variant Ile350Thr on risk and early onset of breast cancer in southern Chinese women

Essential meiotic endonuclease 1 homolog 1 （EME1） is a key DNA repair protein that participates in the rec- ognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME! （i.e.,Ile350Thr： rs12450550T 〉 C and Glu69Asp： rs3760413T 〉 G） and breast cancer risk. We found that compared to the common lie/lie genotype, the Thr variant genotypes （Thr/lle ＋ Thr/Thr） conferred a 1.47-fold increased risk of breast cancer （OR=1.47, 95% CI=I. 13-1.92）. The variant Ile350Thr was also associated with early onset of breast cancer （r = -0.116, P = 0.002）. The mean age of onset was 44.4 years for Thr/Thr genotype carders and 46.5 years for Thr/lle genotype carriers, which was significantly lower than that （49.4 years） for Ile/Ile genotype carriers （P = 0.006）. Moreover, no significant as- sociation was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.

Association of neuregulin-1 with schizophrenia

BACKGROUND： Recent studies have paid much attention to the newly found neuregulin-1, which might be closely linked to the molecular genetics of schizophrenia. OBJECTIVE： To investigate the association of neuregulin-related genes with schizophrenia, and to summarize the advancements in this current research. RETRIEVAL STRATEGY： Using the terms ＂neuregulins, gene, schizophrenia＂, we retrieved articles published from January 2000 to June 2007 from http：//www.ncbi.nlm.gov, http：//www.elsevier.lib.tsinghua.edu.cn, and http：//www.cjfd.cnki.net to identify studies addressing the association of neuregulin-related genes to schizophrenia. At the same time, we searched more than 10 medical journals by hand. The languages were limited to English and Chinese. Forty-two manuscripts were obtained and were firstly screened. Inclusion criteria： studies on neuregulins, schizophrenia, neuregulin-1, and the pathogenesis of schizophrenia, including randomized, blinded, and other original studies. Exclusion criteria： studies not related to schizophrenia, or repetitive studies. LITERATURE EVALUATION： The included 42 manuscripts were sorted. Twenty-one were selected as references for this article： fourteen were basic studies, and the remaining articles were case-controlled studies or other. DATA SYNTHESIS： Neuregulins are primarily expressed in the nervous system and heart, and limited expression is also seen in other tissues.. These proteins transmit signals among certain cells and play an important role in normal development of the nervous system. Neuregulin-1 is a typical neuregulin-related gene. Neuregulin genes are closely related to glutamatergic, GABAergic, and dopaminergic neurons. CONCLUSION： Neuregulin-related genes, such as neuregulin-1, are important and promising candidate genes for studying schizophrenia disease. Their roles in the onset of schizophrenia, neuregulin-related gene expression products, and correlations of ErbB receptor to schizophrenia symptoms need to be further investigated. Further studies of neuregulin-1 will hopefully provide powerful evidence for understanding the pathogenesis of schizophrenia.

Identification of a 10-pseudogenes signature as a novel prognosis biomarker for ovarian cancer

The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted.The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator(LASSO)method.A risk score model based on the prognostic pseudogenes was also constructed.The pseudogene-mRNA regulatory networks were established using correlation analysis,and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis.Lastly,ssGSEA and ESTIMATE algorithms was used to evaluate the levels of immune cell infiltrations in cancer tissues and explore their relationship with risk signature.A prediction model of 10-pseudogenes including RPL10P6,AC026688.1,FAR2P4,AL391840.2,AC068647.2,FAM35BP,GBP1P1,ARL4AP5,RPS3AP2,and AMD1P1 was established.The 10-pseudogenes signature was demonstrated to be an independent prognostic factor in patient with ovarian cancer in the random set(hazard ratio[HR]=2.512,95%confidence interval[CI]=2.03–3.11,P<0.001)and total set(HR=1.71,95%CI=1.472–1.988,P<0.001).When models integrating with age,grade,stage,and risk signature,the Area Under Curve(AUC)of the 1-year,3-year,5-year and 10-year Receiver Operating Characteristic curve in the random set and total set were 0.854,0.824,0.855,0.805 and 0.679,0.697,0.739,0.790,respectively.The results of functional enrichment analysis indicated that the underlying mechanisms by which these pseudogenes influence cancer prognosis may involve the immune-related biological processes and signaling pathways.Correlation analysis showed that risk signature was significantly correlated with immune cell infiltration and immune score.We identified a novel 10-pseudogenes signature to predict the survival of patients with ovarian cancer,and that may serve as novel possible prognostic biomarkers and therapeutic targets for ovarian cancer.

CMGene：A literature-based database and knowledge resource for cancer metastasis genes

Cancer metastasis is the end product of cancer evolution,contributing to the massive mortality of cancer patients（Chaffer and Weinberg,2011）.Different primary cancers have distinct spreading routes via the blood or the lymphatics or through both routes,which presents challenge for effective cancer treatment（Qian et aL,2017）.