A demonstration based on multi-omics transcriptome sequencing data revealed disulfidptosis heterogeneity within the tumor microenvironment of esophageal squamous cell carcinoma.

BACKGROUND: It is of great concern to identify prognostic signatures for the prediction and prediction of esophageal squamous cell carcinoma (ESCC), which is the lethal pathological type of malignancy. METHOD: Bulk RNA sequencing and scRNA-seq data were retrieved from GSE53624, GSE53622, and GSE188900. Disulfidptosis-related differentially expressed genes (DEGs) were identified between disulfidptosis-high score and disulfidptosis-low score groups. Functional annotation of DEGs were analyzed by Gene Ontology (GO). Consistent clustering and co-expression modules were analyzed, and then constructed a risk score model via multivariate Cox regression analysis. Immune infiltration and immunotherapy response analyses were conducted based on risk score. qRT-PCR, colony formation assay, and flow cytometry analysis were conducted in KYSE-150 and TE-1 cell lines. RESULTS: Seven genes (CD96, CXCL13, IL2RG, LY96, TPK1, ACAP1, and SOX17) were selected as marker genes. CD96 and SOX17 are independent prognostic signatures for ESCC patients, with a significant correlation with infiltrated immune cells. ESCC patients had worse response to nivolumab in the high-risk group. Through cellular experiments, we found that CD96 expression was associated with apoptosis and cell cycle ESCC cells. CONCLUSION: In a word, the risk score based on disulfidptosis is associated with prognosis and the immune microenvironment, which may direct immunotherapy of ESCC. The key gene of risk score, namely CD96, plays a role in proliferation and apoptosis in ESCC. We offer an insight into the exploration of the genomic etiology of ESCC for its clinical management.

Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Background: Inflammation is not only involved in the development and progression of cancer but also affects the response to therapy. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in inflammation genes with the prognosis of advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Methods: Forty-seven SNPs were genotyped in 318 advanced NSCLC patients receiving EGFR-TKIs. Of 318 patients, 182 (57.2%) patients died during follow-up period. We assessed the association of SNPs with the progression-free survival (PFS) and overall survival (OS) as well as calculated the weighted genetic risk score (GRS). We also explored the expression levels and prognostic values of inflammation genes in lung adenocarcinoma (LUAD) in Gene Expression Profiling Interactive Analysis (GEPIA) and using UCSC Xena, respectively. The relationship between the expression levels of IL15, IL17RA, AGER, MIF, and TNFRSF1A and EGFR mutation status was analyzed using UCSC Xena. Results: In single variant analyses, 3 SNPs (rs10519613, rs4819554, and rs4149570) were significantly associated with worse PFS. Five SNPs (rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) were significantly with worse OS. In addition, high and intermediate GRSs (based on rs10519613, rs4819554, and rs4149570) were associated with worse PFS than those with low GRS. For OS, patients with high GRSs (based on rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) had shorter survival time than those with low GRS. Furthermore, IL15, IL17RA, AGER, MIF, and TNFRSF1A were dysregulated in LUAD. There was difference in the expression level of TNFRSF1A between EGFR wildtype and EGFR-mutant LUAD. Both low AGER expression and high TNFRSF1A expression were significantly associated with worse PFS in LUAD. In addition, low IL17RA and AGER expression, high MIF and TNFRSF1A expression were significantly associated with worse OS in LUAD. Conclusion: SNPs in inflammation genes could serve as prognostic biomarkers for NSCLC patients treated with EGFR-TKIs.

MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death in China. Dysregulation of microRNAs (miRNAs) is involved in cancer development and progression. Our previous study showed an inverse relationship between miR-193a-3p expression and the prognosis of CRC. However, the exact biological functions of miR-193a-3p in CRC are still poorly understood. This study aimed to explore the role and mechanism of miR-193a-3p in CRC. METHODS: Real-time PCR and Western blotting were used to examine the expression levels of RNA and protein, respectively. A dual luciferase assay was performed to validate predicted targets of miR-193a-3p. Loss and gain-of-function studies were carried out to reveal the effects and potential mechanism of the miR-193a-3p in the proliferation, metastasis and angiogenesis of CRC cells. RESULTS: The expression levels of miR-193a-3p in human CRC cell lines were significantly decreased compared with that in normal colonic epithelium cell line. Furthermore, plasminogen activator urokinase (PLAU) was validated as a direct target gene of miR-193a-3p. Over-expression of miR-193a-3p inhibited proliferation, migration and angiogenesis of HT-29 cell, whereas forced expression of PLAU could rescue the inhibitory effects. CONCLUSION: miR-193a-3p might inhibit CRC cell growth, migration and angiogenesis partly through targeting PLAU. MiR-193a-3p/PLAU axis might provide a potent therapeutic opportunity for aggressive CRC.

The Relationship Between ZEB1-AS1 Expression and the Prognosis of Patients With Advanced Gastric Cancer Receiving Chemotherapy.

Long noncoding RNA ZEB1 antisense RNA 1 plays a vital role in tumorigenesis and metastasis. However, the role of ZEB1 antisense RNA 1 in gastric cancer remains unclear. This study aimed to investigate the expression level of ZEB1 antisense RNA 1 in gastric cancer tissues and evaluate its association with clinicopathological features and prognosis of patients with advanced gastric cancer receiving chemotherapy. The expression levels of ZEB1 antisense RNA 1 were examined in 224 pairs of gastric cancer and adjacent noncancerous tissues by quantitative real-time polymerase chain reaction. The associations between ZEB1 antisense RNA 1 expression and clinicopathological features or survival of patients with advanced gastric cancer were assessed. The results showed that the expression levels of ZEB1 antisense RNA 1 in gastric cancer tissues were significantly higher than those in the paracancerous tissues ( P < .001). Moreover, the high ZEB1 antisense RNA 1 expression was associated with tumor, nodes, and metastases stage IV ( P = .018) and loss of E-cadherin expression ( P = .033). Multivariate Cox hazards regression analysis revealed that high ZEB1 antisense RNA 1 expression was an independent risk factor for predicting poor prognosis in patients with advanced gastric cancer (hazard ratio = 1.530, 95% confidence interval, 1.052-2.224, P = .026). In conclusion, the present findings suggest that ZEB1 antisense RNA 1 is an independent prognostic factor for patients with advanced gastric cancer receiving chemotherapy.

Detection of the clarithromycin resistance of Helicobacter pylori in gastric mucosa by the amplification refractory mutation system combined with quantitative real-time PCR.

The goal of this study was to evaluate the feasibility of detecting Helicobacter pylori clarithromycin resistance in gastric mucosa using the amplification refractory mutation system combined with quantitative real-time PCR (ARMS-PCR). Gastric mucosal specimens (150) were collected from patients who were unsuccessfully treated for H. pylori eradication. Each specimen was divided into 2 samples. One sample was used to extract genomic DNA and detect any gene mutations of H. pylori produced by ARMS- PCR. Sequencing was used to assess the accuracy of this method. The other sample was used to culture H. pylori. The E-test minimum inhibitory concentration (MIC) was used to assess clarithromycin resistance. The results were compared with a paired chi-square test to validate the coincidence rate among the 3 methods. The coincidence rate between the sequencing and ARMS-PCR results was 98.7%, thus verifying the accuracy of ARMS-PCR. E-tests detected 144 clarithromycin resistance cases, including 45 sensitivity cases; the resistance rate was 70%. The coincidence rate between the results of the E-test and ARMS-PCR was 97.1%, and no significant difference between the 2 methods was observed. ARMS-PCR is a simple and fast method that has high sensitivity and specificity and can be used to detect the clarithromycin resistance of H. pylori in gastric mucosa. ARMS-PCR is expected to be used to study drug resistance mechanisms and use in assays of individual therapies for H. pylori eradication.

Increased expression of plakophilin 3 is associated with poor prognosis in ovarian cancer.

Considering the essential role of plakophilin 3 (PKP3) in the maintenance cell-cell adhesion, dysregulation of PKP3 is involved in human diseases. This study aimed to explore the clinical significance of PKP3 in ovarian cancer. Immunohistochemistry was performed to examine the PKP3 expression in 157 cancer specimens from primary ovarian cancer patients. PKP3 was expressed in both the cytoplasm and nucleus. Eighty-one (51.6%) out of 157 ovarian cancer tissues showed PKP3 expression, while absent expression was observed in normal ovarian tissues. High PKP3 expression was associated with lymph node metastasis (LNM, P = .004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = .013). Patients with high PKP3 expression had shorter overall survival (OS) than those with low PKP3 expression (60.2 months vs 74.2 months, P = .021). However, no association between PKP3 expression and progression-free survival (PFS) was observed (P = .790). Cox regression analysis indicated that PKP3 expression was an independently predictive factor for the OS of patient with ovarian cancer (adjusted HR = 1.601, 95%CI: 1.014-2.528, P = .043), especially those with FIGO stages III and IV disease (adjusted HR = 1.607, 95%CI: 1.006-2.567, P = .047). The gene expression profiling interactive analysis (GEPIA) databases also showed that PKP3 was upregulated in ovarian cancer (P < .001) and patients with high PKP3 expression had shorter OS (P = .004). In conclusion, our findings suggest that PKP3 is upregulated in ovarian cancer and is likely involved in the progression of ovarian cancer. PKP3 might therefore serve as a prognostic biomarker for patients with ovarian cancer.

Retinoblastoma Binding Protein 5 Correlates with the Progression in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancy tumors with insidious onset, rapid development and metastasis, and poor prognosis. Therefore, it is necessary to understand molecular mechanisms of HCC and identify clinically useful biomarkers for it. This study aimed to investigate the role of retinoblastoma binding protein 5 (RBBP5) in HCC. The expression level of RBBP5 was examined by immunohistochemistry and western blot. The effect of RBBP5 on cell cycle, proliferation, apoptosis, and drug sensitivity was analyzed. RBBP5 was significantly upregulated in HCC tissues and cells. High RBBP5 expression was significantly associated with elevated level of AFP, advanced TNM stage, high Ki-67 expression, larger tumor size, and poor prognosis. Knockdown of RBBP5 significantly inhibited proliferation of HCC cells through cell cycle arrest. In addition, inhibition of RBBP5 increased the sensitivity of HCC cells to doxorubicin. In conclusion, our findings suggest that RBBP5 plays an important role in the progression of HCC and may serve as a novel biomarker and potential therapeutic target for HCC.

Mediating Effect of Diabetes Mellitus on the Association Between Chromosome 9p21.3 Locus and Myocardial Infarction Risk: A Case-Control Study in Shanghai, China.

Background: Previous genome-wide association studies revealed that the chromosome 9p21.3 locus is associated with an increased risk of myocardial infarction (MI) and diabetes mellitus (DM). However, it is unclear whether the 9p21.3-MI association is direct or mediated by pathways related to DM. Study Design: We applied mediation analysis to examine the potential mediating effect of DM on the association between the 9p21.3 genetic risk score (GRS; ranged from 0 to 8) and MI in a case-control study of 865 MI patients and 927 controls without coronary artery disease (CAD). The GRS combining 4 lead 9p21.3 single nucleotide polymorphisms (rs1333040, rs4987574, rs2383207, and rs1333049) was constructed. Results: Each 1 unit increase in weighted 9p21.3 GRS was associated with a 9% increased DM risk (95% confidence interval (CI) 1.00, 1.19) in the control group and a 14% increased MI risk (95% CI 1.09, 1.20). Mediation analyses yielded a direct-effect odds ratio (OR) of 1.06 (95% CI 1.04, 1.08) and an indirect-effect OR of 1.00 (95% CI 0.99, 1.01) for weighted GRS. DM mediated 4.40% (95% CI 3.42, 6.52) of the total association between the weighted GRS and MI risk. Individuals with the highest quartile of 9p21.3 GRS and DM had a 6-fold higher MI risk than those with the lowest quartile of 9p21.3 GRS and non-DM (OR 6.03, 95% CI 3.48, 10.5). Conclusion: DM is a weak mediator that explains a small fraction of the 9p21. 3-MI association in Chinese adults. Nevertheless, there is a strong synergistic effect between DM and the 9p21.3 GRS on MI risk.

Clinical significance of ubiquilin 1 in gastric cancer.

Ubiquilin 1 (UBQLN1) plays an essential role in the regulation of protein degradations which is involved in the pathophysiology of neurodegenerative diseases and cancer. This study aimed to investigate the expression level of UBQLN1 in gastric cancer and evaluated the relationship between its expression and clinicopathological characteristics, as well as prognostic of patients with gastric cancer. Immunohistochemistry (IHC) was used to detect the expression levels of UBQLN1 in 179 pairs of gastric cancer and adjacent normal tissues. The UBQLN1 was significantly upregulated in gastric cancer tissue. High UBQLN1 expression was associated with high histological grade, invasion, lymph node metastasis, and tumor node metastasis (TNM) stage III (P < .001). Multivariate Cox analysis showed that larger tumor size (HR = 3.125, 95%CI: 2.031-4.808, P < .001), histological grade 3 (HR = 15.313, 95%,CI: 8.075-29.041, P < .001), pT3 + pT4 (HR = 3.224, 95%CI: 1.389-7.483, P = .006), LNM (HR = 4.467, 95%CI: 2.404-8.302, P < .001), TNM stage III (HR = 2.152, 95%CI: 1.289-3.594, P = .003), and high UBQLN1 expression (HR = 2.547, 95%CI: 1.511-4.292, P < .001) were significantly associated with worse prognosis of patients with gastric cancer. In conclusion, high UBQLN1 expression was an independent worse prognostic factor for patients with gastric cancer.

Conditional Inference Tree for Multiple Gene-Environment Interactions on Myocardial Infarction.

BACKGROUND AND AIMS: Identifying gene-environment interaction in the context of multiple environmental factors has been a challenging task. We aimed to use conditional inference tree (CTREE) to strata myocardial infarction (MI) risk synthesizing information from both genetic and environmental factors. METHODS: We conducted a case-control study including 1440 Chinese men (730 MI patients and 710 controls). We first calculated a weighted genetic risk score (GRS) by combining 25 single nucleotide polymorphisms (SNPs) that had been identified to be associated with coronary artery diseases in previous genome wide association studies. We then developed a CTREE model to interpret the gene-environment interaction network in predicting MI. RESULTS: We detected high-order interactions between dyslipidemia, GRS, smoking status, age and diabetes. Of all the variables examined, high density lipoprotein cholesterol (HDL-C) of 1.25 mmlo/L was identified as the key discriminator. The subsequent splits of MI were low density lipoprotein cholesterol (LDL-C) of 4.01 mmol/L and GRS of 20.9. We found that individuals with HDL-C ≤1.25 mmol/L, GRS >20.9 and lipoprotein (a) > 0.09 g/L had a higher risk of MI than those who at the lowest risk group (OR: 5.89, 95% CI: 3.99-8.69). This magnitude of MI risk was similar to the combination of HDL-C ≤1.25 mmol/L, GRS ≤20.9, smoking and lipoprotein (a) > 0.15 g/L (OR: 5.49, 95% CI: 3.51-8.58). CONCLUSIONS: The multiple interactions between genetic and environmental factors can be visually present via the CTREE approach. The tree diagram also simplifies the decision making procedure by answering a sequence of questions along the branches.

Decreased expression of miR-193a-3p is associated with poor prognosis in colorectal cancer.

Epithelial-mesenchymal transition (EMT) is an early and key process in the metastatic cascade during the progression of colorectal cancer (CRC). The aim of the present study was to identify deregulated EMT-related microRNAs (miRNAs/miRs) of CRC and assess the effect of differentially expressed miRNAs on the prognosis of patients with CRC. Genome-wide expression profiling of miRNAs was assessed in 3 EMT-negative and 3 EMT-positive CRC tissues. Differentially expressed miRNA was further validated in 90 pairs of CRC and corresponding paracarcinoma tissues using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 6 miRNAs (miR-10a-5p miR-204-3p, miR-1224-3p, miR-193a-3p, miR-365a-3p and miR-3678-3p) were identified to be differentially expressed between different EMT statuses of CRC tissues. Following validation using RT-qPCR, 3 miRNAs (miR-10a-5p, miR-365a-3p and miR-193a-3p) were selected for subsequent studies. The expression levels of miR-10a-5p, miR-193a-3p and miR-365a-3p were markedly increased compared with levels in corresponding paracarcinoma tissues. Survival analyses revealed that down-regulation of miR-193a-3p was associated with worse prognosis of patients with CRC, particularly in female and older patients. The results of the present study indicate that miR-193a-3p may be an EMT-related biomarker and serve as a novel prognostic factor for CRC.

Utility of genetic variants to predict prognosis in coronary artery disease patients receiving statin treatment.

Statins are widely used drugs for lowering low-density lipoprotein cholesterol (LDL-C) and can prevent cardiovascular events. This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) and their cumulative effects on the prognosis of coronary artery disease (CAD) patients treated with statins. Sixteen SNPs were genotyped in 785 CAD patients receiving statin therapy, and their associations with clinical features and prognosis of patients were investigated. Four SNPs (rs2296651, rs11206510, rs8192870, and rs1801133) were significantly associated with complications of CAD (P<0.05). Four SNPs (rs8192870, rs4149056, rs12916, and rs2231142) affected blood lipid levels (P<0.05). Furthermore, rs1801133 showed a weak but significant association with fasting plasma glucose (P = 0.033). Survival analyses showed that rs11206510 (adjusted HR = 1.891, 95% CI: 1.188-3.010, P = 0.007) and rs1801133 (adjusted HR = 1.499, 95% CI: 1.141-1.971, P = 0.004) were independently associated with an increased risk of major cardiovascular events, and exhibited cumulative effect on even-free survival (adjusted HR = 1.810, 95% CI: 1.179-2.802, P = 0.007). In conclusion, rs11206510 and rs1801133 were independent risk factors for clinical outcome in CAD patients treated with statins.

Intravascular NK/T-cell lymphoma in the testis: a novel case report and review of the literature.

Intravascular NK/T-cell lymphoma (IVNKTL) is an extremely rare type of lymphoma that frequently affects the skin. To date, only 14 cases of IVNKTL have been described. To the best of our knowledge, this is the first case report of IVNKTL in the testis.

High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

PURPOSE: Long noncoding RNAs (lncRNAs) play critical roles in diverse biological processes such as tumorigenesis and metastasis. Taurine upregulated gene 1 (TUG1) is a cancer-related lncRNA that is associated with chromatin-modifying complexes and plays an important role in gene regulation. In this study, we determined the expression patterns of TUG1 in esophageal squamous cell carcinoma (ESCC) and evaluated its clinical significance. METHODS: The expression level of TUG1 was examined in 218 pairs of ESCC and adjacent non-cancerous tissues by using quantitative real-time polymerase chain reaction. The relationship between TUG1 expression and clinical features and prognosis was statistically analyzed. RESULTS: The expression level of TUG1 was significantly upregulated in ESCC tissues compared with paired adjacent normal tissues. High TUG1 expression was significantly correlated with chemotherapy resistance. Survival analysis showed that patients with high TUG1 expression had poor prognosis, especially for cases with well and moderate differentiation, ulcerative type, smaller size, and chemotherapy-sensitive tumors. CONCLUSIONS: Our findings suggest that elevated TUG1 expression is related to chemotherapy resistance and may help predict a poor prognostic outcome of ESCC. TUG1 may provide a potential therapeutic target for ESCC.

UCA1 overexpression predicts clinical outcome of patients with ovarian cancer receiving adjuvant chemotherapy.

PURPOSE: Urothelial carcinoma associated 1 (UCA1) functions as an oncogene, which promotes cancer cell proliferation, invasion, and metastasis, and is responsible for drug resistance. This study aimed to determine the expression level of UCA1 in ovarian cancer and to further investigate its clinical significance. METHODS: The expression levels of UCA1 in ovarian cancer and normal ovaries were determined by quantitative real-time PCR. The relationship between UCA1 expression and clinical features and the prognostic value of UCA1 for overall survival were examined. RESULTS: UCA1 expression in ovarian cancer tissues was significantly upregulated compared with normal ovarian tissues. High UCA1 expression was related to lymph node metastasis, FIGO stage, and response to chemotherapy. Kaplan-Meier analysis demonstrated that high UCA1 expression was associated with poorer overall survival in patients with ovarian cancer. Cox proportional hazards analysis showed that high UCA1 expression was an independent prognostic marker of poor outcome. This effect remained significant in the further stratification analysis. CONCLUSIONS: Our findings provided the first evidence that UCA1 may serve as an indicator of response to chemotherapy and prognosis of ovarian cancer. UCA1 may play an important role in the progression of ovarian cancer.

Long non-coding RNA expression profile in atrial fibrillation.

To investigate the expression profiles of long non-coding RNAs (lncRNAs) in atrial fibrillation (AF), atrial tissues from 3 AF patients and 3 non-AF patients that were collected for lncRNA expression microarray analyses to explore the role of lncRNA in the pathogenesis of AF. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to identify the main functions of the differentially expressed genes and AF-related pathways. A total of 219 lncRNAs was found to be differentially expressed between AFs and controls. Among them, 156 were upregulated and 63 were downregulated. Eight out of 10 dysregulated lncRNAs such as uc001eqh.1 were validated by quantitative real-time PCR. GO categories, pathway analyses, and interaction network showed a consistent result that differentially expressed genes contribute to the pathogenesis of AF. In conclusion, the findings of our study provide a perspective on lncRNA in AF and the foundation for further study of the biological functions of lncRNAs in AF.

Guanine nucleotide binding protein-like 3 is a potential prognosis indicator of gastric cancer.

Guanine nucleotide binding protein-like 3 (GNL3) is a GIP-binding nuclear protein that has been reported to be involved in various biological processes, including cell proliferation, cellular senescence and tumorigenesis. This study aimed to investigate the expression level of GNL3 in gastric cancer and to evaluate the relationship between its expression and clinical variables and overall survival of gastric cancer patients. The expression level of GNL3 was examined in 89 human gastric cancer samples using immunohistochemistry (IHC) staining. GNL3 in gastric cancer tissues was significantly upregulated compared with paracancerous tissues. GNL3 expression in adjacent non-cancerous tissues was associated with sex and tumor size. Survival analyses showed that GNL3 expression in both gastric cancer and adjacent non-cancerous tissues were not related to overall survival. However, in the subgroup of patients with larger tumor size (≥ 6 cm), a close association was found between GNL3 expression in gastric cancer tissues and overall survival. GNL3-positive patients had a shorter survival than GNL3-negative patients. Our study suggests that GNL3 might play an important role in the progression of gastric cancer and serve as a biomarker for poor prognosis in gastric cancer patients.

Analysis of genetic variations in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 genes using oligonucleotide microarray.

The cytochrome P450 enzymes play a critical role in the metabolism of many commonly prescribed drugs. Among them, the most important enzymes are highly polymorphic CYP2C9, CYP2C19, CYP2D6 and CYP3A5, which are responsible for about 40% of the metabolism of clinical used drugs. Here we developed a novel CYP450 oligonucleotide microarray that allow for detection of 32 known variations of CYP genes from a single multiplex reaction, including 19 polymorphisms of CYP2D6 gene, 8 polymorphisms of CYP2C9 gene, 4 polymorphisms of CYP2C19 gene and 1 polymorphism of CYP3A5 gene. 229 genomic DNA samples from unrelated Han subjects were analyzed. The microarray results showed to have high call rate and accuracy according to concordance with genotypes identified by independent bidirectional sequencing. Furthermore, we found that the major CYP2C9, CYP2C19, CYP2D6 and CYP3A5 alleles in Chinese Han population were CYP2C9*3 (allelic frequency of 10.7%), CYP2C9*2 (20.31%), CYP2C19*2 (5.68%), CYP2D6*10 (58.52%), CYP2D6*2 (13.76) and CYP3A5*3 (70.69%). With flexible DNA preparation, the microarray can significantly facilitates the process of detecting genetics variations in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 gene and provide safe and effective therapy for individual patients.

Genetic polymorphisms in oxidative stress-related genes are associated with clinical outcome in patients with advanced non-small cell lung cancer receiving tyrosine kinase inhibitors.

Many types of cancer have high antioxidant capacity that effectively scavenges reactive oxygen species and thus protect cancer cells against oxidative damage. The aim of this study was to examine the effect of 20 single nucleotide polymorphisms (SNPs) in 20 oxidative stress-related genes on clinical outcome in 219 patients with advanced non-small cell lung cancer (NSCLC) who were treated with EGFR tyrosine kinase inhibitors (TKIs). We assessed the associations of SNPs with prognosis in all patients as well as stratified by clinical characteristics. Three SNP (rs1695, rs2333227 and rs699512) were significantly associated with overall survival (OS). In a multivariate analysis, rs1695 AA and rs2333227 AG/GG genotypes were identified as independent prognostic factors for poor OS. Stratification analyses revealed that these 3 SNPs remained significantly associated with OS. Furthermore, there was a strong gene-dosage effect of these 3 SNPs on OS that patients with increasing number of unfavorable genotypes had significantly increased death risk. In conclusion, our findings provide the first evidence that genetic variants in oxidative stress-related genes may influence treatment outcome in advanced NSCLC patients receiving EGFR TKIs.

Copy number variation of the Lipoprotein(a) (LPA) gene is associated with coronary artery disease in a southern Han Chinese population.

Copy number variations (CNVs), genomic duplication or deletion events occurring at larger than 1 kb scale, contribute to the complex diseases substantially. Lipoprotein(a) [Lp(a)] is a major inherited risk factor for atherosclerosis and coronary artery disease (CAD). We investigated the association between a CNV of the Lp(a) (LPA) gene and CAD. The case-control study included 271 CAD patients and 207 controls diagnosed by coronary angiography. A taqman real-time fluorescence PCR based technique was developed according to the 2 × 2(-ΔΔCt±SD) calculation method. We detected LPA CNVs with a range of 1, 2 and 3. The 1 copy number carriers had a significantly reduced risk of CAD compared with those with 2 copy number after adjusting for the confounding factors (P < 0.001, OR = 0.38, 95% CI 0.23-0.64). Further stratified analyses suggested a significant protective effect of the 1 copy number in the elderly population (P = 0.008), females (P = 0.007) as well as in populations with non-hyperlipidemia (P = 0.003), hypertension (P = 0.001), non-smoking (P < 0.001) and high Lp(a) (≥ 0.3 g/L) levels (P = 0.001). The 1 copy number of the LPA gene may be an independent protective factor of CAD in a southern Han Chinese population, particularly in females and the elderly.