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Purpose: Exploring new understanding of genetic factors can help reveal the etiology of MPM and improve the survival rate of patients with MPM. Methods: We explored the expression pattern in MPM across GEO, DAVID, HMDD, and miRNet. The PPI networks of the intersection targets were constructed by STRING and Cytoscape, and the hub genes were selected by plugin cytoHubba. The survival analysis of hub genes was also carried out based on the GEPIA and UALCAN database. The immune subtype and infiltration analyses were performed using TISTDB and TIMER database. Results: A total of 251 DEGs were detected. GO and KEGG pathway analysis revealed that DEGs were significantly enriched in extracellular matrix organization, ECM-receptor interaction. The PPI network was assessed, and the top 10 hub genes were identified by evaluating degrees. High expression level of CDH2, COL3A1, CAV1 was associated with worse prognostic value in MPM. For different immune subtypes, significant connection with CDH2/COL3A1/CAV1 expression existed in MPM. The correlation between immune cells and hub genes showed that CAV1 was positively correlated with Dendritic cells, CDH2 was positively correlated with Dendritic cells, while it was negatively correlated with Neutrophil. COL3A1 expression was positively associated with infiltration levels of Macrophages, whereas negative association with Neutrophil. Furthermore, Neutrophil and CDH2 was significantly correlated with the clinical outcomes of MPM. Conclusion: CDH2, COL3A1, and CAV1 may serve as a promising prognostic biomarker in MPM, in particular, the correlation between CDH2 and Neutrophil is one of the critical factors affecting MPM prognosis.

Introduction: Noise-induced hearing loss (NIHL) is a common occupational disease that represents an irreversible hearing damage to the auditory system. It has been identified as a complicated disease involving both environmental and genetic factors. More efforts need to be made to explore the genes associated with susceptibility to NIHL. The main aim of this research is to detect the associations between SIK3 polymorphisms and NIHL susceptibility in Han people in China. Methods: A case-control study was performed in 586 cases and 639 controls in a textile factory matched for sex, age, smoking, drinking, work time with noise, and intensity of noise exposure. Three single nucleotide polymorphisms (SNPs) (rs493134, rs6589574, and rs7121898) of SIK3 were genotyped in the participants. Then, the main influences of the SNPs on and their interactions with NIHL were assessed. Results: Under the allelic model, distributions of rs493134 T, rs6589574 G, and rs7121898 A in the NIHL group are statistically different from those of the normal group (p = 0.001, p < 0.001, and p = 0.019, respectively). The following haplotype analysis shows that TAA (rs493134-rs6589574-rs7121898) may have a protective effect, while TGA (rs493134-rs6589574-rs7121898) (OR = 1.49, 95% CI = 1.25–1.79) may be a risk factor for NIHL. Multifactor dimensionality reduction analysis shows that the interaction of the 3 selected SNPs is associated with NIHL susceptibility (OR = 1.88, 95% CI = 1.50–2.36). Conclusion: The results suggest that 3 SNPs (rs493134, rs6589574, and rs7121898) of SIK3 may be an important part of NIHL susceptibility and can be applied in the prevention, early diagnosis, and treatment of NIHL in noise-exposed Chinese workers.

Objectives NIHL is a disease with irreversible damage caused by multi-factor interaction, and the STAT3 is an essential protein with signal transduction and transcription functions. This study is aimed to explore the effect of STAT3 polymorphism on individual susceptibility to NIHL individuals, and to further examine the interaction between lifestyles and NIHL in the dominant model . Methods This study was designed a case-control study and included 609 NIHL cases and 611 healthy hearing controls from the Jiangsu province of China. By collecting the lifestyle and demographic information of the study participants, genotyping the collected blood samples, and performing Real-time Quantitative PCR (qRT-PCR) to analyze and investigate the potential association between STAT3 SNPs and NIHL. Results Statistical analysis results show that individuals carrying the C allele of rs1053023 and rs1053005 were more likely to develop NIHL than individuals carrying the T allele (OR = 1.367, 95% CI = 1.148–1.628, P = 0.0001 and OR = 1.37, 95% CI = 1.147–1.636, P = 0.001). In the dominant model (TC/CC genotype and TT genotype), stratified analysis of lifestyle, we found that people who smoke regularly are more likely to suffer from NIHL than non-smokers or occasional smokers. Besides, the expression of STAT3 was higher in NIHL cases by real-time quantitative PCR. Conclusion Gene polymorphisms, rs1053023 and rs1053005, from STAT3, are associated with NIHL and C alleles of rs1053023 and rs1053005 within STAT3 may become biomarkers for workers exposed to noise.

Objectives.The purpose of this study was to investigate the correlation between single-nucleotide polymorphism (SNP) in 3′UTR of XPO5 gene and the occurrence of noise-induced hearing loss (NIHL), and to further explore the regulatory mechanism of miRNAs in NIHL on XPO5 gene. Methods.We conducted a case-control study involving 1040 cases and 1060 controls. The effects of SNPs on XPO5 expression were studied by genotyping, real-time polymerase chain reaction (qPCR), cell transfection, and the dual-luciferase reporter assay. Results.We genotyped four SNPs (rs2257082, rs11077, rs7755135, and rs1106841) in the XPO5 gene. The rs2257082 AG/GG carriers have special connection to an increased risk of noise-induced hearing loss compared to the AA carriers. The rs11077TG/GG carriers had a significantly increased association with NIHL susceptibility than the TT carriers. There was a higher risk of NIHL in the XPO5 gene rs7755135 CC carriers than in the TT carriers. No statistically significant correlation was obtained with respect to SNPrs1106841. Functional experiments showed that the rs11077 change might inhibit the interaction between miRNAs (miRNA-4763-5p, miRNA-5002-3p, and miRNA-617) and XPO5, with rs11077G allele resulting in overexpression of XPO5. Conclusion. The genetic polymorphism, rs11077, within XPO5 is associated with the risk of noise-induced hearing loss in a Chinese population.

Objective We aim to investigate whether genetic mutations in three important base excision repair genes (OGG1, APEX1, and XRCC1) may influence susceptibility to noise-induced hearing loss. Methods Three SNPs in OGG1, APEX1, and XRCC1 were genotyped from noise exposed workers who were classified into susceptible and resistant individuals. Results: Results showed that the rs1799782 TT genotype located in the XRCC1 coding region and rs1130409 GG/GT in the APEX1 coding region were associated with increased risk for noise-induced hearing loss. Compared to the rs1799782 C allele frequency, the T allele frequency increased in the sensitive group (OR = 1.51). Rs1130409 G allele frequency also increased in the sensitive group compared to the resistant group (OR = 1.59). Conclusions XRCC1 rs1799782 and APEX1 rs1130409 may have potential as biomarkers for screening susceptibility to NIHL in workers exposed severe noise.

Objective. Noise-induced hearing loss (NIHL) is one of the most common occupational health risks in both developed and industrialized countries. It occurs as a result of interactions between genetic and environmental factors. Nevertheless, inherited genetic factors contributing to NIHL are not well understood. Therefore, we aim to investigate whether genetic mutations in three important base excision repair genes (OGG1,APEX1, andXRCC1) may influence susceptibility to NIHL.Methods. Three SNPs inOGG1,APEX1, andXRCC1were genotyped from 1170 noise-exposed workers and were classified into 117 most susceptible and 117 most resistant individuals.Results. Results showed that the rs1799782 TT genotype located in theXRCC1coding region and rs1130409 GG/GT in theAPEX1coding region were associated with increased risk for NIHL in a Chinese population. Compared to the rs1799782 C allele frequency, the T allele frequency was increased in the sensitive group (adjustedOR=1.51,95%CI=1.01to 2.26,P=0.043). The rs1130409 G allele frequency was also increased in the sensitive group compared to the resistant group (adjustedOR=1.59,95%CI=1.10to 2.31,P=0.015). Moreover, rs1130409 and drinking had a statistically significant interaction (P=0.0002), while rs1799782, rs1130409, and smoking also had a statistically significant interaction (P<0.0001).Conclusions.XRCC1rs1799782 andAPEX1rs1130409 may have potential as biomarkers for the screening of susceptibility to NIHL in workers exposed severe noise.

Noise-induced hearing loss (NIHL), one of the most widespread occupational health risks worldwide, is a kind of complex disorder resulting from both genetic and environmental factors. KCNQ4 channels are crucial to the internal ear potassium recycling. To explore whether KCNQ4 polymorphism is associated with individual susceptibility to NIHL, we performed this genetic association study on 571 NIHL cases and 639 normal hearing controls selected from about 2700 Chinese noise-exposed workers. General information and audiometric data were obtained through questionnaires and pure-tone audiometry (PTA). DNA samples were collected and genotyping for three selected SNPs (rs709688, rs2769256 and rs4660468) was performed. Significant differences were observed between cases and controls for the genotype frequency and allele frequency in rs4660468, suggesting that rs4660468 CT/TT genotype and T allele may be risk factors for NIHL. In subjects exposed to noise for more than 16 years (OR = 1.23, 95% CI = 1.09–1.53) and those who exposed to noise >92 dB (OR = 1.29, 95% CI = 1.08–1.69), increased risks of NIHL were found after stratified analysis for rs4660468. Our results suggest that rs4660468 T allele of KCNQ4 involves with a higher risk of NIHL and could be one biomarker of susceptibility for Chinese noise exposed workers.

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.