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Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics. Multiple synchronous lung cancers (MSLCs) are a subtype of lung cancer. Here the authors characterise MSLCs using single cell RNA sequencing, single cell TCR sequencing and bulk whole-exome sequencing to investigate the mutations that arise in and are associated with invasive adenocarcinoma development, and immune microenvironment changes in this process. [ABSTRACT FROM AUTHOR]

Background and purpose: We analyzed the distribution of metastatic sites and survival of lung cancer patients with metastases based on hospital registration to provide real-world data support for the treatment and survival management of lung cancer patients. Methods: A total of 1 490 lung cancer patients who developed metastasis during the follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were enrolled in this study. Medical records review, telephone visits and death registry data linkage were applied in collecting endpoint data. The effects of age at diagnosis, gender and histological subtype on the distribution of metastases were studied. The Kaplan-Meier method was used to evaluate the overall survival (OS) rates of different metastatic sites. Results: The median follow-up time was 40.8 months. During the follow-up period, 937 cases died from all causes. 67.7% of patients only had single-site metastasis, while 32.3% of patients had multiple-site metastases. The common metastatic sites were bone (33.8%), brain (33.6%), lung (22.8%), liver (12.0%) and adrenal gland (3.7%). Female patients had more metastases to brain (37.8% vs 31.4%). Younger patients were more likely to develop multiple-site metastases, and small cell carcinomas patients had more brain metastases (47.2%) and liver metastases (20.9%). Lung metastasis featured relatively best survival (1-year OS rate: 78.3%, 3-year OS rate: 47.1%, 5-year OS rate: 29.5%), whereas liver metastasis had relatively the worst prognosis (1-year OS rate: 46.4%, 3-year OS rate: 15.2%, 5-year OS rate: 3.6%). Conclusion: The proportions of bone and brain metastases in lung cancer patients with metastasis are high. The distribution of metastatic sites is associated with gender, age at diagnosis and histological type. The prognosis of patient with different metastatic sites is different. Mechanisms or clinical treatment plans can be studied for different metastatic sites to improve the prognosis of late-stage lung cancer patients in future research.

Lung cancer is a leading cause of cancer death all around the world. Long non-coding RNAs (lncRNAs) have been confirmed to be involved in carcinogenesis of malignancies. However, the molecular mechanism of most lncRNAs in various kinds of cancers remains unclear. LncRNA HOTAIR and HNRNPA1 are reported to play an oncogenic role in non-small cell lung cancer, and the overexpression of HNRNPA1 is shown to promote the proliferation of lung adenocarcinoma cells. In our study, we find that the overexpression of HOTAIR could promote the proliferation and overexpression of miR-149-5p could inhibit the proliferation of lung cancer cells. Flow cytometric analysis determines that overexpression of miR-149-5p induces cell cycle arrest in the G0/G1 phases, whereas overexpression of HOTAIR decreases the proportion of G0/G1phase cells. Also, overexpression of HOTAIR promotes the migration and invasion ability of lung cancer cells, confirmed by the wound-healing and transwell assays, which are suppressed by overexpression of miR-149-5p. Furthermore, the dual-luciferase reporter assay indicates that miR-149-5p could bind both HOTAIR and the 3′UTR of HNRNPA1. In summary, we find that HOTAIR can regulate HNRNPA1 expression through a ceRNA mechanism by sequester miR-149-5p, which post-transcriptionally targets HNRNPA1, thus promoting lung cancer progression. [ABSTRACT FROM AUTHOR]

Objectives: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated and overexpressed in many cancers, including non–small‐cell lung cancer (NSCLC). We recently developed HJC0152 as an orally active STAT3 inhibitor. This study focused on investigating HJC0152's effect and mechanism of action in NSCLC. Materials and methods: We analysed cell proliferation by MTT assays, cell migration by wound healing and transwell assays, protein levels by Western blot, and apoptosis and reactive oxygen species (ROS) level by flow cytometry. A nude mouse tumorigenesis model was established for in vivo experiment. UHPLC‐QTOF/MS was used for untargeted metabolomic relative quantitation analysis. Results: We found that HJC0152 exhibited activity against human NSCLC cells in vitro and NSCLC xenograft tumours in vivo via regulating STAT3 signalling and metabolism. HJC0152 efficiently reduced NSCLC cell proliferation, promoted ROS generation, induced apoptosis, triggered DNA damage and reduced motility in A549 and H460 NSCLC cells. Moreover, HJC0152 significantly inhibited the growth of A549 xenograft tumours in vivo. HJC0152 also affected metabolism, significantly decreasing and perturbating levels of several metabolites in the purine, glutathione and pyrimidine metabolism pathways. Conclusions: HJC0152 reduces cellular capacity to scavenge free radicals, leading to ROS generation and accumulation and apoptosis. This study provides a rationale for further developing HJC0152 as a potential therapy for NSCLC and provides insights into the mechanisms by which HJC0152 exerts its anti‐cancer effects. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are a new class of potential biomarkers and therapeutic targets for cancer. In this study, we chose four single nucleotide polymorphisms (SNPs) in lncRNA-PCAT1 (rs1026411 G>A, rs12543663 A>C, rs710886 T>C, and rs16901904 T>C) to investigate the association between genetic variant in lncRNA-PCAT1 and susceptibility to lung cancer. The study was a hospital-based case–control study including 561 cancer-free controls and 468 lung cancer cases. Genotyping of four SNPs was conducted by using Taqman® allelic discrimination methods. All statistical analyses were performed by using IBM SPSS Statistics 22 software. We failed to find significant associations between four SNPs and lung cancer risk in all models. However, polymorphisms in rs1026411 and rs710886 were observed to have significant associations with susceptibility to non-small cell lung cancer (AG vs. GG: odds ratio [OR]a = 0.701, p* = 0.020 and AA+AG vs. GG: ORa = 0.711 [superscript "a" refers to OR adjusted by age, gender, and smoking], p* = 0.017 [asterisks "*" refers to p adjusted by age, gender, and smoking] for rs1026411; CT vs. TT: ORa = 0.723, p* = 0.047 and CC+CT vs. TT: ORa = 0.729, p* = 0.038 for rs710886). Besides, the rs1026411 polymorphism had a similar association with lung adenocarcinoma risk (AG vs. GG: ORa = 0.663, p* = 0.019 and AA+AG vs. GG: ORa = 0.685, p* = 0.020). Polymorphisms in rs710886 and rs16901904 were observed to be associated with lung squamous cell carcinoma risk (CC+CT vs. TT: ORa = 0.638, p* = 0.040 for rs710886; CC vs. TT: ORa = 2.582, p* = 0.033 and CC vs. TT+CT: ORa = 2.381, p* = 0.048 for rs16901904). In addition, there were no significant results in gene–environmental interactions in both additive and multiplicative models. Our results suggested that polymorphisms in lncRNA-PCAT1 might be associated with lung cancer susceptibility in a northeastern Chinese population. The results of gene–environmental interactions were not significant in lung cancer. [ABSTRACT FROM AUTHOR]

Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026–1.723, p = 0.031 and adjusted OR = 1.450, 95% CI = 1.112–1.890, p = 0.006, respectively). The results of crossover analysis revealed that rs3733845 and rs3733846 risk genotypes along with cooking oil exposure increased lung cancer risk by 1.862-fold and 2.260-fold, respectively (adjusted OR = 1.862, 95% CI = 1.105–3.138, p = 0.020 for rs3733845; adjusted OR = 2.260, 95% CI = 1.354–3.769, p = 0.002 for rs3733846). There was positive multiplicative interaction between the two SNPs and cooking oil fume exposure (adjusted OR = 1.362, 95% CI = 1.078–1.719, p = 0.009 for oil × rs3733845; adjusted OR = 1.399, 95% CI = 1.122–1.745, p = 0.003 for oil × rs3733846). In nonsmoking females, rs3733845 and rs3733846 polymorphisms might be associated with lung adenocarcinoma risk. Moreover, the interactions between the two SNPs and cooking oil fume exposure were statistically significant on a multiplicative scale rather than an addictive scale. [ABSTRACT FROM AUTHOR]

CYP24A1 plays important roles in antiproliferative effects, which have been proved in many human tumor cells. Polymorphisms in CYP24A1 may affect the risk of lung cancer, but the results remained inconclusive. To enhance the understanding of possible relationship between CYP24A1 polymorphism rs6068816 and lung cancer risks, we first carried out this case–control study among Chinese female nonsmokers, including 345 lung cancer patients and 351 noncancer controls. Our results revealed that individuals carrying CT and CC genotype were associated with decreasing lung cancer risk (adjusted odds ratios were 0.71 and 0.59, and 95% confidence intervals were 0.52–0.97 and 0.35–0.99, p-values were 0.031 and 0.048, respectively). Patients carrying allele-T showed lower hazard risks, especially in adenocarcinoma and advanced stage cancers. We also found that subjects with allele-T showed a relatively low risk of lung cancer when they were exposed to oil fume. But neither additive scale nor multiplicative scale revealed interactions between allele-T and environmental exposures, including oil fume, coal fuel fume, and passive smoking. Overall, these findings indicated that CYP24A1 polymorphism rs6068816 could be significantly associated with susceptibility of lung cancer in Chinese female nonsmokers. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNA) maternal-expressed gene 3 (MEG3) is associated with proliferation of various tumor cells and has decreased expression in many types of cancers. In this study, we aimed at demonstrating the association between MEG3 polymorphisms and the risk of lung cancer in northeast China. There were 526 lung cancer patients and 526 healthy controls included in this hospital-based case-control study. The genotyping of two polymorphisms, rs7158663 G > A and rs4081134 G>A, was performed by the Taqman allelic discrimination method. We found that MEG3 rs4081134-AA may be associated with the risk of lung cancer (AA vs. GG: adjusted odds ratio [OR] = 0.487, confidence interval [95% CI] = 0.257–0.897, p = 0.030; AA vs. AG+GG: adjusted OR = 0.522, 95% CI = 0.274–0.992, p = 0.047). Similar associations in several subgroups were found in subsequent stratified analysis. Further, there were no statistically significant interactions of rs4081134 polymorphism and smoking to lung cancer susceptibility. In addition, the associations between the MEG3 rs7158663 polymorphism and lung cancer susceptibility were not found. These results indicate that the MEG3 rs4081134 polymorphism was significantly associated with lung cancer susceptibility in the Chinese population. [ABSTRACT FROM AUTHOR]

Purpose: HOX transcript antisense RNA (HOTAIR) plays important roles in carcinogenesis of various kinds of malignant tumors, including lung cancer. Single nucleotide polymorphisms (SNPs) in HOTAIR were reported to be associated with susceptibility of several kinds of cancers. The present study assessed the associations between three SNPs (rs4759314, rs12826786, and rs920778) and lung cancer susceptibility, as well as gene–environment interaction between smoking exposure and the polymorphisms. Patients and methods: A case–control study including 551 patients and 543 healthy controls was performed. The associations between SNPs and lung cancer susceptibility were assessed by logistic regression model. Results: rs4759314 was observed to increase the susceptibility of lung cancer, lung adenocarcinoma, squamous lung cancer, and small cell lung cancer statistically significantly (OR of 4.048 for lung cancer; 3.584 for lung adenocarcinoma; 4.671 for squamous lung cancer; 4.502 for small cell lung cancer). In stratified analysis for sex and smoking exposure, rs4759314 GG and AG genotype was also observed to increase the risk of lung cancer statistically significantly (OR of 5.221 for male; 3.491 for female; 3.653 for nonsmoking individuals; 4.458 for smoking individuals). Results of gene–environment interaction analysis showed that there was no interaction between smoking exposure and rs4759314 on additive scale. Results of logistic regression model suggested that the interaction between smoking and rs4759314 was statistically significant on multiplicative scale. rs12826786 CT genotype carriers and T allele could decrease the risk of developing lung cancer (OR of 0.751 for CT carriers; 0.785 for T allele), and in dominant model, TC and TT genotype carriers also have a 0.249-fold decrease risk compared with CC genotype carriers. In stratified analysis for smoking exposure, TC and TT have a 0.432-fold decreased risk compared with CC genotype carriers. Conclusion: HOTAIR rs4759314 and rs12826786 were associated with lung cancer susceptibility in Chinese Han population. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) play important roles in the development of human cancers. This is the first case–control study of the association between specific polymorphisms in lncRNA genes and the risk of lung cancer, as well as the gene–environment interaction between the polymorphisms and cooking oil fume exposure in Chinese never-smoking females. A hospital-based case–control study was carried out in Shenyang, Liaoning province. The study included 395 cases and 556 controls. The polymorphisms of rs4785367, rs3803662, rs10750417, and rs1814343 in lncRNA genes were analyzed. The gene–environment interactions were explored on both additive and multiplicative scale. In addition, the results were listed as follows: for rs3803662, compared with the individuals carrying homozygous TT genotype, those with homozygous CC genotype had the decreased risk of lung cancer (adjusted odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.40–0.92, p = 0.018). As for rs4785367, compared with homozygous TT, homozygous CC could lessen the risk of lung cancer (adjusted OR = 0.54, 95% CI = 0.33–0.89, p = 0.016). The recessive models of rs3803662 and rs4785367 showed significant association (adjusted OR = 0.65, 95% CIs = 0.44–0.97, p = 0.033; adjusted OR = 0.54, 95% CIs = 0.33–0.88, p = 0.014). The C allele of rs3803662 was suggested to be protective allele of lung cancer (adjusted OR = 0.80, 95% CI = 0.66–0.97, p = 0.023). However, rs10750417 and rs1814343 polymorphisms were not significantly associated with lung cancer risks. The measures of additive interaction and logistic models suggested that the gene–environment interactions were not statistically significant on both additive and multiplicative scales. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between rs7248320 in lncRNA AC008392.1 and the risk of lung cancer, this case��control study was carried out in a Chinese population. This study also evaluated the gene��environment interaction between rs7248320 and exposure to smoking status on the risk of lung cancer. Patients and methods: We conducted a hospital-based case��control study including 512 lung cancer cases and 588 healthy controls. The association between rs7248320 and the risk of lung cancer was analyzed, and the gene��environment interaction was estimated on an additive scale. Results: The variant genotype of rs7248320 was significantly related to the risk of non-small-cell lung cancer (NSCLC). Individuals carrying homozygous GG genotype had decreased risk of NSCLC, compared with individuals carrying the homozygous wild AA genotype/heterozygote GA genotype (adjusted odds ratio [OR] =0.653, 95% confidence interval [CI] =0.442��0.966, P=0.033). Moreover, in the subgroup of ages, there were statistically significant associations between rs7248320 and the risk of lung cancer and NSCLC in the population over 60 years of age. Compared with individuals carrying genotypes AA/GA, individuals with genotype GG had the lower risk of lung cancer and NSCLC (adjusted ORs were 0.579 and 0.433, 95% CIs were 0.338��0.994 and 0.231��0.811, P-values were 0.048 and 0.009, respectively). Compared with homozygote AA, the homozygote GG was associated with a decreased risk in NSCLC (OR =0.456, 95% CI =0.235��0.887, P=0.021). There were no statistically significant results in gene��environment interactions on an additive scale. Conclusion: These findings suggest that lncRNA AC008392.1 rs7248320 may be involved in genetic susceptibility to NSCLC in a Chinese population. [ABSTRACT FROM AUTHOR]

Purpose: We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. Methods: We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. Results: Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4- ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. Conclusions: ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses. [ABSTRACT FROM AUTHOR]

Germacrone (GM) displays a wide range of antitumor, antioxidant and anti-inflammatory effects; however, to the best of our knowledge, the effects of GM on lung cancer cell apoptosis and cell cycle arrest have not been previously reported. The aim of the present study was to investigate discussed the effects of GM on the apoptosis and cycle arrest of lung cancer cells. Cell viability, proliferation and apoptosis were assessed by performing Cell Counting Kit-8, colony formation and TUNEL assays, respectively. Western blotting was performed to detect the expression levels of apoptosis-, cell cycle- and Akt/MDM2 proto-oncogene (MDM2)/p53 signaling pathway-related proteins. Compared with the control group, 50, 100 and 200 µM GM significantly inhibited lung cancer cell proliferation, but significantly induced cell apoptosis and G1/S cell cycle arrest. GM also significantly altered the expression levels of Akt/MDM2/p53 signaling pathway-related proteins compared with the control group. Administration of Akt activator SC79 significantly reversed GM-mediated antiproliferative, proapoptotic and pro-cell cycle arrest effects in lung cancer cells. Therefore, the results of the present study demonstrated that GM induced lung cancer cell apoptosis and cell cycle arrest via the Akt/MDM2/p53 signaling pathway. [ABSTRACT FROM AUTHOR]

Two-dimensional ultrasound (US) and color doppler flow imaging are associated with certain limitations in the preprocedural evaluation and design of the puncture path for biopsies of thoracic lesions, such as a poorly defined boundary between the tumor and the atelectatic lesions in central lung cancer with atelectasis. Contrast-enhanced ultrasound (CEUS) can be valuable in the preoperative evaluation of the biopsy site and in increasing the accuracy of the biopsy. The present study investigated the value of clinical application of CEUS in US-guided core needle biopsy (US-CNB) in improving the diagnostic accuracy in thoracic lesions. A total of 120 patients with first-stage thoracic lesions from the Affiliated Tumor Hospital of Guangxi Medical University who underwent US-CNB were recruited and randomnly assigned to a conventional US group (n=66) and a CEUS group (n=54). All patients underwent preoperative evaluation and US-guided puncture of thoracic lesions. The intergroup differences in sonographic features, biopsy duration, biopsy success rate and complications were assessed. The CEUS group had a higher rate of detection of necrotic tissue (40.7% vs. 16.7%; χ2=8.633; P=0.003) and change of initial puncture path (48.1%) compared with the US group. In central lung cancer with atelectasis, the ability to distinguish between tumor and atelectasis was higher in the CEUS group compared with the conventional US group (31.5 vs. 7.6%; χ2=11.336; P=0.001). In addition, the CEUS group had a higher puncture success (96.3 vs. 80.3%; χ2=6.946; P=0.008) and a lower complication rate (3.7% vs. 18.2%; χ2=6.041; P=0.014) compared with the US group. CEUS can identify necrotic areas and occult tumors within atelectatic lung tissue and can be used for guiding puncture biopsy of thoracic lesions to improve the diagnostic accuracy with greater comparative clinical utility than conventional US. Pre-biopsy CEUS is especially useful for patients undergoing repeated US-CNB and those with hypovascular lesions, atelectasis or necrosis. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs play pivotal roles in the carcinogenesis of multiple types of cancers. This study is firstly to evaluate influence of rs4848320 and rs1110839 polymorphisms in long non-coding RNA AC016683.6 on the susceptibility of lung cancer. Methods: The present study was a hospital-based case–control study with 434 lung cancer patients and 593 cancer-free controls. Genotyping of the two SNPs detected by Taqman® allelic discrimination method. Results: There were no statistically significant associations between rs4848320 and rs1110839 polymorphisms in AC016683.6 and risk of lung cancer in overall population. However, in the smoking population, rs4848320 and rs1110839 polymorphisms significantly increased the risk of lung cancer in dominant and homozygous models (Rs4848320: P = 0.029; Rs1110839: P = 0.034), respectively. In male population, rs1110839 genetic variant was related to the risk of lung cancer in all genetic models (GG vs. TT: P = 0.008; Dominant model: P = 0.029; Recessive model: P = 0.027) rather than heterozygous model. The crossover analyses provided rs4848320 and rs1110839 risk genotypes carriers combined with smoking exposure 2.218-fold, 1.755-fold increased risk of lung cancer (Rs4848320: P = 0.005; Rs1110839: P = 0.017). Additionally, there were significantly positive multiplicative interaction of rs4848320 polymorphism with smoking status, with adjusted OR of 2.244 (1.162–4.334), but rs1110839 polymorphism did not exist. Conclusions: Rs4848320 and rs1110839 polymorphisms may be associated with lung cancer susceptibility. Interaction of rs4848320 risk genotypes with smoking exposure may strengthen the risk effect on lung cancer. [ABSTRACT FROM AUTHOR]

An abstract of the study "Frequency of Well-Identified Oncogenic Driver Mutations in Lung Adenocarcinoma of Smokers Varies With Histological Subtypes in Line With IASLC/ATS/ERS Classification," by Hang Li and colleagues is presented.

Long non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is a novel lncRNA localized specifically to nuclear paraspeckles. The study analyses the association between NEAT1 genetic polymorphisms and the susceptibility of lung cancer in a Chinese Northeast Population. The NEAT1 rs512715 and rs2239895 genetic polymorphisms were genotyped in 462 lung cancer cases and 559 controls by a Real-Time Polymerase Chain Reaction (PCR) with the TaqMan discrimination assay. Our study found that the polymorphisms of two SNPs increased or decreased the risk of lung cancer were not obvious, but statistical significance in non-small cell lung cancer and lung squamous cell carcinoma can be observed. Compared with homozygous CC genotype carriers, the GC genotype of rs2239895 was positively related to the risk of lung squamous cell carcinoma (OR 1.805, 95% CI, 1.168–2.789, P = 0.008). Similarly, associations between rs2239895 and lung squamous cell carcinoma risk were found (CC + GC vs. GG, OR 1.668, 95%CI, 1.093–2.545, P = 0.018) in dominant model. In stratified analysis for age, rs2239895 GC genotype was observed to increase the risk of non-small-cell lung cancer compared with CC genotype (OR 1.562, 95%CI, 1.029–2.371, P = 0.036). However, the study showed that negative correlation the lung cancer risk and rs512715 polymorphisms. There was no remarkable relationship between the both additive and multiplicative model about the two SNPs. The polymorphisms rs2239895 were associated with the risk of lung squamous cell carcinoma. The interaction between the two SNPs and the cigarette smoking was no notable difference. [ABSTRACT FROM AUTHOR]

Essential metals play important roles in the carcinogenic process. However, seldom longitudinal investigations have evaluated their roles in lung cancer development. We aimed to investigate the associations between multiple essential metals and lung cancer incidence and to explore the potential mechanisms. A nested case-control study of 440 incident lung cancer cases and 1:3 frequency matched 1320 healthy controls from the Dongfeng-Tongji Cohort was conducted. The baseline plasma concentrations of 11 essential metals (cobalt, copper, iron, manganese, molybdenum, rubidium, selenium, strontium, stannum, vanadium, and zinc) were measured, and their associations with lung cancer incidence were estimated. Effect of positive metal (zinc) on 4-year telomere attrition was then evaluated among an occupational cohort of 724 workers. We also assessed the transcriptional regulation effects of plasma zinc on mRNA expression profiles, and the expressions of zinc-related genes were further compared in pair-wised lung tumor and normal tissues. Elevated plasma level of zinc was associated with lower incident risk of lung cancer [OR (95% CI) = 0.89 (0.79, 0.99)] and decreased 4-year telomere attrition [β (95% CI) = −0.73 (−1.27, −0.19)]. These effects were pronounced among males. In particularly, zinc could regulate the expressions of 8 cancer-related genes, including SOD1 , APE , TP53BP1 , WDR33 , LAPTM4B , TRIT1 , HUWE1 , and ZNF813 , which were over-expressed in lung tumor tissues. We propose that high plasma zinc could prevent incident lung cancer, probably by slowing down telomere attrition and regulating the expressions of cancer-related genes. These results provided a new insight into lung cancer prevention. • Increased plasma zinc level was associated with a lower risk of lung cancer. • High plasma zinc level was associated with decreased telomere length attrition. • Plasma zinc level was associated with the expressions of 13 cancer-related genes. • 8 of the 13 cancer-related genes were up-regulated in lung tumor tissues. [ABSTRACT FROM AUTHOR]

Abstract: Background: To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas. Methods: Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations. Results: There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P =0.007), whereas all the 15 tumors harboring RET fusions were ≤3cm in diameter (P =0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P <0.001), cribriform pattern (P <0.001), signet ring cells (P <0.001) and hepatoid cytology (P <0.001). No significant difference in relapse-free survival (P =0.147) and overall survival (P =0.444) was observed between fusion-positive and fusion-negative patients. Conclusions: This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening. [Copyright &y& Elsevier]

Benzo[a]pyrene (B[a]P) is a typical carcinogen associated with increased lung cancer risk, but the underlying mechanisms remain unclear. This study aimed to investigate epigenome-wide DNA methylation associated with B[a]P exposure and their mediation effects on B[a]P-lung cancer association in two lung cancer case-control studies of 462 subjects. Their plasma levels of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts and genome-wide DNA methylations were separately detected in peripheral blood by using enzyme-linked immunosorbent assay (ELISA) and genome-wide methylation arrays. The epigenome-wide meta-analysis was performed to analyze the associations between BPDE-Alb adducts and DNA methylations. Mediation analysis was applied to assess effect of DNA methylation on the B[a]P-lung cancer association. We identified 15 CpGs associated with BPDE-Alb adducts (P −meta < 1.0 × 10−5), among which the methylation levels at five loci (cg06245338, cg24256211, cg15107887, cg02211741, and cg04354393 annotated to UBE2O , SAMD4A , ACBD6 , DGKZ , and SLFN13 , respectively) mediated a separate 38.5%, 29.2%, 41.5%, 47.7%, 56.5%, and a joint 58.2% of the association between BPDE-Alb adducts and lung cancer risk. Compared to the traditional factors [area under the curve (AUC) = 0.788], addition of these CpGs exerted improved discriminations for lung cancer, with AUC ranging 0.828–0.861. Our results highlight DNA methylation alterations as potential mediators in lung tumorigenesis induced by B[a]P exposure. [Display omitted] • We conducted the first epigenome-wide DNA methylation analysis of B[a]P exposure. • Exposure to B[a]P is significantly associated with methylation levels at 15 CpGs. • B[a]P-associated CpGs mediate 30~60% of its association with lung cancer. • DNA methylation plays a critical role in lung tumorigenesis induced by B[a]P. [ABSTRACT FROM AUTHOR]