Histological Types Of Lung Cancer Research Articles

Identification of key candidate genes associated with prognosis of lung adenocarcinoma by integrated bioinformatical analysis.

BackgroundLung adenocarcinoma (LUAD) is the most frequent histologic type of lung cancer and the morbidity of LUAD is increasing rapidly in the worldwide. But the mechanism of LUAD is still largely unknown.MethodsIn this study, we analyzed three microarrays of gene expression profiles, containing 196 LUAD samples and 137 normal samples, to explore the potential key candidate genes in LUAD by integrated bioinformatical analysis.ResultsA total of 240 shared differentially expressed genes (DEGs) were identified and pathways enrichment were analyzed. DEGs-associated protein-protein interaction (PPI) network was constructed and top 20 hub genes were established by calculating the degree of connectivity. We further validated these genes in TCGA and GTEx projects, and found all of these hub genes were differentially expressed in LUAD patients except TIMP1 and FOS. In these candidate genes, ten genes (TPX2, CENPF, TYMS, PRC1, NEK2, CCNB2, KIAA0101, CDC20, TOP2A and SPP1) were confirmed to associate with the prognosis of LUAD. Out of these ten genes, CENPF had the highest genetic alteration at a rate of 4% in LUAD patients, and the expression of CENPF was significantly increased in different subgroups of all age, gender, race, smoking condition and cancer stage groups of LUAD patients.ConclusionsOur study contributes to comprehend the role of genes in LUAD and provides possible therapeutic targets for further clinical application.

54 Poster Discussion - The integrated stress response exposes a therapeutic vulnerability in KRAS driven lung cancer

Background: Mutations in KRAS account for ∼25% of lung cancer cases and are refractory to therapy. Tumors with KRAS mutations encounter increased levels of genotoxic, proteotoxic and metabolic stress, which disrupt proliferation and homeostasis. The Integrated Stress Response (ISR) plays a key role in adaptation to stress via phosphorylation of eukaryotic initiation factor 2 (p-eIF2). When ISR is activated, p-eIF2 mediates translational and transcriptional reprogramming of genes with roles in survival and adaptation. Here we demonstrate the importance of ISR in the development of KRAS lung adenocarcinoma (LUAD), the most common histological type of lung cancer and a leading cause of cancer death worldwide.

Akciğer adenokarsinomu tonsil metastazı: nadir bir olgu

Tonsil cancers account for 0,3% of all cancers and 6,7% of head and neck cancers. However, metastasis to tonsil is extremely rare. The kidney, skin, lung and breast are most common sites of primary tumor. Different histological types of lung cancer can metastase to tonsil. We present a case with left tonsil metastasis of lung adenocarcinoma. The most important point with our case is that the patient had his complaints for 1 year and received irrelevant treatments. As in our case, tonsil neoplasms may present with peritonsillar abscess. However, patients with history of cancer and prolonged complaints need a thorough evaluation of suspicious tonsil enlargement. Metastases may be synchronous with the lung tumor or may be observed before or after the treatment of primary tumor. Careful examination and radiological evaluation are very important in cancer patients; and biopsy must be performed in all cases with clinical suspicion.

Fully-Connected Neural Networks with Reduced Parameterization for Predicting Histological Types of Lung Cancer from Somatic Mutations

Several challenges appear in the application of deep learning to genomic data. First, the dimensionality of input can be orders of magnitude greater than the number of samples, forcing the model to be prone to overfitting the training dataset. Second, each input variable’s contribution to the prediction is usually difficult to interpret, owing to multiple nonlinear operations. Third, genetic data features sometimes have no innate structure. To alleviate these problems, we propose a modification to Diet Networks by adding element-wise input scaling. The original Diet Networks concept can considerably reduce the number of parameters of the fully-connected layers by taking the transposed data matrix as an input to its auxiliary network. The efficacy of the proposed architecture was evaluated on a binary classification task for lung cancer histology, that is, adenocarcinoma or squamous cell carcinoma, from a somatic mutation profile. The dataset consisted of 950 cases, and 5-fold cross-validation was performed for evaluating the model performance. The model achieved a prediction accuracy of around 80% and showed that our modification markedly stabilized the learning process. Also, latent representations acquired inside the model allowed us to interpret the relationship between somatic mutation sites for the prediction.

Analysis of Pulmonary Microbial Diversity in Patients with Advanced Lung Cancer Based on High-throughput Sequencing Technology

背景与目的肺部微生物组与肺部疾病的发生密切相关，微生物可从多方面促进肿瘤的发生与发展。既往研究证实肺癌患者肺部微生物组较健康人发生了变化，但关于不同类型肺癌患者中肺部微生物组的微生物组成尚未明确。本研究旨在探讨不同组织学类型肺癌间的微生物组相关性及差异性。方法采用Illumina HiSeq高通量测序技术对晚期肺癌患者痰样本进行细菌V3-V4区的16S rDNA测序及生物信息学分析。结果经物种分类分析发现肺癌患者痰样本中以链球菌属、奈瑟氏菌属、普雷沃氏菌属为主。腺癌（adenocarcinoma, AD）组以链球菌属及奈瑟氏菌属为主，小细胞肺癌（small cell lung cancer, SCLC）组以奈瑟氏菌属为主，鳞状细胞癌（squamous cell carcinoma, SCC）组以链球菌属为主，混合型小细胞肺癌（combined small cell lung cancer, C-SCLC）组以链球菌属为主。结论不同组织学类型肺癌的肺部细菌微生物组结构及组成存在差异性，不同组织学类型肺癌间优势菌群有所不同，本研究丰富了肺癌肺部细菌微生物组学数据。

Lung cancer risk and residential radon exposure: A pooling of case-control studies in northwestern Spain

BackgroundThrough a pooled case-control study design, we have assessed the relationship between residential radon exposure and lung cancer risk. Other objectives of the study were to evaluate the different risk estimates for the non-small cell lung cancer histological types and to assess the effect modification of the radon exposure on lung cancer risk by tobacco consumption. MethodsWe collected individual data from various case-control studies performed in northwest Spain that investigated residential radon and lung cancer. Cases had a confirmed anatomopathological diagnosis of primary lung cancer and controls were selected because they were undergoing ambulatory evaluation or surgical procedures that were unrelated to tobacco use. Residential radon was measured using alpha track detectors. Results were analyzed using logistic regression. Results3704 participants were enrrolled, 1842 cases and 1862 controls. Data show that lung cancer risk increases with radon exposure, finding a significant association of radon exposure with lung cancer at radon exposures above 50 Bq/m3. The estimated adjusted OR for individuals exposed to concentrations >200 Bq/m3 was 2.06 (95% CI: 1.61–2.64) compared with those exposed to ≤50 Bq/m3. Within a smoking category, lung cancer risk increases markedly as radon concentration increases, reaching an OR of 29.3 (95% CI: 15.4–55.7) for heavy smokers exposed to more than 200 Bq/m.3 ConclusionsThis study confirms that residential radon exposure is a risk factor for lung cancer well below action levels established by international organizations. As expected, there is also an effect modification between radon exposure and tobacco consumption.

KRT8 and KRT19, associated with EMT, are hypomethylated and overexpressed in lung adenocarcinoma and link to unfavorable prognosis.

Background: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. To date, the prognosis of patients with LUAD remains dismal. Methods: Three datasets were downloaded from the GEO database. Differentially expressed genes (DEGs) were obtained. FunRich was used to perform pathway enrichment analysis. Protein–protein interaction (PPI) networks were established and hub genes were obtained by Cytoscape software. GEPIA was utilized to conduct correlation and survival analysis. Upstream miRNAs of DEGs were predicted via miRNet database, and methylation status of promoters of DEGs was determined through UALCAN database. Results: A total of 375 DEGs, including 105 and 270 up-regulated and down-regulated genes in LUAD, were commonly appeared in three datasets. These DEGs were significantly enriched in mesenchymal-to-epithelial transition (MET) and epithelial-to-mesenchymal transition (EMT). About 8 up-regulated and 5 down-regulated DEGs were commonly appeared in EMT/MET-related gene set and the top 50 hub gene set. Among the 13 genes, increased expression of KRT8 and KRT19 indicated unfavorable prognosis whereas high expression of DCN and CXCL12 suggested favorable prognosis in LUAD. Correlation analysis showed that KRT8 (DCN) expression was linked to KRT19 (CXCL12) expression. Further analysis displayed that KRT8 and KRT19 could jointly forecast poor prognosis in LUAD. About 42 and 2 potential miRNAs were predicted to target KRT8 and KRT19, respectively. Moreover, methylation level analysis demonstrated that KRT8 and KRT19 were significantly hypomethylated in LUAD compared with normal controls. Conclusions: All these findings suggest that KRT8 and KRT19 are hypomethylated and overexpressed in LUAD and associated with unfavorable prognosis.

Histogram Analysis of ADC Maps for Differentiating Brain Metastases From Different Histological Types of Lung Cancers.

Our study aimed to investigate the role of histogram analysis derived from apparent diffusion coefficient (ADC) maps in brain metastases (BMs) from lung cancer for differentiating histological subtype. A total of 61 BMs (45 non-small cell lung cancer [NSCLC] comprising 32 adenocarcinoma [AC], 13 squamous cell carcinoma [SCC], and 16 small-cell lung cancer [SCLC]) in 50 patients with histopathologically confirmed lung cancer were retrospectively included in this study. Pretreatment cranial diffusion-weighted imaging was performed, and the corresponding ADC maps were generated. Regions of interest were drawn on solid components of the BM on all slices of the ADC maps to obtain parameters, including ADCmax, ADCmean, ADCmin, ADCmedian, ADCrange, skewness, kurtosis, entropy, ADC10, ADC25, ADC75, and ADC90. Apparent diffusion coefficient histogram parameters were compared among histological type groups. Kruskal-Wallis, Mann-Whitney U, chi-square tests, and receiver-operating characteristic (ROC) curve were used for statistical assessment. ADCmin, ADC10, and ADC25 were found to be significantly different among AC, SCC, and SCLC groups; these parameters were higher for AC group, moderate for SCC group, and significantly lower for SCLC group. Skewness and kurtosis were not significantly different among all groups. The ROC analysis for differentiating BMs of NSCLC from SCLC showed that ADC25 achieved the highest area under the curve at 0.922 with 93.02% sensitivity and 81.25% specificity. Apparent diffusion coefficient histogram analysis of BMs from lung cancer has significant prognostic value in differentiating histological subtypes of lung cancer.

Identification of LBX2 as a novel causal gene of lung adenocarcinoma.

BackgroundLung adenocarcinoma (LUAD) is the most predominant histological type of lung cancer with a poor prognosis. In this study, we demonstrate that LBX2 regulates cell proliferation, migration and invasion and the potential molecular mechanism in LUAD.MethodsThe Cancer Genome Atlas dataset was accessed to screen for novel genes and immunohistochemistry (IHC) assays were performed to determine the association between LBX2 expression and clinicopathological features of LUAD. 5‐ethynyl‐2′‐deoxyuridine, colony formation and Real Time xCELLigence analysis system were used to evaluate the cell proliferation abilities of LUAD. Wound healing, transwell and Matrigel assays were used to detect cell migration and invasion capacities. Xenograft tumor models were used to assess the oncogenic role of LBX2 in vivo.ResultsWe found that LBX2 was hyperexpressed in LUAD and correlated with clinicopathological features and poor prognosis in LUAD patients. Knockdown of LBX2 inhibited cell proliferation, migration and invasion of LUAD, whereas ectopic expression of LBX2 enhanced tumor growth, migration, and invasion. We further found that LBX2 might participate in epithelial‐to‐mesenchymal transition (EMT) progression and influence EMT‐related gene expression.ConclusionsThe current study suggests that LBX2 plays an oncogenic role in LUAD and may participate in tumor proliferation, migration, and invasion through EMT progression.Key pointsSignificant findings of the studyLBX2 might participate in LUAD cell proliferation, migration and invasion via EMT progression.What this study adds LBX2 may represent a potential biomarker and a promising therapeutic target for LUAD.

Progress in Research on the Cribriform Component in Lung Adenocarcinoma

肺癌是全世界发病率最高的恶性肿瘤。目前，肺腺癌（lung adenocarcinoma, LUAD）是肺癌中最常见的组织学类型。然而，具有相同病理亚型的LUAD患者之间却存在显著的预后差异，导致该预后差异的主要原因之一是其组织学异质性。研究表明，除了2015年世界卫生组织（World Health Organization, WHO）对浸润性LUAD的5种主要生长方式的分类外，LUAD中还存在其他的组织学结构并影响其临床预后。其中，筛状成分（cribriform component, CC）是当前LUAD病理组织学的研究热点之一。已有研究表明，CC的有无可进一步预测LUAD患者的预后。随着相关研究逐渐深入，CC与LUAD各组织学类型、临床病理因素、生存预后等方面的关联尚存在争议。本文综合论述了CC在LUAD中的研究进展。

Patterns of Extrathoracic Metastases in Different Histological Types of Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths mainly attributable to metastasis, especially extrathoracic metastasis. This large-cohort research is aimed to explore metastatic profiles in different histological types of lung cancer, as well as to assess clinicopathological and survival significance of diverse metastatic lesions. Lung cancer cases were extracted and enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. χ2-tests were conducted to make comparisons of metastatic distribution among different histological types and odds ratios were calculated to analyze co-occurrence relationships between different metastatic lesions. Kaplan–Meier methods were performed to analyze survival outcomes according to different metastatic sites and Cox regression models were conducted to identify independent prognostic factors. In total, we included 159,241 lung cancer cases with detailed metastatic status and complete follow-up information. In order to understand their metastatic patterns, we elucidated the following points in this research: (1) Comparing the frequencies of different metastatic lesions in different histological types. The frequency of bone metastasis was highest in adenocarcinoma, squamous cell carcinoma, LCLC and NSCLC/NOS, while liver was the most common metastatic site in SCLC. (2) Elaborating the tendency of combined metastases. Bi-site metastases occurred more common than tri-site and tetra-site metastases. And several metastatic sites, such as bone and liver, intended to co-metastasize preferentially. (3) Clarifying the prognostic significance of single-site and bi-site metastases. All single-site metastases were independent prognostic factors and co-metastases ended up with even worse survival outcomes. Thus, our findings would be beneficial for research design and clinical practice.

A gene expression-based immune signature for lung adenocarcinoma prognosis.

Lung adenocarcinoma (LUAD) has become the most frequent histologic type of lung cancer in the past several decades. Recent successes with immune checkpoint blockade therapy have demonstrated that the manipulation of the immune system is a very potent treatment for LUAD. This study aims to explore the role of immune-related genes in the development of LUAD and establish a signature that can predict overall survival for LUAD patients. To identify the differential expression genes (DEGs) between normal and tumor tissues, we developed an analysis strategy to combine an independent-sample design and a paired-sample design using RNA-seq transcriptomic profiling data of The Cancer Genome Atlas LUAD samples. Further, we selected prognostic markers from DEGs and evaluated their prognostic value in a prediction model. We identified and validated PD1, PDL1 and CTLA4 genes as prognostic markers, which are well-known immune checkpoints, and revealed two new potential prognostic immune checkpoints for LUAD, HHLA2 (logFC = 2.55, FDR = 1.89 × 10-6) and VTCN1 (logFC = -2.86, FDR = 1.72 × 10-11). Furthermore, we identified an 18-gene LUAD prognostic biomarker panel and observed that the classified high-risk group presented a significantly shorter overall survival time (HR = 3.57, p value = 4.07 × 10-10). The prediction model was validated in five independent high-throughput gene expression datasets. The identified DEG features may serve as potential biomarkers for prognosis prediction of LUAD patients and immunotherapy. Based on that assumption, we identified a gene expression-based immune signature for lung adenocarcinoma prognosis.

Younger patients operated for lung cancer have a better prognosis.

BackgroundThe incidence of lung cancer in the population of patients younger than 50 years of age is relatively low. The aim of this study was to compare the clinical outcomes of patients with early lung cancer onset (ELCO, onset before the age of 50) and late lung cancer onset (LLCO, onset after the age of 50).MethodsWe have retrospectively analyzed the prospectively collected data of 1,518 patients with lung cancer treated in a Thoracic Surgery Department in the years 2007–2015. Including carcinoid tumors for the analysis may blur ELCO and LLCO population comparison; therefore we have made three analyses. We have compared overall survival (OS) in unmatched (86 patients with ELCO and 1,432 patients with LLCO) and matched the populations (with the use of propensity-score matched analysis).ResultsIn comparison of unmatched patients, five-year survival in patients with ELCO was 71.9% compared to 58.7% in LLCO patients (P=0.008). In comparison of matched populations (comparing sex, pTNM, type of operation, pathological diagnosis and Charlson Comorbidity Index) five-year survival in patients with ELCO was 77.6% comparing to 61.5% in LLCO patients P<0.001). After exclusion of rare histological types of lung cancer and advanced stages no significant difference in survival rates was discovered comparing ELCO patients with LLCO patients, although there was still a trend towards better survival in ELCO patients (P=0.086).ConclusionsPatients with ELCO have higher five-year survival after surgical treatment compared to patients with LLCO.

A Non-invasive Method to Diagnose Lung Adenocarcinoma.

Purpose: To find out the CT radiomics features of differentiating lung adenocarcinoma from another lung cancer histological type.Methods: This was a historical cohort study, three independent lung cancer cohorts included. One cohort was used to evaluate the stability of radiomics features, one cohort was used to feature selection, and the last was used to construct and evaluate classification models. The research is divided into four steps: region of interest segmentation, feature extraction, feature selection, and model building and validation. The feature selection methods included the intraclass correlation coefficient, ReliefF coefficient, and Partition-Membership filter. The performance metrics of the classification model included accuracy (Acc), precision (Pre), area under curve (AUC), and kappa statistics.Results: The 10 features (First order shape features: Sphericity and Compacity, Gray-Level Run Length Matrix: Short-Run Emphasis, Low Gray-level Run Emphasis, and High Gray-level Run Emphasis, Gray Level Co-occurrence Matrix: Homogeneity, Energy, Contrast, Correlation, and Dissimilarity) showed the most stable and classification capability. The 6 classifiers, Logistic regression classifier (LR), Sequence Minimum Optimization algorithm, Random Forest, KStar, Naive Bayes and Random Committee, have great performance both on the train and the test sets, and especially LR has the best performance on the test set (Acc = 98.72, Pre = 0.988, AUC = 1, and kappa = 0.974).Conclusion: Lung adenocarcinoma can be identified based on CT radiomics features. We can diagnose lung adenocarcinoma with CT non-invasively.

YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells

Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, and the identification of the apoptotic process of NSCLC is vital for its treatment. Usually, both the expression level and the cell surface level of TNFRSF10B (TNF Receptor superfamily member 10B) will increase after treatment with some chemotherapeutic agents, which plays a critical role in the apoptosis induction. However, the exact molecular mechanism underlying TNFRSF10B regulation remains largely elusive. Here, we found that TNFRSF10B, along with a vesicular trafficking regulator protein, YIPF2, were upregulated after treatment with pemetrexed (PEM) in NSCLC cells. Besides, YIPF2 increased the surface level of TNFRF10B, while YIPF2 knockdown inhibited the upregulation of TNFRSF10B and its recycling to plasma membrane. In addition, RAB8 decreased the cell surface TNFRSF10B by promoting its removing from plasma membrane to cytoplasm. Furthermore, we found that YIPF2, RAB8 and TNFRSF10B proteins interacted physically with each other. YIPF2 could further inhibit the physical interaction between TNFRSF10B and RAB8, thereby suppressing the removing of TNFRSF10B from plasma membrane to cytoplasm mediated by RAB8 and maintaining its high level on cell surface. Finally, using bioinformatics database, the YIPF2-TNFRSF10B axis was confirmed to be associated with the malignant progression of lung cancer. Taken together, we show that YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in NSCLC cells. These findings may be beneficial for the development of potential prognostic markers of NSCLC and may provide effective treatment strategy.

Histopathological Type of Lung Cancer and Underlying Driver Mutations in Patients with Chronic Obstructive Pulmonary Disease (COPD) versus Patients with Asthma and COPD Overlap: A Single-Center Retrospective Study.

Chronic obstructive pulmonary disease (COPD) increases the risk of lung cancer. The relationships between COPD and Asthma COPD Overlap (ACO), and between the histopathological types of lung cancer and driver mutations remain unclear and need further study. The aim of this retrospective study was to examine the relationships between the histopathological type, frequency of epidermal growth factor receptor (EGFR) driver mutations, and anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements in the lung cancers of patients with COPD and ACO. Patients with pure COPD (n=198) or ACO (n=318) who were admitted to our hospital were reviewed retrospectively. Lung cancers were identified in 43 (21.7%) patients with pure COPD and 54 (17.0%) patients with ACO. The following lung cancers types were observed: patients with pure COPD had 19 (44.2%) adenocarcinomas, 13 (30.2%) squamous cell lung carcinomas (SCC), 8 (18.6%) small cell lung carcinomas (SCLC); patients with ACO had 23 (42.6%) adenocarcinomas, 23 (42.6%) SCC, 2 (3.70%) SCLC. SCLC was significantly more prevalent in patients with pure COPD (p<0.05) than in those with ACO. Differences between the numbers of other histological types of lung cancer and the numbers of driver mutations in the 2 groups of patients were not significant. The differences in the rate of lung cancer and prevalence of EGFR driver mutations between the patients with pure COPD and those with ACO were not significant.

Non-invasive prediction of lung cancer histological types through exhaled breath analysis by UV-irradiated electronic nose and GC/QTOF/MS

Lung cancer (LC) is one of the most lethal diseases from the last decades. Accurate diagnosis of LC histology could lead to the prescription of personalized medical treatment to the affected subjects, which could reduce the mortality rate. We present here an experimental study performed in the pulmonology units of three hospitals from Morocco to non-invasively detect LC and predict LC histology via the analysis of the volatile organic compounds (VOCs) emitted through breathing. Gas chromatography coupled to a quadrupole time-of-flight mass spectrometer (GC/QTOF/MS) employed to detect the breath VOCs, revealed 30 discriminative VOCs in the breath of healthy subjects and LC patients; among them, 4 unique breath VOCs were found for the first time in the breath of LC patients, and could be used as new biomarkers for future LC diagnosis. Besides, an electronic nose (e-nose) system using a novel sensing technique in breath analysis, based on UV-irradiation of the gas sensors, was employed to characterize the overall composition of the collected breath samples, providing a satisfactory discrimination between the breath patterns of LC patients and healthy subjects. Importantly, the e-nose could further discriminate with high accuracy between the two types of LC (non-small cell LC and small cell LC), as well as between two of the major subtypes of non-small cell LC, namely squamous cell carcinoma (SCC) and adenocarcinoma (ADC). The reported results prove that breath analysis with chemical gas sensors and analytical techniques can provided an accurate mean for the non-invasive diagnosis of LC and LC histology.

ARL4C is associated with initiation and progression of lung adenocarcinoma and represents a therapeutic target.

Lung adenocarcinoma is the most common histological type of lung cancer and is classified into adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA). Atypical adenomatous hyperplasia (AAH) lesions are possible precursors to adenocarcinoma. However, the mechanism underlying the stepwise continuum of lung adenocarcinoma is unclear. In this study, the involvement of ADP‐ribosylation factor (ARF)‐like (ARL) 4C (ARL4C), a member of the small GTP‐binding protein family, in the progression of lung adenocarcinoma and the possibility of ARL4C as a molecular target for lung cancer therapy were explored. ARL4C was frequently expressed in AAH and ARL4C expression in immortalized human small airway epithelial cells promoted cell proliferation and suppressed cell death. In addition, ARL4C was expressed with increased frequency in AIS, MIA and IA in a stage‐dependent manner, and the expression was correlated with histologic grade, fluorine‐18 fluorodeoxyglucose uptake and poor prognosis. An anti–sense oligonucleotide (ASO) against ARL4C (ARL4C ASO‐1316) inhibited RAS‐related C3 botulinum toxin substrate activity and nuclear import of Yes‐associated protein and transcriptional coactivator with PDZ‐binding motif, and suppressed in vitro proliferation and migration of lung cancer cells with KRAS or epidermal growth factor receptor (EGFR) mutations. In addition, transbronchial administration of ARL4C ASO‐1316 suppressed orthotopic tumor formation induced by these cancer cells. Thus, ARL4C is involved in the initiation of the premalignant stage and is associated with the stepwise continuum of lung adenocarcinoma. ARL4C ASO‐1316 would be useful for lung adenocarcinoma patients expressing ARL4C regardless of the KRAS or EGFR mutation.

The Russian Radiobiological Human Tissue Repository: characteristics of biological specimens donated by nuclear workers with lung cancer

Purpose: Characteristics of biological specimens donated by nuclear workers with lung cancer.Materials and methods: Biological specimens were identified at the Radiobiological Human Tissue Repository (RHTR). It was established at the Southern Urals Biophysics Institute in Russia and has been developed and supported within the bilateral US-Russian Agreement on International Cooperation for Minimization of the Effects of Prolonged Radiation Exposure. Biological specimens were collected from workers of the Russian nuclear production facility Mayak PA who were exposed to gamma radiation and/or alpha particles. To determine a histologic type of lung cancer, immunohistochemistry was used.Results and conclusions: Today biological specimens donated by 343 registrants with lung cancer are available at the RHTR. Among them, 255 donors (74%) are Mayak PA workers hired at the main facilities (reactors, plutonium production, and radiochemical plants) in 1948–1982. These workers donated about 6024 specimens of lung tissues (tumor and tumor-free) stored mostly as formalin-fixed paraffin-embedded tissue blocks (31%) and histology slides (64%); in addition, they donated 1800 specimens of blood/blood components, buccal epithelium cells, and sputum. Among histologic types identified for these lung cancer cases, adenocarcinoma and small cell carcinoma were prevalent. Information about individual doses from external and internal radiation exposure, data on quantitative smoking characteristics and diseases are available for all workers with lung cancer. Complete information on radiation exposure, health status and non-radiation factors annotated to RHTR registrants and the high quality of the available biological specimens are a unique resource for studying biological mechanisms of radiation-induced lung cancer.

Residential Radon and Histological Types of Lung Cancer: A Meta-Analysis of Case‒Control Studies.

Epidemiological studies on residential radon exposure and the risk of histological types of lung cancer have yielded inconsistent results. We conducted a meta-analysis on this topic and updated previous related meta-analyses. We searched the databases of Cochrane Library, Embase, PubMed, Web of Science and Chinese National Knowledge Infrastructure for papers published up to 13 November 2018. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed and random effects models. Subgroup and dose‒response analyses were also conducted. This study was registered with PROSPERO (No. CRD42019127761). A total of 28 studies, which included 13,748 lung cancer cases and 23,112 controls, were used for this meta-analysis. The pooled OR indicated that the highest residential radon exposure was significantly associated with an increased risk of lung cancer (OR = 1.48, 95% CI = 1.26–1.73). All histological types of lung cancer were associated with residential radon. Strongest association with small-cell lung carcinoma (OR = 2.03, 95% CI = 1.52–2.71) was found, followed by adenocarcinoma (OR = 1.58, 95% CI = 1.31–1.91), other histological types (OR = 1.54, 95% CI = 1.11–2.15) and squamous cell carcinoma (OR = 1.43, 95% CI = 1.18–1.74). With increasing residential radon levels per 100 Bq/m3, the risk of lung cancer, small-cell lung carcinoma and adenocarcinoma increased by 11%, 19% and 13%, respectively. This meta-analysis provides new evidence for a potential relationship between residential radon and all histological types of lung cancer.