Histological Types Of Lung Cancer Research Articles

Effect of mesenchymal-epithelial transition amplification on immune microenvironment and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer.

BackgroundImmune checkpoint inhibitors (ICIs) have brought clinical benefits to patients with various histological types of lung cancer. Previous studies have shown an association between mesenchymal-epithelial transition (MET) and the immunotherapy response in non-small cell lung cancer (NSCLC) but there is a lack of clinical data on the correlation of MET amplification with the ICI response in NSCLC.MethodsCopy number alteration (CNA), somatic mutation, and clinical data from two immunotherapy cohorts (Rizvi et al. cohort and our local cohort) were collected and pooled to further investigate the key role of MET amplification in patients with NSCLC receiving ICIs. The correlations between MET amplification and tumor immunogenicity and antitumor immunity were further investigated in The Cancer Genome Atlas (TCGA)-NSCLC [lung adenocarcinoma (LUAD)/lung squamous cell carcinoma (LUSC)] data-set.ResultsIn the immunotherapy cohorts, MET amplification was associated with longer progression-free survival (PFS) times in patients receiving ICI treatment (P=0.039; HR =0.37; 95% CI: 0.18–0.73). In the TCGA-NSCLC data-set, MET amplification was associated with high MET mRNA and protein levels, tumor mutation burden (TMB), neoantigen load (NAL), immune-activated cell patterns, immune-related gene expression levels, and the number of gene alterations in the DNA damage response and repair (DDR) pathway. Gene set enrichment analysis (GSEA) results indicated significant up-regulation of the immune response-related pathways in the MET-amplification group.ConclusionsOur results suggest that MET amplification may be a novel predictive marker for immunotherapy efficacy in NSCLC.

The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer

The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most common histological type of lung cancer and a leading cause of cancer death worldwide. Increased phosphorylation of the translation initiation factor eIF2 (p-eIF2α), the focal point of ISR, is related to invasiveness, increased growth, and poor outcome in 928 LUAD patients. Dissection of ISR mechanisms in KRAS-driven lung tumorigenesis in mice demonstrated that p-eIF2α causes the translational repression of dual specificity phosphatase 6 (DUSP6), resulting in increased phosphorylation of the extracellular signal-regulated kinase (p-ERK). Treatments with ISR inhibitors, including a memory-enhancing drug with limited toxicity, provides a suitable therapeutic option for KRAS-driven lung cancer insofar as they substantially reduce tumor growth and prolong mouse survival. Our data provide a rationale for the implementation of ISR-based regimens in LUAD treatment.

B1 -Corrected T1 Mapping in Lung Cancer: Repeatability, Reproducibility, and Identification of Histological Types.

T1 mapping can potentially quantitatively assess the intrinsic properties of tumors. B1 correction can reduce the magnetic field inhomogeneity. To assess the repeatability and reproducibility of B1 -corrected T1 mapping for lung cancer and the ability to identify pathological types. Prospective reproducibility study. Sixty lung cancer patients (22 with emphysema) with a total of 60 lesions (adenocarcinoma [n=23], squamous cell carcinoma [n=19], and small-cell lung cancer [SCLC] [n=18]). A 3 T/B1 -corrected 3D variable flip angle T1 mapping and free-breathing diffusion-weighted imaging. Intraobserver, interobserver, and test-retest reproducibility of minimum, maximum, mean, and SD of lung tumor T1 values were assessed. The correlation between mean T1 and apparent diffusion coefficient (ADC) and differences between different histological types of lung cancer were evaluated. Intraclass correlation coefficients (ICCs), within-subject coefficients of variation (WCVs), Bland-Altman plots, Pearson's correlation coefficient (r), and analysis of variance (ANOVA). A P value <0.05 was considered to be statistically significant. No significant differences were found in minimum, maximum, mean, and SD T1 values for repeated measurements (intraobserver and interobserver) and repeated examinations (P=0.103-0.979). All parameters showed good intraobserver, interobserver and test-retest reproducibility (ICC, 0.780-0.978), except the maximum T1 value (ICC, 0.645-0.922). The mean T1 exhibited the best reproducibility and repeatability, with an average difference <6% for repeated measurements, <8% for repeated scans in lung cancer patients, and<10% for repeated scans in those with emphysema. The mean T1 correlated moderately with ADC (r=-0.580, -0.516, and -0.511 for observers A, B, and C). Both mean T1 and mean ADC were significantly different in SCLC patients compared with those in adenocarcinoma and squamous cell carcinoma patients. The mean T1 from B1 -corrected T1 mapping is a repeatable parameter with the potential to identify histological types of lung cancer and thus may be a promising imaging biomarker for characterizing lung cancer. 1 TECHNICAL EFFICACY: Stage 2.

NMU Is a Poor Prognostic Biomarker in Patients with Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most prevalent histologic type of lung cancer, associated with a high incidence rate and substantial mortality rate worldwide. Accumulating evidence shows that the aberrant expression of neuromedin U (NMU) contributes to the initiation and progression of cancer. Herein, we explored whether NMU could be adopted as a new diagnostic and therapeutic marker in LUAD. The UALCAN and GEPIA web resources were employed to assess data on the NMU expression in LUAD. The STRING web resource was used to develop the PPI (protein-protein interaction) network of NMU, whereas Cytoscape was applied for module analysis. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of NMU and the interacting proteins were examined using the WebGestalt tool. Survival analysis was performed with the Kaplan-Meier plotter tool. Results revealed that the NMU expression in LUAD was significantly higher than in the nonmalignant tissues. Moreover, higher NMU levels were dramatically related to shorter overall survival, first progression survival, and postprogression survival. The specific gene mutations G45V, R143T, and F152L of NMU occurred in LUAD samples and were associated with a worse prognosis in patients. KEGG and western blot analyses demonstrated an association of NMU with the cell cycle and the cAMP signaling cascade. Bioinformatic analysis and the in vitro experiments implicated NMU as a promising prognostic signature and treatment target for LUAD.

MiR‑200b upregulation promotes migration of BEAS‑2B cells following long‑term exposure to cigarette smoke by targeting ETS1.

Cigarette smoking is the leading cause of all histological types of lung cancer, and the role that microRNAs (miRNAs) serve in its pathogenesis is being increasingly recognized. The aim of the present study was to investigate the role of miR-200b on migration in cigarette smoke-induced malignant transformed cells. In the present study, miR-200b expression was found to be increased in cigarette smoke (CS)-exposed BEAS-2B cells, lung cancer cell lines and tumor tissue samples. Using wound healing and Transwell migration assays, the migratory ability was shown to be increased in miR-200b-overexpressing cells, whereas miR-200b knockdown resulted in reduced migration. Additionally, the expression of E-Cadherin was downregulated, whereas that of N-Cadherin was upregulated in miR-200b mimic-transfected cells, suggesting an increase in epithelial-mesenchymal transition. Downstream, using four target gene prediction tools, six target genes of miR-200b were predicted, amongst which, ETS proto-oncogene 1 transcription factor (ETS1) was shown to be significantly associated with tumor invasion depth and negatively associated with miR-200b expression. The interaction between miR-200b and ETS1 was confirmed using a dual-luciferase reporter assay. Using rescue experiments, the increased migratory ability of the miR-200b-overexpressing cells was reversed by ETS1 overexpression. In summary, this study showed that miR-200b overexpression serves a carcinogenic role and promotes the migration of BEAS-2B cells following long-term exposure to CS by targeting ETS1.

Clinical Characteristics and Molecular Profiles of Lung Cancer in Ethiopia

IntroductionLung cancer is the most common cause of cancer deaths worldwide, accounting for 1.8 million deaths each year. Only 20% of lung cancer cases are reported to occur in low- and middle-income countries. An estimated 1.5% of all Ethiopian cancers involved the lung; however, no nationwide cancer registry exists in Ethiopia. Thus, accurate data on clinical history, histopathology, molecular characteristics, and risk factors for lung cancer are not available. The aim of this study was to describe the clinical, radiologic, and pathologic characteristics, including available molecular profiles, for lung cancer at Tikur Anbessa Specialized Hospital (TASH), the main tertiary referral center in Addis Ababa, Ethiopia. MethodsA cross-sectional study was conducted at TASH among 146 patients with pathologically confirmed primary lung cancer, diagnosed from 2015 to 2019 and recorded in the Addis Ababa Cancer Registry at TASH. Clinical data were extracted from patient medical records, entered into a Research Electronic Data Capture database, and analyzed using Statistical Package for the Social Sciences statistical software. Variables collected included sociodemographics, personal exposures, comorbidities, clinical manifestations at presentation, chest imaging results, diagnostic procedures performed, histopathological classification, cancer staging, and type of treatment (if any). A subset of lung biopsies fixed in formalin for 2 to 7 days, which could be retrieved from the files of the Pathology Department of TASH, were reviewed, and molecular analysis was performed using next-generation sequencing to identify the tumor-oncogenic drivers. ResultsAmong the 146 patients studied, the mean (SD) age was 54 plus or minus 13 years; 61.6% (n = 90) were male and 25.3% (n = 37) had a history of tobacco use. The most common clinical manifestations included cough (88.4%, n = 129), chest pain (60.3%, n = 88), and dyspnea (53.4%, n = 78). The median duration of any symptoms was 6 months (interquartile range: 3–12 mo). The most common radiologic features were lung mass (84.9%, n = 129) and pleural effusion (52.7%, n = 77). Adenocarcinoma accounted for 35.7% of lung cancers (n = 52) and squamous cell carcinoma 19.2% (n = 28) from those specimens was reported. Among patients on whom staging of lung cancer was documented, 92.2% (n = 95) of the subjects presented at advanced stages (stages III and IV). EGFR mutation, exons 19 and 20, was found in 7 of 14 tissue blocks analyzed. No specific risk factors were identified, possibly reflecting the relatively small sample size and limited exposures. ConclusionsThere are marked differences in the presentation, risk factors, and molecular characteristics of lung cancer in Ethiopia as compared with other African and non-African countries. Adenocarcinoma was the most common histologic type of lung cancer detected in our study, similar to findings from other international studies. Nevertheless, compared with high-income countries, lung cancer in Ethiopia presents at a younger age, a later stage, and without considerable personal tobacco use. The relatively higher prevalence of EGFR mutation, from the limited molecular analyses, suggests that factors other than smoking history, such as exposure to biomass fuel, may be a more important risk factor. Country-specific screening guidelines and treatment protocols, in addition to a national tumor registry and greater molecular mutation analyses, are needed to improve prevention and management of lung cancer in Ethiopia.

Malayoside, a cardenolide glycoside extracted from Antiaris toxicaria Lesch, induces apoptosis in human non-small lung cancer cells via MAPK-Nur77 signaling pathway

Lung cancer is the leading cause of cancer deaths in the world. Non-small cell lung cancer (NSCLC), with poor prognosis and resistance to chemoradiotherapy, is the most common histological type of lung cancer. Therefore, it is necessary to develop new and more effective treatment strategy for NSCLC. Nur77, an orphan member of the nuclear receptor superfamily, induces apoptosis in cancer cells including NSCLC cells, by high expression and translocation to mitochondria. Small molecules trigger expression and mitochondrial localization of Nur77 may be an ideal anti-cancer drug candidate. Here, we report malayoside, a cardiac glycoside in the extract of Antiaris toxicaria Lesch., had different sensitivities to NSCLC cells. Malayoside induced apoptosis in NCI-H460 cells. Meanwhile, malayoside induced Nur77 expression and mitochondrial localization, and its induction of apoptosis was Nur77-dependent. To investigate the molecular mechanism of malayoside inducing Nur77 and apoptosis, we found that malayoside activated MAPK signaling pathway, including both ERK and p38 phosphorylation. The suppression of MAPK signaling activation inhibited the expression of Nur77 and apoptosis induced by malayoside. Our studies in nude mice showed that malayside potently inhibited the growth of tumor cells in vivo. Furthermore, the anti-cancer effect of malayosidwas in vivo was also related to the elevated expression of Nur77, p-ERK, and p-p38 proteins. Our results suggest that malayoside possesses an anti-NSCLC activity in vitro and in vivo mainly via activation of MAPK-Nur77 signaling pathway, indicating that malayoside is a promising chemotherapeutic candidate for NSCLC.

Evaluating Lung Cancer with Tumor Markers: CEA, CA 19-9 and CA 125

Aim: Lung cancer (LC) is a common and mortal malignancy. Tumor biomarkers are measurable biochemicals associated with cancer cells. Tumor markers cannot diagnose cancer; instead, they can be used as laboratory tests to support the diagnosis. In this study, we aimed to investigate the place of tumor markers in lung cancer histological types. Materials and Methods: The study included 121 stage IV lung cancer patients, 79% of whom were male, between the ages of 33-84, who were admitted to the chest diseases and thoracic surgery departments of our hospital. CEA, CA 19-9, CA 125 were studied with the immunoassay technique. Its effects on survival were investigated. LDH was analyzed for determination of tumor burden and transformation by enzymatic method. Patients were divided into groups according to the number of metastases and survival after diagnosis to evaluate clinical parameters in detail. Result: CEA in the adenocarcinoma type, CA 19-9 in the small cell subtype, CA 125 in the squamous type were significantly higher than the other histological subtypes (p = 0.037, p = 0.031, p = 0.021). CEA, CA 19-9, CA 125 values were significantly increased in patients with more than two metastases (p=0.047, p=0.039, p=0.028). When the tumor was divided into three groups as &amp;lt;3cm, 3-5cm, &amp;gt;5cm, CA 19-9 and CEA levels increased in proportion to tumor diameter, while CA 12-5 levels did not show a statistical relationship. Conclusion: CEA and CA 19-9 for adenocarcinoma type, CA 19-9 for small cell lung cancer and CA 125 for squamous cell type can help predict patients' prognosis.

肺癌による転移性骨腫瘍の組織型別の発生時期，部位，予後に関する臨床研究

肺癌による転移性骨腫瘍の組織型別の発生時期，部位，予後に関する臨床研究

Analysis of The Relationship between Blood Groups and Lung Cancer Risk Depending on Histology

Aim: Blood group antigens are the first genetic markers discovered. ABO blood groups which are expressed on red blood cell membranes are reported to be associated with malignancy risk. The present study aimed to investigate whether there is an association between blood groups and patients with lung cancer. Material and Methods: In our study, ıt was reviewed 587 patients with lung cancer whose ABO/Rh blood types were serologically confirmed. Patients were classified according to blood groups (O, A, B, AB), Rh factor (+, −) and histological types of lung cancer as Non-small cell lung carcinoma (NSCLC) and Small cell lung carcinoma (SCLC). The adenocarcinoma (AC) and squamous carcinoma (SC) as subtypes of NSCLC were recorded. The relationship of ABO/Rh blood groups with clinical features, such as age, sex and histological subtype were evaluated. Results: There was no significant association between pathological results and blood groups O, A, B and AB. SCLC patients had significantly higher frequency of blood type B Rh (-) when compared to NSCLC patients. Conclusion: We observed an association between risk of lung cancer and ABO blood groups. Although the Rh factor is not effective by itself, patients with the B Rh (-) blood group may have a higher risk than SCLC. Examining the relationship of blood group subtypes with lung cancer cells at the molecular level would be useful to clarify the relationship between lung cancer and blood groups.

Transthoracic ultrasound shear wave elastography for the study of subpleural lung lesions.

PurposeThe aim of this study was to assess whether new-generation shear wave elastography (SWE) is suitable for the characterization of lung subpleural lesions.MethodsIn total, 190 consecutive patients with subpleural lung lesions received ultrasonography and SWE. Patients with suspected malignancy underwent ultrasound-guided transthoracic needle biopsy. Final diagnoses were made on the basis of patients’ clinical course, microbiological studies, and histological results. SWE was also performed in 25 healthy volunteers.ResultsWe found no statistically significant differences in stiffness between lung carcinomas, lung metastases, and pneumonia (P=0.296) or between different histological types of lung cancer (P=0.393). Necrosis was associated with reduced stiffness in pneumonia. Excluding necrotic lesions, pneumonia showed higher stiffness than lung carcinomas (2.95±0.68 m/s vs. 2.60±0.54 m/s, P=0.006). Chronic pneumonia showed increased stiffness (3.03±0.63 m/s), probably due to the presence of fibrotic tissue on histology. Pleural effusion was associated with a statistically significant reduction in stiffness, both in lung carcinomas (P=0.004) and lung metastases (P=0.002). The presence of air in healthy lung tissue may lead to incorrect speed estimates due to shear wave reflection (very high values, 14.64±2.19 m/s).ConclusionTransthoracic SWE could not distinguish lung malignancy from pneumonia, or between different histological types of lung carcinomas. In particular, SWE seems unable to resolve the clinical dilemma of chronic subpleural consolidations.

A deep learning model for the classification of indeterminate lung carcinoma in biopsy whole slide images

The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hematoxylin and Eosin (H&E)-stained slides of small transbronchial lung biopsy (TBLB) are one of the primary sources for making a diagnosis; however, a subset of cases present a challenge for pathologists to diagnose from H&E-stained slides alone, and these either require further immunohistochemistry or are deferred to surgical resection for definitive diagnosis. We trained a deep learning model to classify H&E-stained Whole Slide Images of TBLB specimens into ADC, SCC, SCLC, and non-neoplastic using a training set of 579 WSIs. The trained model was capable of classifying an independent test set of 83 challenging indeterminate cases with a receiver operator curve area under the curve (AUC) of 0.99. We further evaluated the model on four independent test sets—one TBLB and three surgical, with combined total of 2407 WSIs—demonstrating highly promising results with AUCs ranging from 0.94 to 0.99.

34P Sex and age differences in primary lung cancer in Morocco: An epidemiologic study

Background: Lung cancer is a leading cause of death worldwide. In Morocco, it is the most commonly occurring cancer in men. The aim of this study is to determine the epidemiological and histological profile of primary lung cancer in Rabat (capital of Morocco) over a 4-year period, from 2014 to 2017, by sex and age. Methods: This is a descriptive retrospective study of all patients with primary lung cancer diagnosed and treated at Ibn Sina University Hospital Center in Rabat during the period from January 2014 to December 2017. The data were collected from medical records for each patient. Statistical analysis was performed using Epi InfoTM7. Results: During the period of study, 574 new cases of primary lung cancer were diagnosed. Of these, 87.5% were men and 12.5% were women, giving a male-female ratio of 7. The average age of patients at diagnosis was 58.4 years (range 21–85 years). There was no significant gender difference in average age. The age distribution show that 19.9% of patients were aged less than 50 years, 29.7% were in the 50–59-year age group, 33.8% were aged between 60 and 69 years and 16.5% were aged 70 years and older. According to the results, 7.3% of lung cancers were small cell lung cancer (SCLC) and 90.9% were non-small cell lung cancer (NSCLC). Adenocarcinoma was the most frequent cell type of lung cancer, with 60.45%, followed by squamous cell carcinoma, with 23%. According to gender, adenocarcinoma was more common in women (70.8%) than in men (58.4%), while squamous cell carcinoma was relatively frequent in men (24.7%) than in women (11.1%). There was no significant difference in age of diagnosis, by histological type of lung cancer. Conclusions: Lung cancer is a serious and potentially deadly disease in Morocco. It is important to develop strategies that take into account the current trends in lung cancer and target particularly groups at risk. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

A Study of Patient Preferences for the Treatment of Non–small Cell Lung Cancer in Western China: A Discrete-Choice Experiment

Background: Non–small cell lung cancer (NSCLC) is the most common histologic type of lung cancer, accounting for 70–85% of all lung cancers. It has brought a heavy burden of disease and financial cost to families, society, and the nation of China. Patients have differing preferences for treatment because of their varying physical conditions and socioeconomic backgrounds, which ultimately affects the choice of treatment as well as treatment outcomes. For better and sustained health outcomes, it is vital to understand patients' preferences. We can then provide medical services to match these preferences and needs rather than basing treatment on our clinical viewpoints alone.Objectives: The aim of this study was to elicit patient preferences for treatment using a discrete-choice experiment and to explore the value/importance that patients place on the different attributes of treatment in order to provide a basis for clinical decision making and patient health management.Methods: The study was conducted with NSCLC patients from three typical hospitals in southwestern China. After identifying patient-relevant treatment attributes via literature review and qualitative semi structured interviews, a discrete-choice experiment (DCE) including seven patient-relevant attributes was conducted using a fractional factorial SAS design. The empiric data analyses of patients were performed using mixed logit models.Results: NSCLC patients (N = 202) completed a survey via a face-to-face interview. Among the seven attributes, the following were considered important: progression-free survival, disease control rate, cost, weakness/fatigue, and nausea/vomiting; mode of administration and rash were considered less important. A clear preference for an increase in progression-free survival and disease control rate was demonstrated. Compared with 5 months of progression-free survival, respondents were willing to pay more (19,860 RMB) for 11 months of progression-free survival (coef.: 0.687). Compared with a 60% rate of disease control, respondents were willing to pay more (19,940 RMB) for a 90% rate of disease control (coef.: 0.690).Conclusions: This study demonstrates the value of DCEs in determining patient preferences for the treatment of NSCLC. The results indicate that not only efficacy factors (such as progression-free survival and disease control rate) were considered but also other factors (such as side effects and treatment costs) and trade-offs between attributes were held to be important. These results are in accord with expectations and can provide evidence for more effective and efficient treatment results. Furthermore, the current results can increase benefits if the presented therapies can be designed, assessed, and chosen based on patient-oriented findings.

FAM201A knockdown inhibits proliferation and invasion of lung adenocarcinoma cells by regulating miR-7515/GLO1 axis.

Lung adenocarcinoma (LUAD) is the most important histological type of lung cancer. We aimed to identify the role of long noncoding RNA family with sequence similarity 201-member A (FAM201A) in the occurrence and development of LUAD. The expressions of FAM201A in LUAD tissues and cells were determined via reverse transcription-quantitative polymerase chain reaction. The effects of FAM201A knockdown on LUAD cell malignant phenotypes were examined by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell assay and wound healing assay. The underlying mechanism by which FAM201A regulated LUAD progression was also studied. Nude mice LUAD xenograft model was constructed, to explore the in vivo effect of FAM201A. Our results showed that the FAM201A expression in LUAD tissues and cell lines was notably higher than normal tissues and cells. Downregulation of FAM201A suppressed the cell proliferation, migration and invasion and promoted the cell apoptosis in LUAD cells. While, FAM201A overexpression showed tumorigenesis effect on LUAD cells. Moreover, we demonstrated that FAM201A affected LUAD progression via targeting miR-7515 to promote GLO1 expression. FAM201A downregulation also suppressed LUAD development in vivo experiment. Our results indicated that FAM201A was an oncogene in LUAD and might be a novel therapeutic target for LUAD.

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.

PL01.06 Molecular Epidemiology of Asian Lung Cancer

Lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, develops in both ever- and never-smokers, and has two distinct characteristics in Asian populations. First, the proportion of never-smoking patients is considerably higher than that among individuals of European descent (approximately 40% vs 10%), and the rates of development and death from lung cancer in never-smokers are significantly higher in Asians than those in individuals of European descent. Second, in Asian individuals LADC frequently (in approximately 50% of cases) carries oncogenic mutations of the epidermal growth factor receptor (EGFR) gene, in contrast to lower EGFR mutation rates (approximately 10%) in European/US patients. In Asian patients, EGFR mutation frequently occurs in both never- (60%) and ever- (40%) smokers, while it occurs almost exclusively in European/US ever-smokers. Notably, EGFR-mutated LADC does not respond well to immune checkpoint blockade therapy due to its non-inflamed (immune-cold) features, including low infiltration of CD4+ and CD8+ T cells. Therefore, it is highly likely that there are specific risk factors, independent from smoking, that promote LADC development in Asians and have immunogenic effects influencing tumour characteristics. By conducting genome-wide association study, we demonstrated that HLA loci influence lung adenocarcinoma risk independently from smoking and that the association of HLA-class II, but not class I, loci is more prominent for lung adenocarcinomas with EGFR gene mutations than those without; the HLA-DPB1 Asp57 and 76Val alleles are associated with elevated risk for EGFR-mutated lung adenocarcinoma. HLA variants might influence lung adenocarcinoma risk by modulating anti-tumour immunity.

Vascular patterns on narrow band imaging (NBI) video bronchoscopy of lung cancer patients and its relationship with histology: an analytical cross-sectional study.

Narrow band imaging (NBI) video bronchoscopy provides better visualisation of submucosal vascular patterns in malignant airway lesions compared to white light bronchoscopy. This analytical cross-sectional study was aimed to look for any relationship between these NBI vascular patterns and the histologic type of lung cancer. After screening 78 patients with suspected lung cancer, 53 subjects underwent video bronchoscopy. Thirty-two patients showing abnormal bronchial mucosa or endobronchial growth with any of the NBI vascular patterns on bronchoscopy were enrolled in the study. These abnormal areas were then biopsied and sent for histologic examination. NBI bronchoscopy revealed a dilated tortuous vascular pattern in 54.8% of the patients, a non-specific pattern in 32%, a dotted pattern in 9.7% and an abrupt ending vessels pattern in 3.2% of the patients. We did not find any statistically significant relationship between a dilated tortuous pattern and squamous-cell carcinoma (p = 0.48), adenocarcinoma (p = 0.667) or small-cell carcinoma (p = 1); between a dotted pattern and squamous-cell carcinoma (p = 1), adenocarcinoma (p = 0.54) or small-cell carcinoma (p = 1), and between an abrupt ending capillary pattern and squamous-cell carcinoma (p = 1), adenocarcinoma (p = 1) or small-cell carcinoma (p =1). No relationship exists between NBI vascular patterns and the histology of lung cancer. Endobronchial lesions showing any vascular pattern on NBI needs to be adequately sampled for proper histologic and molecular studies in lung cancer patients.

Identification of KIF4A and its effect on the progression of lung adenocarcinoma based on the bioinformatics analysis.

Background: Lung adenocarcinoma (LUAD) is the most frequent histological type of lung cancer, and its incidence has displayed an upward trend in recent years. Nevertheless, little is known regarding effective biomarkers for LUAD.Methods: The robust rank aggregation method was used to mine differentially expressed genes (DEGs) from the gene expression omnibus (GEO) datasets. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to extract hub genes from the protein–protein interaction (PPI) network. The expression of the hub genes was validated using expression profiles from TCGA and Oncomine databases and was verified by real-time quantitative PCR (qRT-PCR). The module and survival analyses of the hub genes were determined using Cytoscape and Kaplan–Meier curves. The function of KIF4A as a hub gene was investigated in LUAD cell lines.Results: The PPI analysis identified seven DEGs including BIRC5, DLGAP5, CENPF, KIF4A, TOP2A, AURKA, and CCNA2, which were significantly upregulated in Oncomine and TCGA LUAD datasets, and were verified by qRT-PCR in our clinical samples. We determined the overall and disease-free survival analysis of the seven hub genes using GEPIA. We further found that CENPF, DLGAP5, and KIF4A expressions were positively correlated with clinical stage. In LUAD cell lines, proliferation and migration were inhibited and apoptosis was promoted by knocking down KIF4A expression.Conclusion: We have identified new DEGs and functional pathways involved in LUAD. KIF4A, as a hub gene, promoted the progression of LUAD and might represent a potential therapeutic target for molecular cancer therapy.

Synthetic CT image generation of shape-controlled lung cancer using semi-conditional InfoGAN and its applicability for type classification.

In recent years, convolutional neural network (CNN), an artificial intelligence technology with superior image recognition, has become increasingly popular and frequently used for classification tasks in medical imaging. However, the amount of labelled data available for classifying medical images is often significantly less than that of natural images, and the handling of rare diseases is often challenging. To overcome these problems, data augmentation has been performed using generative adversarial networks (GANs). However, conventional GAN cannot effectively handle the various shapes of tumours because it randomly generates images. In this study, we introduced semi-conditional InfoGAN, which enables some labels to be added to InfoGAN, for the generation of shape-controlled tumour images. InfoGAN is a derived model of GAN, and it can represent object features in images without any label. Chest computed tomography images of 66 patients diagnosed with three histological types of lung cancer (adenocarcinoma, squamous cell carcinoma, and small cell lung cancer) were used for analysis. To investigate the applicability of the generated images, we classified the histological types of lung cancer using a CNN that was pre-trained with the generated images. As a result of the training, InfoGAN was possible to generate images that controlled the diameters of each lesion and the presence or absence of the chest wall. The classification accuracy of the pre-trained CNN was 57.7%, which was higher than that of the CNN trained only with real images (34.2%), thereby suggesting the potential of image generation. The applicability of semi-conditional InfoGAN for feature learning and representation in medical images was demonstrated in this study. InfoGAN can perform constant feature learning and generate images with a variety of shapes using a small dataset.