Reply to comment on "Plasma-derived circALG8 and circCAMTA1 as a panel for early diagnosis of non-small cell lung cancer".

Lung cancer is the leading cause of the incidence and mortality of malignant tumors in our country, seriously endangering people's lives and health. The treatment of lung cancer has made great progress in the past 10 years, and the 5-year survival rate of lung cancer in China has also increased from 16.1% to 19.7%, but about 75% of patients are still in advanced stages of lung cancer at the time of diagnosis, missing the best time for radical surgery. Early diagnosis can significantly improve the prognosis and survival of lung cancer patients. From the 5-year survival rate of lung cancer patients, it can be seen that the 5-year survival rate of stage Ⅰ patients was 77%-92%, while that of stage ⅢA-ⅣA patients was only 10%-36%, and there was a significant difference in the 5-year survival rate. Studies have shown that early-diagnosed and completely resected lung adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have 5-year disease-specific survival rates of 100% and 100%, respectively. Early diagnosis is the key to improving the prognosis of lung cancer. In order to further improve the level of early lung cancer diagnosis in China, especially the standardization in the diagnosis and evaluation of pulmonary nodules and early lung cancer, experts from the Lung Cancer Group of Chinese Thoracic Society formulated the "Chinese Expert Consensus on Diagnosis of Early Lung Cancer (2023 Edition)", on the basis of the actual situation in the field of diagnosis and treatment, with reference to the latest research data and relevant guidelines at home and abroad. Consensus on the application of artificial intelligence, big data and robotics, the Internet of Things and multidisciplinary cooperation in the diagnosis of early lung cancer, the management of pulmonary nodules and follow-up strategies for suspected early lung cancer, etc., were respectively recommended to provide references for clinicians in the diagnosis of early lung cancer, in order to further promote the early diagnosis of lung cancer in China.

Introduction: Lung cancer is the leading cause worldwide, mainly due to late diagnosis. The aim of this work was to identify a panel of epigenetic biomarkers for improving early diagnosis of lung cancer patients using minimally and non-invasive biological fluids. Patients and Methods: DNA hypermethylated biomarkers were identified performing a Genome-wide DNA methylation analysis (Infinium 450K array) in Non-small cell lung cancer (NSCLC) primary tumors from two different public databases (Discovery cohorts): CURELUNG FP7 Consortium (237 stage I NSCLC, 25 non-tumoral lung samples) and The Cancer Genome Atlas (TCGA; 350 stage I NSCLC, 62 non-tumoral lung samples). DNA methylation levels of selected candidates were analyzed by pyrosequencing in non- or minimally invasive samples from three independent cohorts of stage I NSCLC patients and non-tumoral controls (Validation cohorts): bronchoalveolar aspirates (82 NSCLC; 29 controls), bronchoalveolar lavages (51 NSCLC; 29 controls) and sputum (72 NSCLC; 26 controls). Combined Receiver Operating Characteristic (ROC) curve was obtained to evaluate the diagnostic utility of the epigenetic signature. Results: We identified a panel of 4 cancer-specific genes (BCAT1, CDO1, TRIM58 and ZNF177) with CpG island hypermethylation-associated silencing in early stage NSCLC primary tumors. All these genes presented significantly higher mean levels of%methylation (M) in NSCLC primary tumors respect to non-tumoral controls: BCAT1 (NSCLC: M>50%; Controls: M<20%), CDO1 (NSCLC: M>40%; Controls: M<10%), TRIM58 (NSCLC: M>50%; Controls: M<20%) and ZNF177 (NSCLC: M>40%; Controls : M<20%). Importantly, the diagnostic utility of the combination of this 4-gene panel signature was validated in liquid biopsy, showing a very high diagnostic accuracy with areas under the ROC curve (AUC) close to the maximum value: bronchoalveolar aspirates (AUC = 0.91; 95% CI [0.83, 0.98]; p < 0.001), bronchoalveolar lavages (AUC = 0.85; 95% CI [0.78, 0.93]; p < 0.001) and sputum (AUC = 0.93; 95% CI [0.86, 1.0]; p < 0.001). Conclusions: The herein identified DNA methylation signature could improve, in combination with current diagnostic protocols, the early diagnosis and outcome of NSCLC patients. The high diagnostic accuracy of this signature obtained in liquid biopsy offers a minimally invasive and easy accessible tool for early lung cancer diagnosis. Citation Format: A Diaz-Lagares, J Mendez-Gonzalez, D Hervas, M Saigi, MJ Pajares, D Garcia, AB Crujeiras, R Lopez-Lopez, R Pio, LM Montuenga, JJ Zulueta, E Nadal, A Rosell, M Esteller, J Sandoval. Identification of a DNA methylation signature in liquid biopsy for early non-small cell lung cancer (NSCLC) diagnosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-155.

BackgroundLung cancer is typically diagnosed at a late stage. Early presentation and detection of lung cancer symptoms is critical to improving survival but can be clinically complicated and as yet a robust screening method for diagnosis is not available in routine practice. Accordingly, the barriers to help-seeking behaviour and diagnosis need to be considered. This review aimed to document the barriers to early presentation and diagnosis of lung cancer, based on patient and carer perspectives.MethodsA systematic review of databases was performed for original, English language articles discussing qualitative research on patient perceived barriers to early presentation and diagnosis of lung cancer. Three major databases were searched: Scopus, PubMed and EBSCOhost. References cited in the selected studies were searched for further relevant articles.ResultsFourteen studies met inclusion criteria for review. Barriers were grouped into three categories: healthcare provider and system factors, patient factors and disease factors.ConclusionsStudies showed that the most frequently reported barriers to early presentation and diagnosis of lung cancer reported by patients and carers related to poor relationships between GPs and patients, a lack of access to services and care for patients, and a lack of awareness of lung cancer symptoms and treatment. Addressing these barriers offers opportunities by which rates of early diagnosis of lung cancer may be improved.

Introduction:Lung cancer (LC) is the most common cancer in the world.Well known causes are long term smoking, environmental influences and genetic variations. LC is divided into two main types based on their histological phenotypes; small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). The high specificity of these new screening methods, which are non-invasive, safe, inexpensive and simple to perform, is important in the early diagnosis and prognosis of cancer. MicroRNAs are significant biomarkers on the diagnosis metastasis and targeted therapies of NSCLC. In our study, we aimed to investigate the potential of using microRNAs as a biomarker in the early diagnosis of lung cancer.Patients and methods:Twenty patients diagnosed with lung cancer and twenty healthy individuals of the same age and gender were selected as the control group. Sixteen microRNAs were studied from blood samples.Results:Sixteen miRNAs (Let -7c, Let-7g, miR-1, miR-21, miR-29a, miR-31, miR-34a, miR 103a, miR-141, miR-155, miR-193b, miR-200b, miR-205, miR-340, miR-486, miR-708) were selected for tests and MiR 181 and miR 192 were used as the endogenous control group in line with their binding potentials and gene expression levels. The most specific and sensitive miRNAs were mirR-29a, miR-103a, and miR486 according to endogen controls in patients and healthy volunteer subjects.Discussion:A meta-analysis study showed that circulating miRNAs could be promising biomarkers for early diagnosis of lung cancer. Overall, 17 studies were included evaluating 35 miRNA markers and 19 miRNA panels in serum or plasma.Conclusion:In conclusion, there is a need for further validation studies for the use of three miRNAs as a biomarker in the early diagnosis and prognosis of lung cancer. (www.actabiomedica.it)

Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality. The clinical biomarkers currently used for the early diagnosis of lung cancer have poor sensitivity and specificity. Therefore, it is urgent to identify sensitive biomarkers for the early detection of NSCLC to improve the patient survival of patients. In our previously study, we identified glycoprotein alpha-1-antichymotrypsin (AACT) as an early biomarker of NSCLC. In this study, serum glycopeptides were enriched using the high-GlcNAc-specific binding lectin, AANL/AAL2, for further quantitative proteomics analysis using LC-MS/MS. A total of 55 differentially expressed proteins were identified by using demethylation labelling proteomics. Serum paraoxonase/arylesterase 1 (PON1) was selected for validation by western blotting and lectin-ELISA in samples from 120 enrolled patients. Our data showed that AANL-enriched PON1 has better diagnostic performance than total PON1 in early NSCLC, since it differed between early Stage I tumor samples and tumor-free samples (healthy and benign). Combining AANL-enriched PON1 with carcinoembryonic antigen (CEA) significantly improved the diagnostic specificity of CEA. Moreover, combined AANL-enriched PON1 and AANL-enriched AACT was significantly different between early NSCLC samples and tumor-free samples with an AUC of 0.940, 94.4% sensitivity, and 90.2% specificity. Our findings suggest that combined AANL-enriched PON1 and AANL-enriched AACT is a potential clinical biomarker for the early diagnosis of NSCLC.

BackgroundLung Cancer is the leading cause of cancer deaths in Aotearoa New Zealand. Māori communities in particular have higher incidence and mortality rates from Lung Cancer. Diagnosis of lung cancer at an early stage can allow for curative treatment. This project aimed to document the barriers to early diagnosis and treatment of lung cancer in secondary care for Māori communities.MethodsThis project used a kaupapa Māori approach. Nine community hui (focus groups) and nine primary healthcare provider hui were carried out in five rural localities in the Midland region. Community hui included cancer patients, whānau (families), and other community members. Healthcare provider hui comprised staff members at the local primary healthcare centre, including General Practitioners and nurses. Hui data were thematically analysed.ResultsBarriers and enablers to early diagnosis of lung cancer were categorised into two broad themes: Specialist services and treatment, and whānau journey. The barriers and enablers that participants experienced in specialist services and treatment related to access to care, engagement with specialists, communication with specialist services and cultural values and respect, whereas barriers and enablers relating to the whānau journey focused on agency and the impact on whānau.ConclusionsThe study highlighted the need to improve communication within and across healthcare services, the importance of understanding the cultural needs of patients and whānau and a health system strategy that meets these needs. Findings also demonstrated the resilience of Māori and the active efforts of whānau as carers to foster health literacy in future generations.

Lung cancer is the leading cause of death for neoplasm. Lung cancer mortality is frequently associated with late diagnosis, therefore an early diagnosis is a key factor to significantly improve overall survival in high risk populations of asymptomatic patients. Conventional cancer screenings (low-dose computed tomography or chest x-ray) today offer early detection but are invasive and expensive. Previously these studies evaluated the solid and topographic cancer structure and morphology. Today the concept of tumor has been remodelled, being defined as a disease that has its own genetic, biological and metabolic identity; it is on this new awareness that we should base new screening methods. Recent research has shown great reliability of new tests such as exhaled breath analysis, serum biomarkers and urine analysis in early diagnosis of lung cancer. Analysis of new biomarkers associated with the high specificity of these new screening methods, which are non-invasive, safe, inexpensive and simple to perform, could allow a non-invasive approach to determine a big change in the early diagnosis of cancer and its survival rate. Furthermore, these new techniques put the patient at the core of a non-invasive diagnostic process and ensure a better quality of life during medical diagnosis. In this article, we want to analyze the possible benefits of these new and promising methods, suggesting a possible combination between them to ensure, as soon as possible, an early and effective diagnosis of lung cancer with a special focus on the patient, in a new era of personalized medicine.

肺癌是世界范围内发病率和死亡率较高的恶性肿瘤之一，严重威胁着国民的生命安全与健康。肺癌的早期诊断是肺癌预防和治疗过程中的关键环节，对肺癌进行早期诊断有利于提高患者的生存率。外泌体(exosomes)与肿瘤的侵袭与转移过程密切相关，在肺癌的发生发展过程中，外泌体发挥着重要的调控作用。近年来，以外泌体为载体的生物标记物成为肺癌强有力的诊断工具。外泌体是一种由细胞分泌的由膜包裹的大小均一、直径约为30 nm-200 nm的脂质双分子层结构小囊泡。外泌体的内容物包含不同类型的核酸和蛋白质，这些核酸和蛋白质来源于其亲本细胞(包括亲本癌细胞)，具有广泛的生理功能，包括参与免疫调节、细胞间联络等。外泌体中的生物大分子物质，如单链RNA、长非编码RNA、微小RNA(microRNA, miRNA)、蛋白质以及脂类，可以为肺癌的早期临床诊断提供有价值的信息。因此，本文就外泌体的来源、结构特点、提取方法、生物学特性和在肺癌早期诊断中的作用研究进展做简要阐述。

Objective To systematically review the evidence that smoking cessation after diagnosis of a primary lung tumour affects prognosis.Design Systematic review with meta-analysis.Data sources CINAHL (from 1981), Embase (from 1980), Medline...

The objective of this research was to document the barriers to early presentation and diagnosis of lung cancer within primary healthcare, identified by Māori whānau (families) and primary healthcare providers in the Midland region of Aotearoa New Zealand. This project used a kaupapa Māori approach. Nine community hui (focus groups) and nine primary healthcare provider hui were carried out in five rural localities in the Midland region. Each community hui included cancer patients, whānau, and other community members. Each healthcare provider hui comprised staff members at the local primary healthcare centre, including General Practitioners and nurses. Hui data were thematically analysed. Barriers and enablers to early diagnosis of lung cancer were categorised into three key themes: GP relationship and position in the community, health literacy and pathways to diagnosis. This study demonstrates that culturally responsive, patient-centred healthcare, and positive GP-patient relationships are significant factors for Māori patients and whānau serving as barriers and enablers to early diagnosis of lung cancer.

The present study was undertaken to test circulating autoantibody to ATP-binding cassette C3 (ABCC3) transporter in order to confirm whether anti-ABCC3 antibody could serve as a biomarker for early diagnosis of lung cancer. This study recruited 275 patients (178 males and 97 females) with non-small cell lung cancer (either squamous carcinoma or adenocarcinoma) and 226 control subjects (134 males and 92 females) well matched in age and smoking history. Anti-ABCC3 IgA and IgG were determined using an enzyme-linked immunosorbent assay (ELISA) approach that was developed in house with the human leukocyte antigen class II (HLA-II) restricted antigens. Mann-Whitney U test showed that the IgG antibody level was significantly higher in female patients with adenocarcinoma than female controls (Z = -4.34, P < 0.001) and that the IgA antibody level was significantly higher in male patients with squamous carcinoma than male controls (Z = -3.12, P = 0.002). Pearson's Chi-square (χ(2)) test showed that female patients with adenocarcinoma had a significantly higher positive rate for IgG autoantibody than female controls (χ ( 2 ) = 8.73, P = 0.003). The ELISA sensitivity against a specificity of >95 % was 18.1 % for IgG assay in female patients and 18.0 % for IgA assay in male patients. The inter-assay deviation was 10.6 % for IgG assay and 14.5 % for IgA assay. Circulating autoantibodies to ABCC3 transporter may be a potential biomarker that can be added to a panel of existing biomarkers for early diagnosis and prognosis of lung cancer although the gender differences should be taken into account.

Objective To explore the role of multidisciplinary integrated outpatient and systematic follow-up for pulmonary nodulesin the early diagnosis and treatment of lung cancer. Methods The information about number of outpatient visit, demographics, diagnosis and suggestions at outpatient, follow-up, surgery and pathologicalfindingsof multidisciplinary integrated outpatient for pulmonary nodules during a whole year was summarized, and the role of multidisciplinary integrated outpatient for pulmonary nodules in promoting the accuracy of diagnosis of early lung cancer and rate of follow-up was investigated. Results A total of 134 patients visited multidisciplinary integrated outpatient for pulmonary nodules, and there were 261 pulmonary nodules. Early lung cancer was diagnosed in 54.5%(73/134) of patients, surgery was suggested in 41.0%(55/134) of patients, and operation was finally performed in 50 patients(37.3%). Early lung cancer before IA stage (including atypical adenomatous hyperplasia, adenocarcinoma in situ, microinvasive adenocarcinoma, and invasive pulmonary adenocarcinoma) was confirmed after operation in 33.6% of patients(45/134), and the accuracy of diagnosis of early lung cancer by multidisciplinary integrated outpatient was 90.0%(45/90). Thirty-three out of 45 patients(73.3%) with early lung cancer were diagnosed as benign pulmonary nodules in other hospitals, and were advised not to receive treatment or reexamination. Conclusions Multidisciplinary integrated outpatient and systematic follow-up for pulmonary nodules may play a role in the early diagnosis of lung cancer, and may help to reduce the related mortality of lung cancer. Key words: Pulmonary nodules; Lung cancer; Multidisciplinary integrated outpatient; Follow-up

The lack of effective means for the early diagnosis of non-small cell lung cancer (NSCLC) is the leading cause of the high mortality of NSCLC. This study aims to evaluate the clinical significance of serum mannan-binding lectin associated serine protease (MASP)-2 and isocitrate dehydrogenase 1 (IDH1) in the early diagnosis of NSCLC. The serum levels of MASP-2 and IDH1 were detected in 139 NSCLC patients, 46 patients with benign lung diseases and 61 healthy controls, using an enzyme linked immunosorbent method. The diagnostic significance in NSCLC of the two tumor markers were analyzed by receiver operating characteristic (ROC) curves. In addition, we compared the two markers with the current commonly used tumor marker cytokeratin 19 fragment (Cy¬fra21-1). The serum levels of MASP-2 and IDH1 in the NSCLC patients were significantly higher than those of healthy controls and patients with benign lung diseases. The differences were statistically significant (p < 0.01). The combined sensitivity of MASP-2, IDH1, and Cyfra21-1 in the NSCLC was 68.3%, which was significantly higher than that of the single tumor marker (p < 0.01). The sensitivities of MASP-2 and IDH1 in detecting early NSCLC (stage I and stage II) were 39.0% and 41.5%, which were significantly higher than that of Cyfra21-1 (p < 0.05). The area under the ROC curves (AUCs) of MASP-2 and IDH1 in the diagnosis of NSCLC were 0.621, and 0.840, which were higher than that of Cyfra21-1 (AUC = 0.606). Serum MASP-2 and IDH1 may be used as potential tumor markers for the auxiliary diagnosis and early diagnosis of NSCLC.

The diagnosis of lung cancer has long been a problem facing clinicians worldwide, and the emergence of electromagnetic navigation bronchoscopy (ENB) has played a critical role in the early diagnosis of lung cancer. Compared with other types of biopsy techniques (e.g., transthoracic needle biopsy, bronchoscopy, thoracoscopic biopsy, and thoracotomy), ENB guarantees high diagnostic accuracy and safety. In recent years, with the continuous development of ENB technology, the scope of its epitaxy has also expanded. This technology is no longer a simple auxiliary diagnosis test but an innovative technology that simultaneously assists in surgical treatment, opening new avenues of research for the treatment of early-stage lung cancer. However, ENB, as a human-mediated operating system, has some limitations and uncertainties in its actual clinical application and promotion, which need to be addressed as we continue to develop ENB technology. In response to the bottleneck in developing ENB technology in current clinical diagnosis and treatment, relevant scientific research and development personnel and clinicians have also performed continuing exploration and improvement of methods. However, to completely overcome the limitations of ENB, more technological innovations are needed. In this review, we describe the current major clinical application directions, application advantages, and limitations of ENB.

Early diagnosis of lung cancer is crucial for improving patient outcomes. Autoantibodies against tumor-associated antigens (TAAs) found in the plasma can serve as biomarkers for lung cancer detection. Copper transporter 1 (COPT1) is abnormally expressed in several cancers including lung cancer. The purpose of this study is to explore the significance of anti-COPT1 autoantibodies in the clinical diagnosis of non-small cell lung cancer (NSCLC). The expression level of COPT1 in NSCLC and normal tissues was analyzed based on TCGA and the Human Protein Atlas (HPA) database. Through enzyme-linked immunosorbent assay (ELISA), the expression levels of anti-COPT1 autoantibodies in plasma samples from normal controls (NC), patients with benign pulmonary nodules (BPN), and patients with NSCLC were detected in the discovery (89 NC and 89 NSCLC) and verification (321 NC, 321 BPN and 321 NSCLC) groups. The ELISA results were verified by western blotting and indirect immunofluorescence experiments. Based on HPA and TCGA databases, the mRNA and protein levels of COPT1 were higher in NSCLC tissues than in normal tissues. The levels of anti-COPT1-IgG and anti-COPT1-IgM autoantibodies were significantly higher in patients with NSCLC (P<0.05). Anti-COPT1-IgG and anti-COPT1-IgM could discriminate NSCLC from NC with area under the curve (AUC) values of 0.733 (95% CI: 0.694-0.771) and 0.679 (95% CI: 0.638-0.720), respectively. Additionally, the combination of anti-COPT1-IgG, anti-COPT1-IgM, and carcinoembryonic antigen (CEA) could enhance the efficacy of NSCLC diagnosis from BPN with increased AUC values. Our study indicated the potential significance of anti-COPT1-IgG and anti-COPT1-IgM autoantibodies as novel biomarkers for the detection of NSCLC. Furthermore, the combination of anti-COPT1-IgG and anti-COPT1-IgM improved the diagnostic value.