Estandarización de requerimientos mínimos para la formación de centro de detección temprana de cáncer de pulmón en América Latina / Standardization of Minimum Requirements for the Formation of an Early Detection Center for Lung Cancer in Latin America

Introducción: El cáncer de pulmón (CP) es una enfermedad con gran impacto a nivel mundial en el número de muertes y en costos en salud. La alta incidencia y mortalidad de esta enfermedad asociada al diagnóstico tardío, y la mejoría del pronóstico ante una detección temprana, determinan que sea una patología pasible de beneficiarse mediante detección temprana. La tomografía de baja dosis de radiación (TCBD) demostró ser un método que se pue- de realizar periódicamente a un grupo de personas con alto riesgo de desarrollar CP y así reducir la mortalidad por esta enfermedad. Sin embargo, este beneficio es tal cuan- do se encuentra desarrollado bajo un programa organizado y con participación multi- disciplinaria especializada en cáncer de pulmón. Métodos: Se plantea determinar lineamientos básicos para el desarrollo de la detección temprana de cáncer de pulmón en América Latina para que pueda ser realizada en forma uniforme, con el menor riesgo y el máximo beneficio esperado. Se analizaron las principales publicaciones referidas a este tema, contemplando la diversidad de atención y acceso de América Latina. Resultado: Se desarrollan requerimientos mínimos para la implementación de un pro- grama. Discusión: El número de programas en la región es escaso y depende más de esfuerzos individuales que de políticas generales de salud. Consideramos que estos lineamien- tos pueden servir de apoyo para el desarrollo de más programas en la región y de for- ma más homogénea.

Introduction: Lung cancer (LC) is a disease with a great impact worldwide in the number of deaths and health costs. The high incidence and mortality of this disease associated with late diagnosis and the improved prognosis with early detection determine that it is a pathology that can benefit from early detection. Low radiation dose tomography (LDCT) demonstrated a method that can be performed periodically to a group of people at high risk of developing CP and thus reduce mortality from this disease. However, this benefit is such when it is developed under an organized program with multidisciplinary participation specialized in lung cancer. Methods: It is proposed to determine basic guidelines for the development of early de- tection of lung cancer in Latin America so that it can be carried out uniformly, with the lowest risk and the maximum expected benefit. The main publications referring to this topic were analyzed, considering the diversity of care and access in Latin America. Result: Minimum requirements are developed for the implementation of a program. Discussion: The number of programs in the region is small and depends more on individual efforts than on general health policies. We consider that these guidelines can serve as support for the development of more programs in the region and in a more ho- mogeneous way.

Identificación de las características de los ganglios evaluados en el procedimiento EBUS y su relación con el diagnóstico de malignidad en instituto de alta complejidad en cáncer / Identification of the Characteristics of the Lymph Nodes Evaluated in the EBUS Procedure and their Relationship with the Diagnosis of Malignancy in a Highly Complex Cancer Institute

Introducción: La EBUS ha sido el foco de numerosos estudios destinados a evaluar su utilidad y rendimiento diagnóstico en diversas patologías. Objetivo principal: Identificación de las características ganglionares evaluadas en el procedimiento de Ultrasonido Endobronquial (EBUS) y su relación con el diagnóstico de malignidad en pacientes del Instituto Nacional del Cáncer de Colombia del 1 de enero de 2017 al 31 de marzo de 2021.Métodos: Estudio analítico observacional transversal. La recopilación de datos implicó un muestreo de casos consecutivos no probabilísticos entre individuos que cumplían los criterios de inclusión.Resultados: Un total de 75 pacientes fueron sometidos a EBUS. Se identificaron 6 características ecográficas de los ganglios de la biopsia asociadas a malignidad destacándose los ganglios mayores de 1 cm, márgenes mal definidos, ecogenicidad heterogénea, ausencia de una estructura hiliar central, presencia de signos de necrosis o coagulación y presencia de conglomerado ganglionar. Conclusión: Este estudio caracterizó la frecuencia de los hallazgos en la ultrasonografía endobronquial destacando algunas características ecográficas de los ganglios mediastínicos que podrían predecir patología maligna.

Introduction: The EBUS has been the focus of numerous studies aiming to evaluate its utility and diagnostic performance across various pathologies. Objective: Identification of the node characteristics evaluated in the Endobronchial Ultrasound (EBUS) procedure and their relationship with malignancy diagnosis in patients at the National Cancer Institute of Colombia from January 1st, 2017, to March 31st, 2021. Methods: Observational cross-sectional analytical study. Data collection involved non-probabilistic consecutive case sampling among individuals meeting the inclusion criteria.Results: A total of 75 patients underwent the EBUS procedure. Our findings revealed six predictors of malignancy based on sonographic features of biopsy nodes, including nodes larger than 1 cm, poorly defined margins, heterogeneous echogenicity, absence of a central hilar structure, presence of signs indicating necrosis or coagulation, and the presence of a ganglion conglomerate. Conclusions: This study showed that endobronchial ultrasonography has several sonographic characteristics at the time of evaluating mediastinal nodes that could predict malignant and benign pathology.

Smoking, mortality, access to diagnosis, and treatment of lung cancer in Brazil / Tabagismo, mortalidade, acesso ao diagnóstico e tratamento de câncer de pulmão no Brasil

ABSTRACT INTRODUCTION Lung cancer (LC) is a relevant public health problem in Brazil and worldwide, given its high incidence and mortality. Thus, the objective of this study is to analyze the distribution of smoking and smoking status according to sociodemographic characteristics and disparities in access, treatment, and mortality due to LC in Brazil in 2013 and 2019. METHOD Retrospective study of triangulation of national data sources: a) analysis of the distribution of smoking, based on the National Survey of Health (PNS); b) investigation of LC records via Hospital-based Cancer Registry (HCR); and c) distribution of mortality due to LC in the Mortality Information System (SIM). RESULTS There was a decrease in the percentage of people who had never smoked from 2013 (68.5%) to 2019 (60.2%) and in smoking history (pack-years). This was observed to be greater in men, people of older age groups, and those with less education. Concerning patients registered in the HCR, entry into the healthcare service occurs at the age of 50, and only 19% have never smoked. While smokers in the population are mainly Mixed-race, patients in the HCR are primarily White. As for the initial stage (I and II), it is more common in White people and people who have never smoked. The mortality rate varied from 1.00 for people with higher education to 3.36 for people without education. Furthermore, White people have a mortality rate three times higher than that of Black and mixed-race people. CONCLUSION This article highlighted relevant sociodemographic disparities in access to LC diagnosis, treatment, and mortality. Therefore, the recommendation is to strengthen the Population-Based Cancer Registry and develop and implement a nationwide LC screening strategy in Brazil since combined prevention and early diagnosis strategies work better in controlling mortality from the disease and continued investment in tobacco prevention and control policies.

RESUMO INTRODUÇÃO O câncer de pulmão (CP) é um relevante problema de saúde pública no Brasil e no mundo, dada sua alta incidência e mortalidade. Assim, objetiva-se analisar a distribuição do tabagismo e da carga tabágica segundo características sociodemográficas e disparidades no acesso, no tratamento e na mortalidade por CP no Brasil, em 2013 e 2019. MÉTODO Estudo retrospectivo de triangulação de fontes de dados de abrangência nacional: a) análise da distribuição do tabagismo, baseada na Pesquisa Nacional de Saúde (PNS); b) investigação dos registros de CP, via Registros Hospitalares de Câncer (RHC); e c) distribuição da mortalidade por CP, no Sistema de Informação sobre Mortalidade (SIM). RESULTADOS Verificou-se redução do percentual de pessoas que nunca fumaram de 2013 (68,5%) para 2019 (60,2%), assim como da carga tabágica (anos-maço). Esta foi observada maior em homens em pessoas de faixas etárias mais avançadas e de menor escolaridade. Em relação aos pacientes registrados no RHC, a entrada no serviço de saúde se dá a partir de 50 anos, e apenas 19% nunca fumaram. Ao passo que os fumantes na população são majoritariamente pardos, os pacientes no RHC são em maioria brancos. Quanto ao estadiamento inicial (I e II), é mais frequente em pessoas brancas e que nunca fumaram. A taxa de mortalidade apresentou variação de 1,00, para pessoas com ensino superior, a 3,36, entre pessoas sem instrução, assim como pessoas brancas têm uma taxa de mortalidade três vezes maior que a de pessoas negras e pardas. CONCLUSÃO Este artigo apontou relevantes disparidades sociodemográficas no acesso ao diagnóstico, tratamento e mortalidade do CP. Assim, recomenda-se: fortalecer o Registro de Câncer de Base Populacional; desenvolver e implementar estratégia de screening de CP no Brasil, uma vez que a realização de estratégias de prevenção e diagnóstico precoce combinadas funcionam melhor no controle da mortalidade pela doença; e investimento contínuo nas políticas de prevenção e controle do tabagismo.

Molecular classification of small cell lung cancer subtypes: Characteristics, prognostic factors, and clinical translation / 中华医学杂志(英文版)

Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

Expert consensus on diagnosis and treatment of malignant pleural effusion caused by lung cancer / 中华肿瘤杂志

Malignant pleural effusion (MPE) can occur in nearly all types of malignant tumors, with lung cancer being the most prevalent cause. The presence of MPE indicates an advanced stage or distant spread of the tumor, significantly reducing the patient's life expectancy. Particularly, a substantial amount of pleural effusion can impede heart and lung function, impair blood oxygen perfusion levels in the body, and greatly diminish patients' quality of life. Even when systemic treatment has alleviated the primary lung tumor in some patients, effective control over MPE remains challenging and impacts clinical outcomes. Therefore, it is crucial to implement measures for reducing or managing MPE while ensuring standardized treatment for lung cancer. In recent years, significant advancements have been made in diagnosing and treating lung cancer complicated by MPE through extensive basic and clinical research. Based on existing evidence and China's clinical practice experience, relevant experts from the China Association of Health Promotion and Education and Cancer Rehabilitation and Palliative Treatment Professional Committee of China Anti-Cancer Association (CRPC) have summarized key aspects related to diagnosis and treatment consensus opinions for lung cancer complicated by MPE. This aims to establish standardized procedures that will serve as a reference for doctors' clinical practice.

Progress of BRAF Gene Alteration in Non-small Cell Lung Cancer / 中国肺癌杂志

V-Raf murine sarcoma viral oncogene homolog B (BRAF) alteration is one of the most essential driver genes of non-small cell lung cancer (NSCLC). BRAF encodes serine/threonine protein kinases, and its mutations typically lead to protein compositional activation, thereby activating the mitogen-activated protein kinase kinase (MEK) signaling pathway. A promising new approach for the treatment of mutated BRAF and/or downstream MEK may provide customized treatment opportunities for BRAF driven NSCLC patients. However, combination therapy is necessary to overcome the difficulties such as short duration of benefit, poor therapeutic effect of non-V600 BRAF mutations and susceptibility to drug resistance. This article reviewed the progress in structural characteristics, related signaling pathways, mutation types of BRAF gene, and the clinical pathological relationship between BRAF mutations and NSCLC, as well as the therapy, in order to provide more evidences for clinical doctors to make treatment decisions.
.

Research Progress of Granulocytic Myeloid-derived Suppressor Cells in Non-small Cell Lung Cancer / 中国肺癌杂志

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.
.

Establishment of a 21-color Panel for the Detection of Immune Cell Subsets in Human Non-small Cell Lung Cancer Tumor Tissues with Flow Cytometry / 中国肺癌杂志

BACKGROUND@#With the rise of multicolor flow cytometry, flow cytometry has become an important means to detect the immune microenvironment of lung cancer, but most of them are used to detect the proportion of cell subsets or the function of major cell subsets, and they cannot be detected at the same time. Therefore, a reliable 21-color flow cytometry protocol was established to detect the immune cell subsets in human non-small cell lung cancer (NSCLC) tumor tissues.@*METHODS@#Cell membrane surface antibodies cluster of differentiation (CD)45, CD3, CD19, CD4, CD8, programmed cell death 1 (PD-1), CD39, CD103, CD25, CD127, chemokine receptor 8 (CCR8), CD56, CD11c, human leukocyte antigen (HLA)-DR, CD38, CD27, CD69, CD62L, CD45RA, CCR7 and nucleic acid dye L/D were used to develop the protocol. Firstly, antibody titration experiments, voltage optimization, subtraction of one color staining and single color staining experiments were carried out for each antibody, and after the experimental conditions and detection schemes were determined, the feasibility of the scheme was verified by using peripheral blood mononuclear cells (PBMCs) specimens of six healthy adult volunteers. Tumor tissue samples from 6 NSCLC patients were tested and analyzed.@*RESULTS@#The established 21-color flow cytometry protocol was used to detect the tumor tissue samples of 6 NSCLC patients, and the proportion of each cell subset in lung cancer tissue, as well as the immunophenotype and differentiation of the main cell population, were analyzed.@*CONCLUSIONS@#The successfully established 21-color flow cytometry protocol is suitable for the detection of PBMCs and NSCLC tissue samples, which provides an effective new idea for monitoring the immune microenvironment status in lung cancer.

Construction of a Prognostic Prediction Model of Patients with Pathologic N0 in Resected Invasive Mucinous Adenocarcinoma of the Lung / 中国肺癌杂志

BACKGROUND@#Invasive mucinous adenocarcinoma (IMA) was a rare and specific type of lung adenocarcinoma, which was often characterized by fewer lymphatic metastases. Therefore, it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis (TNM) staging. So, this study aimed to develop Nomograms to predict outcomes of patients with pathologic N0 in resected IMA.@*METHODS@#According to the inclusion criteria and exclusion criteria, IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University (training cohort, n=78) and Ningbo No.2 Hospital (validation cohort, n=66) were reviewed between July 2012 and May 2017. The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established, and the performances of models were evaluated. Finally, the validation cohort data was put in for external validation.@*RESULTS@#Univariate analysis showed that pneumonic type, larger tumor size, mixed mucinous/non-mucinous component, and higher overall stage were significant influence factors of 5-year progression-free survival (PFS) and overall survival (OS). Multivariate analysis further indicated that type of imaging, tumor size, mucinous component were the independent prognostic factors for poor 5-year PFS and OS. Moreover, the 5-year PFS and OS rates were 62.82% and 75.64%, respectively. In subgroups, the survival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients, respectively. The C-index of Nomograms with 5-year PFS and OS were 0.815 (95%CI: 0.741-0.889) and 0.767 (95%CI: 0.669-0.865). The calibration curve and decision curve analysis (DCA) of both models showed good predictive performances in both cohorts.@*CONCLUSIONS@#The Nomograms based on clinicopathological characteristics in a certain extent, can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.

Establishment of a Predictive Model for Chronic Cough after Pulmonary Resection / 中国肺癌杂志

BACKGROUND@#Chronic cough after pulmonary resection is one of the most common complications, which seriously affects the quality of life of patients after surgery. Therefore, the aim of this study is to explore the risk factors of chronic cough after pulmonary resection and construct a prediction model.@*METHODS@#The clinical data and postoperative cough of 499 patients who underwent pneumonectomy or pulmonary resection in The First Affiliated Hospital of University of Science and Technology of China from January 2021 to June 2023 were retrospectively analyzed. The patients were randomly divided into training set (n=348) and validation set (n=151) according to the principle of 7:3 randomization. According to whether the patients in the training set had chronic cough after surgery, they were divided into cough group and non-cough group. The Mandarin Chinese version of Leicester cough questionnare (LCQ-MC) was used to assess the severity of cough and its impact on patients' quality of life before and after surgery. The visual analog scale (VAS) and the self-designed numerical rating scale (NRS) were used to evaluate the postoperative chronic cough. Univariate and multivariate Logistic regression analysis were used to analyze the independent risk factors and construct a model. Receiver operator characteristic (ROC) curve was used to evaluate the discrimination of the model, and calibration curve was used to evaluate the consistency of the model. The clinical application value of the model was evaluated by decision curve analysis (DCA).@*RESULTS@#Multivariate Logistic analysis screened out that preoperative forced expiratory volume in the first second/forced vital capacity (FEV1/FVC), surgical procedure, upper mediastinal lymph node dissection, subcarinal lymph node dissection, and postoperative closed thoracic drainage time were independent risk factors for postoperative chronic cough. Based on the results of multivariate analysis, a Nomogram prediction model was constructed. The area under the ROC curve was 0.954 (95%CI: 0.930-0.978), and the cut-off value corresponding to the maximum Youden index was 0.171, with a sensitivity of 94.7% and a specificity of 86.6%. With a Bootstrap sample of 1000 times, the predicted risk of chronic cough after pulmonary resection by the calibration curve was highly consistent with the actual risk. DCA showed that when the preprobability of the prediction model probability was between 0.1 and 0.9, patients showed a positive net benefit.@*CONCLUSIONS@#Chronic cough after pulmonary resection seriously affects the quality of life of patients. The visual presentation form of the Nomogram is helpful to accurately predict chronic cough after pulmonary resection and provide support for clinical decision-making.

Identification and Analysis of SND1 as an Oncogene and Prognostic Biomarker for Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD.@*METHODS@#Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed.@*RESULTS@#SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1.@*CONCLUSIONS@#SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

Effectiveness Evaluation of Low-dose Spiral Computed Tomography for Lung Cancer Screening in Minhang District of Shanghai / 中国肺癌杂志

BACKGROUND@#Low-dose spiral computed tomography (LDCT) has been recommended for lung cancer screening in high-risk populations. However, evidence from Chinese populations was limited due to the different criteria for high-risk populations and the short-term follow-up period. This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013.@*METHODS@#A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017. Results of LDCT examination, and screen-detected cancer cases in all participants were obtained from the Reporting System of the Lung Cancer Screening Program. The newly-diagnosed cases and their vital status up to December 31, 2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics. Standardized incidence ratio (SIR) and 95%CI were calculated using the local population at ages of 40 or above as the reference. Proportions of early-stage cancer (stage 0-I), pathological types, and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations. Cox regression models were applied to evaluate the hazard ratio (HR) and 95%CI of LDCT screening with all-cause death of the lung cancer cases.@*RESULTS@#The crude and age-standardized incidence of lung cancer in screened population were 373.3 (95%CI: 343.1-406.1) and 70.3 per 100,000 person-years, respectively, with an SIR of 1.8 (95%CI: 1.6-1.9), which was observed to decrease with following-up time. The early-stage cancer accounted for 49.4% of all lung cancer cases derived from the screened population, significantly higher than 38.4% in cases from the non-screened population during the same period (P<0.05). The proportion of lung adenocarcinoma (40.7% vs 35.9%) and 5-year survival rate (53.7% vs 41.5%) were also significantly higher in the cases from the screened population (all P<0.05). LDCT screening was associated with 30% (HR=0.7, 95%CI: 0.6-0.8) reduced all-cause deaths of the cases.@*CONCLUSIONS@#The participants of the screening program are at high-risk of lung cancer. LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases, indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations.

TRIP13 Enhances Radioresistance of Lung Adenocarcinoma Cells through the Homologous Recombination Pathway / 中国肺癌杂志

BACKGROUND@#Radiation therapy is one of the most common treatments for non-small cell lung cancer (NSCLC). However, the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients, and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge. This study aimed to identify the molecules associated with radioresistance in lung adenocarcinoma (LUAD), identified thyroid hormone receptor interactor 13 (TRIP13) as the main target initially, and explored whether TRIP13 is related to radioresistance in LUAD and the specific mechanism, with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic.@*METHODS@#Three datasets, GSE18842, GSE19188 and GSE33532, were selected from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (|log FC|>1.5, P<0.05) in each of the three datasets using the R 4.1.3 software, and then Venn diagram was used to find out the differentially expressed genes common to the three datasets. The screened differential genes were then subjected to protein-protein interaction (PPI) analysis and module analysis with the help of STRING online tool and Cytoscape software, and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database, and the TRIP13 gene was identified as the main molecule for subsequent studies. Subsequently, the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line, H292DR. The radioresistance of H292DR cells was verified using cell counting kit-8 (CCK-8) assay and clone formation assay. The expression levels of TRIP13 in H292 and H292DR cells were measured by Western blot. Small interfering RNA (siRNA) was used to silence the expression of TRIP13 in H292DR cells and Western blot assay was performed. The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing, followed by the detection of changes in the expression levels of proteins closely related to homologous recombination, such as ataxia telangiectasia mutated (ATM) protein.@*RESULTS@#Screening of multiple GEO datasets, validation of external datasets and survival analysis revealed that TRIP13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy. And the results of gene set enrichment analysis (GSEA) of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy. Experimentally, TRIP13 expression was found to be upregulated in H292DR, and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation.@*CONCLUSIONS@#TRIP13 is associated with poor prognosis in LUAD patients treated with radiation, possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.

A Case of New Rapidly Progressing Ground-glass Nodule Lung Adenocarcinoma Near Primary Lesion after Stereotactic Body Radiation Therapy / 中国肺癌杂志

Ground-glass nodule (GGN) lung cancer often progresses slowly in clinical and there are few clinical studies on long-term follow-up of patients with operable GGN lung cancer treated with stereotactic body radiation therapy (SBRT). We present a successful case of GGN lung cancer treated with SBRT, but a new GGN was found in the lung adjacent to the SBRT target during follow-up. The nodule progressed rapidly and was confirmed as lung adenocarcinoma by surgical resection. No significant risk factors and related driving genes were found in molecular pathological findings and genetic tests. It deserves further study whether new GGN is related to the SBRT. This case suggests that the follow-up after SBRT should be vigilant against the occurrence of new rapidly progressive lung cancer in the target area and adjacent lung tissue.
.

Relationship between Bacteria in the Lower Respiratory Tract/Lung Cancer and the Development of Lung Cancer as well as Its Clinical Application / 中国肺癌杂志

Due to the advancement of 16S rRNA sequencing technology, the lower respiratory tract microbiota, which was considered non-existent, has been revealed. The correlation between these microorganisms and diseases such as tumor has been a hot topic in recent years. As the bacteria in the surrounding can infiltrate the tumors, researchers have also begun to pay attention to the biological behavior of tumor bacteria and their interaction with tumors. In this review, we present the characteristic of the lower respiratory tract bacteria and summarize recent research findings on the relationship between these microbiota and lung cancer. On top of that, we also summarize the basic feature of bacteria in tumors and focus on the characteristic of the bacteria in lung cancer. The relationship between bacteria in lung cancer and tumor development is also been discussed. Finally, we review the potential clinical applications of bacterial communities in the lower respiratory tract and lung cancer, and summarize key points of sample collection, sequencing, and contamination control, hoping to provide new ideas for the screening and treatment of tumors.
.

Hypothesis of Genetic Diversity Selection in the Occurrence and Development of Lung Cancer: Molecular Evolution and Clinical Significance / 中国肺癌杂志

So far, the monoclonal hypothesis of tumor occurrence and development cannot be justified. The genetic diversity selection hypothesis for the occurrence and development of lung cancer links Mendelian genetics with Darwin's theory of evolution, suggesting that the genetic diversity of tumor cell populations with polyclonal origins-monoclonal selection-subclonal expansion is the result of selection pressure. Normal cells acquire mutations in oncogenic driver genes and have a selective advantage over other cells, becoming tumor initiating cells; In the interaction with the tumor microenvironment (TME), the vast majority of initiating cells are recognized and killed by the human immune system. If immune escape occurs, the incidence of malignant tumors will greatly increase, and subclonal expansion, intratumour heterogeneity, etc. will occur. This article proposed the hypothesis of genetic diversity selection and analyzed its clinical significance.
.

Progress of Immunotherapy in EGFR-mutated Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently the first-line standard of care for patients with non-small cell lung cancer (NSCLC) that harbor EGFR mutations. Nevertheless, resistance to EGFR-TKIs is inevitable. In recent years, although immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm in advanced NSCLC without driver mutation, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Compared with wild-type tumors, tumors with EGFR mutations show more heterogeneity in the expression level of programmed cell death ligand 1 (PD-L1), tumor mutational burden (TMB), and other tumor microenvironment (TME) characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In this review, we summarized the clinical data with regard to the efficacy of ICIs in patients with EGFR-mutated NSCLC and deciphered the unique TME in EGFR-mutated NSCLC.
.

Study on the Role and Mechanism of METTL3 Mediating the Up-regulation of m6A Modified Long Non-coding RNA THAP7-AS1 in Promoting the Occurrence of Lung Cancer / 中国肺癌杂志

BACKGROUND@#Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment. Long non-coding RNA (lncRNA) THAP7-AS1 is known to be highly expressed in gastric cancer, but has been less studied in other cancers. The aim of the study is to explore the role and mechanism of methyltransferase-like 3 (METTL3) mediated up-regulation of N6-methyladenosine (m6A) modified lncRNA THAP7-AS1 expression in promoting the development of lung cancer.@*METHODS@#Samples of 120 lung cancer and corresponding paracancerous tissues were collected. LncRNA microarrays were used to analyze differentially expressed lncRNAs. THAP7-AS1 levels were detected in lung cancer, adjacent normal tissues and lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of THAP7-AS1 in lung cancer and the relationship between THAP7-AS1 expression and survival rate and clinicopathological parameters were analyzed. Bioinformatics analysis, methylated RNA immunoprecipitation (meRIP), RNA pull-down and RNA-immunoprecipitation (RIP) assay were used to investigate the molecular regulation mechanism of THAP7-AS1. Cell proliferation, migration, invasion and tumorigenesis of SPC-A-1 and NCI-H1299 cells were determined by MTS, colony-formation, scratch, Transwell and xenotransplantation in vivo, respectively. Expression levels of phosphoinositide 3-kinase/protein kenase B (PI3K/AKT) signal pathway related protein were detected by Western blot.@*RESULTS@#Expression levels of THAP7-AS1 were higher in lung cancer tissues and cell lines (P<0.05). THAP7-AS1 has certain diagnostic value in lung cancer [area under the curve (AUC)=0.737], and its expression associated with overall survival rate, tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). METTL3-mediated m6A modification enhanced THAP7-AS1 expression. The cell proliferation, migration, invasion and the volume and mass of transplanted tumor were all higher in the THAP7-AS1 group compared with the NC group and sh-NC group of SPC-A-1 and NCI-H1299 cells, while the cell proliferation, migration and invasion were lower in the sh-THAP7-AS1 group (P<0.05). THAP7-AS1 binds specifically to Cullin 4B (CUL4B). The cell proliferation, migration, invasion, and expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD), phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) were higher in the THAP7-AS1 group compared with the Vector group of SPC-A-1 and NCI-H1299 cells (P<0.05).@*CONCLUSIONS@#LncRNA THAP7-AS1 is stably expressed through m6A modification mediated by METTL3, and combines with CUL4B to activate PI3K/AKT signal pathway, which promotes the occurrence and development of lung cancer.

Cytology Smears of Rapid On-site Evaluation as Supplemental Material for Molecular Testing of Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#The thoracic small biopsy sampling procedure including transbronchial forceps lung biopsy (TBLB) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) can be accompanied by rapid on-site evaluation (ROSE) of sample material to provide immediate feedback for the proceduralist. The present study aims to investigate the supplemental effect of ROSE smear samples for lung cancer molecular test.@*METHODS@#In a retrospective study, 308 patients admitted to our hospital from August 2020 to December 2022 undergoing diagnostic TBLB and EBUS-TBNA with ROSE and subsequently diagnosed as non-small cell lung cancer (NSCLC) were analyzed. The matched formalin-fixed paraffin-embedding (FFPE) tissue section and ROSE smears for tumor cellularity were compared. DNA yields of smears were determined. Real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS) were performed on adequate smear samples.@*RESULTS@#ROSE smear samples were enriched in tumor cells. Among 308 biopsy samples, 78 cases (25.3%) exhibited inadequate FFPE tissue sections, whereas 44 cases (14.3%) yielded adequate smear samples. Somatic mutations detected in the FFPE tissue section samples were also detected in the matching adequate smear sample.@*CONCLUSIONS@#ROSE smear samples of the thoracic small biopsies are beneficial supplemental materials for ancillary testing of lung cancer. Combined use of cytology smear samples with traditional FFPE section samples can enhance the detection rate of informative mutations in patients with advanced NSCLC. We recommend that the laboratory could further evaluate the ROSE cell smears of the patient when FFPE tissue sections are inadequate, and that adequate cell smears can be used as a supplemental source for the molecular testing of NSCLC.