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.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Rapid On-site Evaluation ; Retrospective Studies ; Molecular Diagnostic Techniques ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods*

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.
Humans ; Lung Neoplasms/pathology* ; RNA, Long Noncoding/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Up-Regulation ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Methyltransferases/metabolism* ; Cullin Proteins/genetics*

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.
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Humans ; Lung Neoplasms/pathology* ; Radiosurgery ; Retrospective Studies ; Adenocarcinoma of Lung/surgery* ; Lung/pathology*

OBJECTIVE: To analyze the correlation between the mRNA levels of breast cancer resistance protein (BCRP) and lung-specific X protein (LUNX) genes with pathological types and stages of patients with non-small cell lung cancer (NSCLC) and their significance for prognosis. METHODS: Eighty nine patients with NSCLC admitted to Huaihe Hospital of Henan University between June 2015 and June 2018 were recruited, with 55 patients with benign lung lesions admitted during the same period of time selected as the control group. The mRNA levels of BCRP and LUNX genes were detected in the peripheral blood samples from the two groups, and their correlation with the clinicopathological characteristics and prognosis of the patients was analyzed. RESULTS: The expression rates of BCRP and LUNX mRNA in the NSCLC group were significantly higher compared with the control group (P < 0.05). The level of BCRP mRNA of the NSCLC patients has correlated with the degree of differentiation and TNM staging (P < 0.05), but not with gender, age, smoking, pathological types and lymph node metastasis (P > 0.05). The level of LUNX mRNA of them has correlated with the degree of differentiation, TNM staging and lymph node metastasis (P < 0.05), but not with gender, age, smoking, and pathological types (P > 0.05). Compared with those with no expression, the overall survival rate of patients with BCRP and LUNX expression was significantly lower (P < 0.05). The degree of differentiation, TNM staging, lymph node metastasis, and expression of the BCRP and LUNX mRNA may all affect the prognosis of the patients. CONCLUSION The levels of BCRP and LUNX mRNA in the peripheral blood of patients with NSCLC are significantly increased. The expression of BCRP mRNA is correlated with the degree of differentiation and TNM staging, whilst the expression of LUNX mRNA is correlated with the differentiation degree, TNM staging and lymph node metastasis. Both may be used as independent predictors for the prognosis of patients with NSCLC.
Humans ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Biomarkers, Tumor/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Glycoproteins/genetics* ; Lung Neoplasms/pathology* ; Lymphatic Metastasis ; Neoplasm Proteins/genetics* ; Phosphoproteins/genetics* ; Prognosis ; RNA, Messenger/genetics*

OBJECTIVE: To study the clinical, imaging, and pathological features of pulmonary lymphoma. METHODS: Patients with pulmonary lymphoma diagnosed by lung biopsy in Zhongda Hospital Affiliated to Southeast University from November 2013 to December 2020 were collected and divided into secondary pulmonary lymphoma (SPL) group and primary pulmonary lymphoma (PPL) group according to the primary site of lymphoma. The clinical characteristics, stages, imaging features, diagnostic methods and pathological types of the two groups were analyzed. RESULTS: A total of 22 patients were included, 10 cases were PPL and 12 cases were SPL. The main symptoms of the two groups were cough, dyspnea and chest pain. The proportion of stage III/IV patients and international prognostic index (IPI) in SPL group were significantly higher than those in PPL group (P<0.05). Chest high-resolution computed tomography (HRCT) mainly showed masses, nodules and consolidation in both groups. The proportions of single mass and air bronchial sign in PPL group were significantly higher than those in SPL group, while the proportions of multiple nodules, mediastinal/hilar lymphadenopathy and pleural effusion were significantly lower (P<0.05). The max standardized uptake value (SUV_max), peak standardized uptake value (SUV_peak), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in PPL group were lower than those in SPL group, but the differences were not statistically significant (P>0.05). In PPL group, 8 cases were diagnosed by transbronchial lung biopsy (TBLB) and 2 cases by percutaneous lung puncture. In SPL group, 4 cases were diagnosed by TBLB, 7 cases by percutaneous lung puncture, and 1 case by surgery. 95.5% patients were diagnosed by non-surgical methods. The main pathological type of PPL was mucosa-associated lymphoid tissue (MALT) lymphoma, while that of SPL was diffuse large B-cell lymphoma (P<0.05). CONCLUSION The clinical symptoms of pulmonary lymphoma are nonspecific, but the chest HRCT has characteristic manifestations, which can also help to distinguish between SPL and PPL. ¹⁸F-FDG PET/CT is also a potential method to distinguish between SPL and PPL. TBLB and percutaneous lung puncture biopsy are reliable methods for the diagnosis of lung lymphoma. The main pathological type of PPL is MALT lymphoma, while that of SPL is diffuse large B-cell lymphoma.
Humans ; Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Lung Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Lymphoma, B-Cell, Marginal Zone/diagnosis* ; Prognosis ; Retrospective Studies

BACKGROUND: There have been many significant advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC). However, the mechanism underlying the progression of NSCLC is still not clear. Plant homodomain finger-like domain-containing protein 5A (PHF5A) plays an important role in processes of chromatin remodeling, morphological development of tissues and organs and maintenance of stem cell pluripotency. This study aims to investigate the role of PHF5A in the proliferation and migration of NSCLC. METHODS: A549 and PC-9 PHF5A overexpression cell lines were constructed. PHF5A expression was decreased in H292 and H1299 cells by using siRNA. Flow cytometry was used to detect the cell cycle. MTT assay and clone formation assay were used to examine the proliferative ability of NSCLC, while migration assay and wound healing assay were performed to evaluate the ability of migration. Western blot analysis was used to measure the expressions of PI3K, p-AKT and the associated downstream factors. RESULTS: Up-regulation of PHF5A in A549 and PC-9 cells increased the proliferation rate, while down-regulation of PHF5A in H292 and H1299 cells inhibited the proliferation rate at 24 h, 48 h and 72 h (P<0.05). The metastatic ability was elevated in the PHF5A-overexpresion groups, while reduced in the PHF5A-down-regulation group (P<0.05). In addition, reduced expression of PHF5A induced cell cycle arrest at G1/S phase (P<0.05). Furthermore, decreased expression of PHF5A reduced the expression levels of PI3K, phosphorylation of AKT, c-Myc (P<0.05) and elevated the expression of p21 (P<0.05). CONCLUSIONS These results demonstrated that PHF5A may play an important role in progression of NSCLC by regulating the PI3K/AKT signaling pathway.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic ; Trans-Activators/genetics* ; RNA-Binding Proteins/metabolism*

BACKGROUND: With the extensive application of segmental lung resection in the treatment of early-stage lung cancer, how to complete segmentectomy more accurately and minimally invasively has become a research hotspot. The aim of this study is to explore the application of three-dimensional computed tomography bronchography and angiography (3D-CTBA) combined with perfusion area recognition technique in single-hole thoracoscopic complex segmentectomy. METHODS: From January 2021 to January 2022, the clinical data of 112 consecutive patients undergoing single-port thoracoscopic complex segmentectomy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The three-dimensional reconstruction combined with perfusion area identification technique was used to perform the operation and the clinical data were analyzed. RESULTS: The average operation time was (141.1±35.4) min; the initial time of intersegmental plane display was (12.5±1.7) s; the maintenance time of intersegmental plane was (114.3±10.9) s; the intersegmental plane was clearly displayed (100%); the amount of bleeding was [10 (10, 20)] mL; the total postoperative drainage volume was (380.5±139.7) mL; the postoperative extubation time was (3.9±1.2) d; and the postoperative hospitalization time was (5.2±1.6) d. Postoperative complications occurred in 8 cases. CONCLUSIONS The advantages of 3D-CTBA combined with perfusion area recognition technique are fast, accurate and safe in identifying intersegmental boundary in single-port thoracoscopic complex segmentectomy, which could provide guidances for accuratding resection of tumors, shortening operation time and reducing surgical complications.
Humans ; Lung Neoplasms/pathology* ; Bronchography ; Pneumonectomy/methods* ; Retrospective Studies ; Thoracic Surgery, Video-Assisted/methods* ; Tomography, X-Ray Computed ; Angiography/methods* ; Perfusion

Lung cancer is the leading cause of cancer death in the world today, and adenocarcinoma is the most common histopathological type of lung cancer. In May 2021, World Health Organization (WHO) released the 5th edition of the WHO classification of thoracic tumors, which classifies invasive non-mucinous adenocarcinoma (INMA) into lepidic adenocarcinoma, acinar adenocarcinoma, papillary adenocarcinoma, solid adenocarcinoma, and micropapillary adenocarcinoma based on its histological characteristics. These five pathological subtypes differ in clinical features, treatment and prognosis. A complete understanding of the characteristics of these subtypes is essential for the clinical diagnosis, treatment options, and prognosis predictions of patients with lung adenocarcinoma, including recurrence and progression. This article will review the grading system, morphology, imaging prediction, lymph node metastasis, surgery, chemotherapy, targeted therapy and immunotherapy of different pathological subtypes of INMA.
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Humans ; Lung Neoplasms/pathology* ; Adenocarcinoma of Lung/pathology* ; Adenocarcinoma/pathology* ; Prognosis ; Lymphatic Metastasis ; Neoplasm Staging ; Retrospective Studies

Non-small cell lung cancer (NSCLC) can be detected with enlarged lymph nodes on imaging, but their benignity and malignancy are difficult to determine directly, making it difficult to stage the tumor and design radiotherapy target volumes. The clinical diagnosis of malignant lymph nodes is often based on the short diameter of lymph nodes ≥1 cm or the maximum standard uptake value ≥2.5, but the sensitivity and specificity of these criteria are too low to meet the clinical needs. In recent years, many advances have been made in diagnosing benign and malignant lymph nodes using other imaging parameters, and with the development of radiomics, deep learning and other technologies, models of mining the image information of enlarged lymph node regions further improve the diagnostic accuracy. The purpose of this paper is to review recent advances in imaging-based diagnosis of benign and malignant enlarged lymph nodes in NSCLC for more accurate and noninvasive assessment of lymph node status in clinical practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Diagnostic Imaging ; Lung Neoplasms/pathology* ; Lymph Nodes/pathology* ; Sensitivity and Specificity

Chemokine-like factor-like MARVEL transmembrane domain containing member/chemokine-like factor superfamily member (CMTM/CKLFSF) including CKLF and CMTM1-CMTM8 are a new family of proteins linking chemokines and transmembrane superfamilies. CMTM not only have broad chemotactic activities, but also associate with hematopoietic system, immune system, and tumor development and metastasis closely. CMTM proteins are involved in key biological processes of cancer development, which include activation and recycling of growth factor receptors, cell proliferation and metastasis, and regulation of the tumor immune microenvironment. This is a new focus of research on the relationship between CMTM and tumors, because CMTM4/CMTM6 can be considered as a regulator for programmed cell death ligand 1 (PD-L1). This paper reviews the role of CMTM family members on cancer, especially in tumor growth, metastasis and immune escape, summarize the latest findings on the relationship between CMTM and non-small cell lung cancer, and explores the potential clinical value of CMTM as a novel drug target or biomarker.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms ; MARVEL Domain-Containing Proteins/metabolism* ; Cell Proliferation ; Chemokines/metabolism* ; Tumor Microenvironment