BACKGROUND:SMARCA4-deficient pulmonary neoplasms have emerged as a major focus of lung cancer research in recent years. This subtype is characterized by aggressive behavior and poor prognosis. However, radiotherapy-related studies in this population remain scarce, and evidence is lacking regarding the optimal selection of radiotherapy parameters and the sequencing of combination with immunotherapy. The present study aimed to evaluate the efficacy of radiotherapy in these tumors and to explore the prognostic value of radiotherapy parameters. METHODS:Clinical data of 88 patients with SMARCA4-deficient pulmonary neoplasms were retrospectively analyzed. Patients were divided into a radiotherapy group (n=20) and a non-radiotherapy group (n=68). Overall survival (OS) was compared between groups using the Kaplan-Meier method. Subgroup analyses were performed for radiotherapy site, biological equivalent dose (BED), fractionation mode, and the timing of radiotherapy combined with immunotherapy. RESULTS:The radiotherapy group had a lower proportion of patients aged ≥60 years (25.0% vs 66.2%, P<0.001) and a higher proportion receiving immunotherapy (65.0% vs 33.8%, P=0.013) compared with the non-radiotherapy group. The median OS was not reached in the radiotherapy group, which was significantly superior to that in the non-radiotherapy group (22.9 mon, P=0.048). Among patients receiving radiotherapy, those who also received immunotherapy had a significantly longer median OS than those receiving radiotherapy alone. No statistically significant differences in OS were observed among subgroups stratified by radiotherapy site, BED, fractionation schedule or timing. CONCLUSIONS:Radiotherapy effectively improves OS in SMARCA4-deficient lung tumors, with synergistic potential when combined with immunotherapy. The lack of prognostic impact of radiotherapy parameters supports regimen simplification, while the timing of combined therapy needs refinement. These exploratory results lay a critical foundation for future large‑sample confirmatory studies.
Backgroud and objective Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC). Due to the lack of obvious symptoms and signs in the early stages, most patients are already in the middle or late stages at diagnosis. This makes treatment difficult and prognosis poor. Therefore, the identification of effective and specific biomarkers for lung cancer remains a focal area of research. So this study aimed to investigate the expression and clinical significance of S100 calcium-binding protein P (S100P) in LUAD. Methods Tissue samples of LUAD (n=50), adjacent normal lung tissue (n=50), and benign inflammatory lesions (n=50) were collected from The Affiliated Cancer Hospital, Guangzhou Medical University, used as the LUAD group, normal group and benign group. Immunohistochemistry (SP method) was employed to detect the expression of S100P, C-C chemokine ligand 4 (CCL4), and cluster of differentiation 8 (CD8) proteins. Correlation analyses were carried out. Results Database analysis (UALCAN, GEPIA2) identified S100P as an mRNA with high expression in LUAD. Immunohistochemistry demonstrated that the protein levels of S100P and CCL4 were significantly higher in lung tissues of the LUAD group compared to those in the normal group and benign group (all P<0.05). The area under the curve (AUC) of S100P for differentiating LUAD was 0.943. The expression of S100P showed no significant correlation with age, sex, tumor size, or degree of differentiation (all P>0.05). Correlation analysis revealed that S100P expression was moderately positively correlated with CCL4 (r=0.611, P<0.001), and positively correlated with CD8+ lymphocyte infiltration (r=0.461, P<0.001). CCL4 expression was also positively correlated with CD8+ infiltration (r=0.400, P<0.001). Conclusion Database analysis indicates that S100P is highly expressed in LUAD and associated with a poor prognosis, making it a potential biomarker for the prognosis of LUAD. Clinical tissue analysis further shows that S100P expression is correlated with CD8+ lymphocyte infiltration in LUAD, suggesting that S100P can serve as a biomarker of lymphocyte infiltration and a potential predictor of the response to immune checkpoint inhibitors.
Background and objective C-ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) gene fusion-positive non-small cell lung cancer (NSCLC) is a high-risk subtype of lung cancer, and the accurate identification of this specific subtype is critically important. This study systematically analyzes the concordance between the results of next-generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) to validate the clinical value of IHC as an initial screening tool for ROS1 fusions. Methods Patients with NSCLC diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences between November 1, 2020 and November 30, 2022 were enrolled. All cases were tested for ROS1 gene fusion via NGS, re-examined with hematoxylin-eosin (HE) staining, and ROS1 protein expression and gene breakage were detected using IHC and FISH. The results of the three detection methods and their correlation with clinicopathological characteristics were compared. Results 22 were detected as ROS1 fusion-positive among 770 NSCLC cases. Histologically, all were lung adenocarcinoma, predominantly poorly differentiated. The main growth patterns included solid, acinar, and papillary types. IHC detection showed positive expression of ROS1 protein in all 22 cases, including 14 cases (63.6%) with strong diffuse positivity, resulting in a positive concordance rate of 100.0%. FISH detection revealed a typical isolated signal pattern in 16 cases, with a positive concordance rate of 72.7%. The overall concordance rate among NGS, IHC, and FISH was 72.7%. Conclusion ROS1 fusion-positive NSCLC exhibits characteristic clinicopathological features. In ROS1 fusion-positive cases confirmed by NGS, IHC serves as a highly sensitive tool with 100.0% sensitivity, suggesting its potential as an initial screening method, but its specificity still needs further verification. NGS testing is recommended as a priority in cases with strong ROS1 IHC positivity. When strong IHC positivity is observed alongside atypical FISH signals, NGS becomes a key technique for confirmation and precise identification of fusion partners and breakpoints. An integrated diagnostic strategy combining histomorphological evaluation, IHC preliminary screening, and NGS validation facilitates accurate diagnosis of ROS1-positive lung cancer, thereby guiding clinical targeted therapy implementation.
Interstitial lung disease (ILD) is characterized by varying degrees of inflammation and fibrosis of the pulmonary interstitium, posing a significant threat to human health. Patients with ILD have a significantly higher risk of developing lung cancer compared to the general population, which has led to growing clinical attention to the condition of ILD combined with lung cancer (ILD-LC). Nowadays, surgical intervention remains the primary treatment option for patients with ILD-LC. However, how to formulate individualized surgical strategies for this patient population represents a critical challenge in clinical practice. Additionally, patients with ILD-LC are prone to postoperative acute exacerbation of ILD (AE-ILD), which is often challenging to detect at an early stage and severely compromises prognosis. Against this background, this article systematically reviews key aspects of ILD-LC, including differential diagnosis, surgical strategies, and perioperative management, with particular emphasis on the recognition and management of postoperative AE-ILD. It aims to provide a reference for the surgical treatment of ILD-LC and to outline directions for future research.
The mesenchymal-epithelial transition factor (MET) gene, located on human chromosome 7, exerts critical regulatory roles in cellular processes including proliferation, migration, invasion, and angiogenesis. As a key driver gene in non-small cell lung cancer (NSCLC), MET abnormalities encompass MET exon 14 (METex14) skipping mutations, gene amplification, protein overexpression, gene fusions, and activating mutations. This consensus, developed by the Lung Cancer Specialty Committee of the Chinese Elderly Health Care Association, updates the 2025 version with several key modifications: elevating the recommendation level for MET amplification and protein overexpression testing, advocating routine testing for all newly diagnosed NSCLC patients and those with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs); standardizing targeted therapy approaches for MET amplification in driver gene-negative settings and following EGFR-TKIs resistance; and subdividing MET protein overexpression-related management into post-EGFR-TKIs resistance and driver gene-negative categories with corresponding treatment protocols, thereby offering more actionable guidance for precise clinical decision-making.
Well-differentiated papillary mesothelial tumor (WDPMT) is a rare neoplasm characterized by a distinct papillary architecture, bland cytological features, and a propensity for superficial spread without stromal invasion. We herein report the diagnosis and management of a patient with pleural WDPMT presenting predominantly with recurrent spontaneous pneumothorax and pleural effusion, along with a review of the current literature on this entity. The patient was a 58-year-old female who presented with a two-week history of chest tightness and dyspnea on a background of recurrent spontaneous pneumothorax and pleural effusion over the preceding seven years. She had experienced four episodes of recurrence during that period and denied any history of asbestos exposure. Thoracoscopic exploration revealed pulmonary bullae, pleural effusion and pneumothorax, pleural thickening, and scattered grayish-white nodules on both the visceral and parietal pleura. Histopathological examination of the pleural nodule biopsy confirmed the diagnosis of WDPMT. Based on the features of this case and a review of the literature, clinicians should be aware that WDPMT may present with the atypical manifestation of recurrent spontaneous pneumothorax accompanied by pleural effusion.
Lung cancer ranks among malignant neoplasms with the highest incidence and mortality, and its diagnosis and treatment are complicated, requiring multidisciplinary participation. Multidisciplinary team (MDT) consultation is the core model for modern lung cancer management. By pooling the expertise of specialists from diverse disciplines, MDT develops optimal individualized treatment regimens for patients and markedly improves diagnostic and therapeutic quality as well as patient prognosis. This article systematically summarizes the organizational framework, standardized procedures and clinical value of lung cancer MDT, alongside key problems in its popularization including obstacles in data integration, inconsistent decision-making efficiency and imbalanced resource allocation. It elaborates on the innovative effect of new technologies represented by artificial intelligence large language models on conventional MDT modes, and analyzes their application value in high-efficiency integration of multimodal medical data, real-time evidence-based decision-making support, optimization of consultation procedures and resources, as well as precise individualized treatment, so as to furnish theoretical basis and development ideas for establishing a new-generation intelligent, efficient and precise lung cancer MDT platform.
With the wide application of low-dose spiral computed tomography and the advancement of imaging technology, the detection rate of pulmonary nodules has significantly increased. However, the traditional "one-size-fits-all" management strategy has been unable to meet the needs of precise diagnosis and treatment. This expert consensus was initiated by Professor Chunxia SU’s team and Professor Chang CHEN’s team from Shanghai Pulmonary Hospital and jointly formulated by experts from multiple disciplines including oncology, respiratory medicine, thoracic surgery, interventional medicine, radiology, and pathology. The aim is to provide scientific and practical decision-making references for clinical controversies that are less addressed or have differences in existing guidelines. The consensus uses the GRADE method for evidence assessment and forms 18 recommendations through two rounds of Delphi questionnaire surveys, focusing on differentiated screening for special populations, artificial intelligence assisted diagnosis, robot-assisted puncture, application of molecular markers, active monitoring of low-risk nodules, timing of invasive intervention, termination conditions of follow-up, management strategies for multiple nodules, and selection of individualized lymph node dissection range and surgical methods for early-stage lung cancer. This consensus would provides supplementary guidance for the entire process of precise management of pulmonary nodules from screening to treatment, with expectation of improving the long-term survival rate of lung cancer patients while minimizing unnecessary medical interventions and enhancing the quality of life of patients.
Lung adenocarcinoma (LUAD) is the most common and highly aggressive subtype of non-small cell lung cancer, characterized by metabolic reprogramming with enhanced glycolysis. Upregulation of key glycolytic enzymes [hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA)] and lactate accumulation not only support tumor energy production and biosynthesis but also promote tumor progression and immune evasion through lactate-mediated immunosuppression and epigenetic regulation such as histone lactylation. Oncogenic signaling pathways, including phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), hypoxia-inducible factor-1α (HIF-1α), and MYC proto-oncogene (c-Myc), synergistically drive glycolytic activation, thereby reshaping the tumor immune microenvironment and influencing therapeutic responses. In recent years, glycolysis-related metabolic enzymes and imaging parameters have shown promising potential in the early diagnosis, prognostic evaluation, and treatment monitoring of LUAD, with multi-omics integration further facilitating their clinical translation. Collectively, glycolytic reprogramming is not only a hallmark metabolic feature of LUAD but also a critical nexus linking immunosuppression, therapeutic resistance, and precision medicine. This review summarizes the molecular mechanisms, associated biomarkers, and targeted strategies of glycolytic reprogramming, aiming to provide insights for early screening, risk stratification, and metabolism-targeted therapies in LUAD.
Epidermal growth factor receptor (EGFR) gene mutations are the most common driver mutations in non-small cell lung cancer (NSCLC). This article reports a case of a patient with EGFR-sensitive mutant lung adenocarcinoma who developed secondary transformation to small cell lung cancer (SCLC) and anaplastic lymphoma kinase (ALK) gene fusion following first-line Osimertinib therapy. This paper reported a case of concurrent SCLC transformation and ALK fusion occurring after Osimertinib treatment, suggesting that the two can coexist as dual drug resistance mechanisms. Re-biopsy combined with genetic testing is essential for identifying drug resistance mechanisms and guiding individualized therapy.
Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide. The current treatment methods have limited efficacy, and the prognosis of patients is poor. There is an urgent need to explore new therapeutic targets and strategies. Epigenetic modification disorders are closely related to the occurrence and development of tumors. Among them, histone deacetylase 1 (HDAC1), as a key epigenetic regulatory molecule, participates in the regulation of biological processes such as cell proliferation, differentiation, and apoptosis. HDAC1 is highly expressed in lung cancer, and its expression level is closely related to the malignancy degree, clinical stage, and poor prognosis of lung cancer. Abnormal activation of HDAC1 is also one of the core factors for the resistance of lung cancer to chemotherapy, targeted therapy, and immunotherapy. The development of HDAC1 inhibitors provides a new direction for the treatment of lung cancer, and the combination with chemotherapy, targeted therapy, and immunotherapy can significantly enhance the synergistic anti-tumor effect. This article systematically reviews the structural characteristics and physiological functions of HDAC1, deeply explores its regulatory mechanism in lung cancer, elaborates on its association with lung cancer resistance, and summarizes the research and development progress, clinical trial status, and challenges of HDAC1 inhibitors, with the aim of providing new ideas for the precise treatment of lung cancer.
Small cell lung cancer (SCLC), characterized by high aggressiveness, early metastasis, and poor prognosis, has long been a major challenge in lung cancer treatment. In recent years, the advent of immune checkpoint inhibitors (ICIs) has significantly improved overall survival in patients with SCLC and has become a new standard of care; however, substantial room for further improvement in clinical outcomes remains. As an emerging T cell-targeted immunotherapy, delta-like ligand 3-T cell engager (DLL3-TCE) precisely directs T cells to attack tumor cells and have demonstrated breakthrough potential in the treatment of SCLC. Tarlatamab, a representative agent in this class, has been approved for clinical use, and multiple TCE agents are currently under clinical development. Although DLL3-TCE shows promising prospects in the clinical management of SCLC, as a novel therapeutic modality, many clinicians still lack an in-depth understanding of their mechanisms of action, appropriate patient populations, and clinical management. To standardize the clinical application of DLL3-TCE in China, the Small Cell Lung Cancer Expert Committee of the Chinese Society of Clinical Oncology convened a consensus panel to develop the Chinese Expert Consensus on Delta-like Ligand 3-T Cell Engager Therapy for SCLC based on evidence-based medicine and expert practical experience, with the aim of providing standardized guidance for the clinical use of DLL3-TCE agents.
Background and objective The incidence and mortality rates of non-small cell lung cancer (NSCLC) are generally on the rise, and the overall prognosis of patients remains poor. Current clinical treatment strategies have significant limitations. Notably, the bioactive components of traditional Chinese medicine possess unique advantages, including diverse targets of action and low toxicity. Ziyuglycoside II (ZGS II), a major active component of Sanguisorba officinalis L, has been shown to inhibit cancer cell proliferation, migration, and invasion. This property confers potential application value and developmental prospects for its use in cancer therapy. Nevertheless, the effects of ZGS II on NSCLC and the underlying mechanisms remain unclear. This study aimed to investigate the anti-tumor molecular mechanism of ZGS II in NSCLC and to explore the potential of being a novel therapeutic strategy for improving the prognosis of NSCLC patients. Methods First, the cell counting kit-8 (CCK-8) and the colony formation assay were used to detect the changes in the viability and proliferation ability of NSCLC cells after treatment with ZGS II. Wound-healing and Transwell assays were used to evaluate the effects of ZGS II on migration and invasion abilities. Western blot, Lentiviral transfection, wound healing assay, and Transwell assay were used to study the effects of ZGS II on the integrin β4/focal adhesion kinase (ITGB4/FAK) signaling pathway. A rescue experiment was then performed using the FAK agonist ZINC40099027. A nude mouse xenograft model was used to evaluate the inhibitory effect of ZGS II on NSCLC metastasis in vivo. Results ZGS II inhibited proliferation, migration, and invasion of NSCLC cells and suppressed the protein expression of ITGB4. This inhibitory effect was significantly enhanced upon ITGB4 knockdown. Meanwhile, total FAK expression remained nearly unchanged, but the protein expression level of phosphorylated focal adhesion kinase (p-FAK) was suppressed. Following the addition of an FAK activator, cell migration rate and the number of cells crossing the Transwell membrane increased, reversing the inhibitory effects of ZGS II on cell migration and invasion. Therefore, the anti-tumor effect of ZGS II depends on the reduced activation of the ITGB4/FAK signaling pathway. The nude mouse xenograft experiment results showed that ZGS II effectively inhibited tumor growth in nude mice. Conclusion ZGS II inhibits proliferation, metastasis, and tumor growth in NSCLC by suppressing the ITGB4/FAK pathway. These findings highlight the potential of ZGS II as a promising drug for treating metastatic NSCLC and lay the foundation for its clinical research.
BACKGROUND:Non-small cell lung cancer (NSCLC) is one of the causes of cancer-related deaths worldwide. Although platinum-based chemotherapy is the main treatment method for advanced patients, acquired resistance often leads to treatment failure. Long non-coding RNAs (lncRNAs) play an important role in tumor occurrence and development, but the specific mechanism of their involvement in chemotherapy resistance in NSCLC is not yet fully understood. This study aims to explore the effect of LINC00641 on the microRNA-1306-5p (miR-1306-5p)/fibroblast growth factor receptor 3 (FGFR3) axis on the malignant progression and chemotherapy resistance of NSCLC cell line H1299. METHODS:The mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR); and the interaction was verified by the dual-luciferase reporter gene assay. H1299 cells were randomly divided into the following groups: CG group (normal culture), sh-NC group (transfected with sh-NC), sh-LINC00641 group (transfected with sh-LINC00641), sh-LINC00641+anti-NC group (transfected with sh-LINC00641 and anti-NC), sh-LINC00641+anti-miR-1306-5p group (transfected with sh-LINC00641 and anti-miR-1306-5p), mimic-NC group (transfected with mimic-NC), miR-1306-5p-mimics group (transfected with miR-1306-5p-mimics), miR-1306-5p-mimics+OE-NC group (transfected with miR-1306-5p-mimics and OE-NC), and miR-1306-5p-mimics+OE-FGFR3 group (transfected with miR-1306-5p-mimics and OE-FGFR3). Then cell proliferation, migration, and invasion were measured by plate colony formation assay, scratch assay, and Transwell assay, respectively. In addition, H1299/DDP cells were grouped as mentioned above. After that, the chemotherapy resistance of H1299/DDP cells was detected by the MTT method. And Western blot was implemented to detect the protein expressions of FGFR3, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 13 (MMP-13), integrin β1 in H1299 cells, and the P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) in H1299/DDP cells. RESULTS:In NSCLC tissues or cells (H1299, H1299/DDP), LINC00641 and FGFR3 were highly expressed, while miR‑1306‑5p was lowly expressed, and the expression trends of these three factors changed more significantly in the drug‑resistant cell line H1299/DDP (P<0.05). LINC00641 could negatively regulate miR‑1306‑5p in a targeted manner; and miR‑1306‑5p could negatively regulate FGFR3 in a targeted manner. Knockdown of LINC00641 (sh‑LINC00641) or overexpression of miR‑1306‑5p reduced the clone number, scratch healing rate, migration number, invasion number, and the expression of PCNA, MMP‑13, and integrin β1 proteins in H1299 cells (P<0.05), and also suppressed the optical density (OD)540 value and the expression of P‑gp and MRP1 proteins in H1299/DDP cells (P<0.05). In addition, inhibition of miR‑1306‑5p or overexpression of FGFR3 could reverse the inhibitory effects of LINC00641 knockdown or miR‑1306‑5p overexpression on the proliferation, migration, invasion, and chemoresistance of H1299 cells (P<0.05). CONCLUSIONS:Knockdown of LINC00641 can regulate the miR-1306-5p/FGFR3 axis, inhibit the malignant progression and chemotherapy resistance of NSCLC cells, and provide a new candidate target for molecular intervention of chemotherapy resistance in NSCLC.
Lung cancer is one of the most prevalent and lethal malignant tumors worldwide. In recent years, immune checkpoint inhibitors have significantly improved the survival outcomes of some patients with advanced non-small cell lung cancer; however, primary and acquired resistance remain important barriers limiting their clinical efficacy. Research has revealed that structural remodeling of the tumor microenvironment (TME) is one of the key factors involved in immunotherapy resistance. Efferocytosis is an important process by which tumor-associated macrophages clear apoptotic cells. In the lung cancer TME, the high apoptotic cell burden can lead to persistent activation of efferocytosis. Studies have shown that sustained efferocytosis is not merely a process of cellular debris clearance, but can also induce metabolic reprogramming in macrophages, including dysregulated lipid metabolism and enhanced glycolysis, and promote the secretion of immunosuppressive and tissue-repair-related factors. These changes further promote pathological angiogenesis, activation of cancer-associated fibroblasts, and excessive extracellular matrix deposition, thereby driving structural remodeling of the TME and forming an immune-excluded microenvironment characterized by vascular abnormalities and stromal fibrosis. This process restricts effector T-cell infiltration and impairs the efficacy of immune checkpoint inhibitors. This review describes the molecular mechanisms of macrophage efferocytosis in the lung cancer TME, focusing on its regulatory roles in metabolic reprogramming, pathological angiogenesis, and stromal fibrosis, and discusses potential therapeutic strategies targeting efferocytosis-related signaling pathways and TME structural remodeling, aiming to provide new insights into overcoming immunotherapy resistance in lung cancer.
Non-small cell lung cancer (NSCLC) remains at risk of recurrence after local treatment, and early identification of molecular residual disease before radiological progression is an important issue in risk stratification. Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) monitoring provides a promising molecular tool for recurrence risk assessment, response evaluation, and subsequent treatment stratification. However, surgery, thermal ablation, definitive chemoradiotherapy, and stereotactic body radiotherapy differ in tumor burden changes, tissue injury, and DNA release and clearance, leading to uncertainty regarding sampling time points, result interpretation, and clinical utility. This review summarizes recent advances in ctDNA-MRD monitoring after local treatment for NSCLC, focusing on ctDNA kinetics, candidate assessment windows, assay platform differences, prognostic value, and translational limitations in perioperative, thermal ablation, and radiotherapy settings. Current evidence suggests that perioperative ctDNA-MRD status is associated with pathological response, recurrence risk, and survival outcomes. In contrast, direct evidence after thermal ablation and stereotactic body radiotherapy remains limited, and proposed sampling time points should be regarded as candidate assessment windows rather than standardized recommendations. Further studies with standardized sampling, assay validation, and prospective interventional designs are needed to clarify the clinical value of ctDNA-MRD in adjuvant treatment selection, intensified surveillance, and individualized management.
Background and objective Non-small cell lung cancer (NSCLC) is associated with a high rate of postoperative recurrence, and conventional tumor-node-metastasis (TNM) staging does not fully reflect its biological heterogeneity. Hypoxia-inducible factor-1alpha (HIF-1α) plays a critical role in tumor progression and remodeling of the tumor immune microenvironment. However, the spatial distribution of HIF-1α and its prognostic significance in the context of different lymph node metastatic states remain unclear. This study aimed to investigate the densities of HIF-1α-expressing tumor cells, CD4+ T cells, and CD8+ T cells in the primary tumors of NSCLC patients, and to assess their associations with lymph node metastasis and postoperative recurrence. Methods 256 formalin-fixed paraffin-embedded primary tumor specimens from NSCLC patients who underwent radical resection at Shandong First Medical University Affiliated Cancer Hospital between January 1, 2014 and December 31, 2018 were retrospectively collected. Tissue microarrays containing both tumor center (TC) and invasive margin (IM) regions were constructed and multiplex immunofluorescence staining [HIF-1α/CD4/CD8/cytokeratin (CK)/4',6-diamidino-2-phenylindole (DAPI)] were performed to quantitatively analyze the densities of HIF-1α-expressing tumor cells (HIF-1α+CK+), HIF-1α+CD4+ T cells and HIF-1α+CD8+ T cells. Mann-Whitney U tests were used to compare cellular density differences between N0 versus N1-2 groups and N1 versus N2 subgroups, while Cox proportional hazards regression models were employed to identify critical recurrence-associated factors. Results The study ultimately included 256 patients with stage IA-IIIB NSCLC, with a median follow-up duration of 37.05 months, during which 87 cases (34.0%) experienced recurrence. Comparative analysis revealed that in both TC and IM regions, the N1-2 group exhibited significantly higher densities of HIF-1α+CK+ cells (P values: 0.039 and <0.001, respectively) and lower densities of HIF-1α+CD8+ cells (both P values: <0.001) compared to the N0 group, while no statistically significant differences were observed in the densities of HIF-1α+CK+ cells, HIF-1α+CD4+ cells, or HIF-1α+CD8+ cells between N1 and N2 subgroups within either TC or IM regions (all P>0.05). Multivariate Cox regression analysis showed that, among N0 patients, a low density of HIF-1α+CD8+ cells in the TC was an independent risk factor for recurrence in NSCLC patients [hazard ratio (HR)=1.998, 95%CI: 1.077-3.705, P=0.028]. In contrast, among N1 and N2 patients, the densities of HIF-1α+CK+ cells, HIF-1α+CD4+ T cells, and HIF-1α+CD8+ cells in both the TC and IM regions were not significantly associated with NSCLC recurrence. Conclusion In patients with NSCLC, lymph node metastasis is closely associated with alterations in the densities of HIF-1α-related cellular subpopulations in the primary tumor. A reduced density of HIF-1α+CD8+ cells in the TC of the primary lesion is significantly associated with postoperative recurrence in N0-stage NSCLC patients and may serve as a potential immunological marker for postoperative risk stratification.
With the popularization of low-dose computed tomography (LDCT) screening, the detection rate of ground-glass opacity (GGO) has been continuously increasing. Ground-glass opacity-featured lung adenocarcinoma is mostly characterized by indolent biological behavior and favorable prognosis. However, its progression is uncertain and recommendations vary among guidelines. This places clinicians in a dilemma between timely intervention and avoiding overdiagnosis and overtreatment, while patients often suffer from follow-up anxiety and decision-making confusion. To standardize the whole-process management on an evidence-based basis and fully incorporate patient values, this expert consensus systematically reviews the entire procedure of GGO diagnosis and treatment, establishes shared decision-making between doctors and patients as the core principle, and emphasizes formulating management strategies by integrating patient values, life goals and risk preferences. The consensus covers key components including the starting and ending ages for screening, limitations of imaging diagnosis and indications for invasive diagnosis, indications and timing of surgery, strategies for sublobar resection and lymph node management, management of multiple GGOs, non-surgical alternative therapies, reliability of intraoperative frozen-section pathology, postoperative enhanced recovery and pain management, eligible populations for adjuvant therapy, and follow-up strategies. By promoting multidisciplinary collaboration and structured communication, this consensus aims to facilitate the transformation of the diagnosis and treatment model from disease-centered to patient value-centered, improve medical quality and patient satisfaction, reduce overtreatment, and promote doctor-patient harmony.
Background and objective With the wide application of uniportal video-assisted thoracoscopy in the diagnosis and treatment of small pulmonary nodules, the optimization of postoperative chest tube management has become a focus of enhanced recovery after thoracic surgery. This study aimed to investigate the safety and non-inferiority of a no-drain strategy following uniportal video-assisted thoracoscopic wedge resection. Methods A total of 203 eligible patients who underwent surgery between January 2023 and May 2025 were enrolled and allocated to the no-drain group (n=53) and the drain group (n=150). After propensity score matching (PSM), 41 well-balanced pairs were generated. Non-inferiority testing combined with Bayesian analysis was performed to assess postoperative outcomes. Results After PSM, the no-drain group met the predefined non-inferiority criteria for the incidence of postoperative fever (19.51% vs 26.83%), pleural effusion (24.39% vs 21.95%), and the proportion of patients requiring additional analgesics (12.20% vs 9.76%), with the upper bound of the 95%CI for between-group differences not exceeding the 10% non-inferiority margin. The no-drain group demonstrated a significantly shorter median postoperative length of stay (2.00 vs 3.00 d, P<0.001) and lower visual analogue scale (VAS) scores on postoperative day 1 (P=0.0495), with non-inferiority confirmed. However, non-inferiority was not established for secondary intervention rates (primarily chest tube reinsertion, 4.88% vs 0.00%) or radiologic complications (73.17% vs 65.85%), as the upper limit of the 95%CI for the between-group differences exceeded the 10% margin. Bayesian analysis showed that the probability that the positive rate of imaging-related complications in the no-drain group was higher than that in the drain group was 77.18%, and the probability that the absolute value of the difference in positive rates between the two groups greater than 10.0% was 44.45%. Conclusion In carefully selected low-risk patients, a no-drain strategy following uniportal thoracoscopic wedge resection may reduce postoperative pain and shorten hospital stay, while meeting non-inferiority criteria for key safety outcomes. However, non-inferiority was not demonstrated for secondary chest tube insertion or radiologic complications. Enhanced postoperative monitoring is therefore essential to ensure clinical safety.
Non-small cell lung cancer (NSCLC) is characterized by high incidence and mortality, with a low five-year survival rate. Lactate metabolism plays a central role in the metabolic reprogramming of NSCLC. Beyond serving as the end-product of glycolysis, lactate accumulates in the tumor microenvironment (TME), contributing to acidification, and can also enter the tricarboxylic acid cycle to participate in energy metabolism. Moreover, the G protein-coupled receptor 81 (GPR81)/phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling axis induces the expression of immune checkpoint molecules, such as programmed death-ligand 1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), thereby suppressing the functions of T lymphocytes and natural killer cells and establishing an immunosuppressive microenvironment. Lactate further promotes epithelial-mesenchymal transition and tumor metastasis, and drives NSCLC chemoresistance and relapse via histone lactylation. Clinical studies indicate that enhanced lactate metabolism is associated with NSCLC progression and chemotherapy resistance, while targeting lactate metabolism in combination with immunotherapy exerts synergistic antitumor effects. Therefore, comprehensive inhibition of lactate metabolism together with enhancement of antitumor immunity may improve the efficacy of precision therapy in NSCLC.
