BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Programmed cell death 1 (PD-1) inhibitor therapy for lung adenocarcinoma may induce rare but severe hematologic adverse events, including severe anemia. Although glucocorticoids are recommended for managing immune-related adverse events, therapeutic experience with PD-1 inhibitor-induced severe anemia remains limited, and its efficacy and safety have not been fully validated. This article reports a case of advanced lung adenocarcinoma in which severe anemia developed following combination therapy with chemotherapy and PD-1 inhibitor. After comprehensive evaluation, the patient was diagnosed with anemia of inflammation (AI) and achieved significant hemoglobin recovery following high-dose glucocorticoid treatment. These findings may provide new insights into the recognition and management of this rare hematologic toxicity in clinical practice.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Anemia/etiology* ; Immunotherapy/adverse effects* ; Lung Neoplasms/immunology* ; Male ; Antibodies, Monoclonal/therapeutic use* ; Middle Aged

Epidermal growth factor receptor (EGFR) exon 20 mutations represent a rare subset of genetic alterations in non-small cell lung cancer (NSCLC). Among them, the complex mutation H773_V774delinsLM is exceedingly uncommon, accounting for only 0.2%-1% of all EGFR mutations. It is currently believed that rare EGFR mutations are generally resistant to the first- and second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although the third-generation EGFR-TKIs have shown some efficacy in certain rare mutations, clinical evidence regarding their use in NSCLC patients with the H773_V774delinsLM mutation remains sparse, and their efficacy and safety are yet to be clarified. Here, we present the first documented case of a patient with EGFR H773_V774delinsLM-mutant lung adenocarcinoma who experienced remarkable tumor regression following treatment with furmonertinib. This case highlights the potential utility of furmonertinib in treating patients with this rare EGFR mutation and may provide valuable insight into emerging treatment strategies for similarly affected patients.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Exons/genetics* ; Lung Neoplasms/enzymology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*

BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.
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Humans ; Female ; ErbB Receptors/metabolism* ; Endometrial Neoplasms/genetics* ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Adenocarcinoma of Lung/drug therapy* ; Treatment Failure ; Middle Aged ; Adenocarcinoma/genetics*

BACKGROUND: Lung adenocarcinoma is an important pathohistologic subtype of non-small cell lung cancer (NSCLC). Invasive non-mucinous pulmonary adenocarcinomas (INMA) tend to have a poor prognosis due to their significant heterogeneity and diverse histologic components. Establishing a histologic grading system for INMA is crucial for evaluating its malignancy. In 2021, the International Association for the Study of Lung Cancer (IASLC) proposed that a new histological grading system could better stratify the prognosis of INMA patients. The aim of this study was to establish a visualized nomogram model to predict INMA IASLC grading preoperatively by means of dual-energy computed tomography (DECT), fractal dimension (FD), clinical features and conventional CT parameters. METHODS: A total of 112 patients with INMA who underwent preoperative DECT were retrospectively enrolled from March 2021 to January 2025. Patients were categorized into low-intermediate grade and high grade groups based on IASLC grading. The clinical characteristics and conventional CT parameters, including baseline features, biochemical markers, and serum tumor markers, were collected. DECT-derived parameters, including iodine concentration (IC), effective atomic number (eff-Z), and normalized IC (NIC), were collected and determined as NIC ratio (NICr) and fractal dimension (FD). Univariate analysis was employed to compare differences in conventional characteristics and DECT parameters between the two groups. Variables demonstrating statistical significance were subsequently incorporated into a multivariate Logistic regression analysis. A nomogram model integrating clinical data, conventional CT parameters, and DECT parameters was developed to identify independent predictors for IASLC grading of INMA. The discriminatory performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariate analysis identified smoking history [odds ratio (OR)=2.848, P=0.041], lobulation sign (OR=2.163, P=0.004), air bronchogram (OR=7.833, P=0.005), eff-Z in arterial phase (OR=4.266, P<0.001), and IC in arterial phase (OR=1.290, P=0.012) as independent and significant predictors for IASLC grading of INMA. The nomogram model constructed based on these indicators demonstrated optimal predictive performance, achieving an area under the curve (AUC) of 0.804 (95%CI: 0.725-0.883), with specificity and sensitivity of 85.3% and 65.7%, respectively. CONCLUSIONS The nomogram model based on clinical features, imaging features and spectral CT parameters have a large potential for application in the preoperative noninvasive assessment of INMA IASLC grading.
Humans ; Nomograms ; Female ; Male ; Middle Aged ; Tomography, X-Ray Computed/methods* ; Lung Neoplasms/pathology* ; Aged ; Retrospective Studies ; Adenocarcinoma of Lung/pathology* ; Neoplasm Grading ; Adult

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a variety of solid tumors and hematological malignancies. Adverse reactions caused by ICIs have been gradually focused on. Cytomegalovirus (CMV) gastritis after ICIs treatment is relatively rare. Here we reported a case of advanced lung adenocarcinoma who experienced recurrent upper abdominal pain and vomiting after Pembrolizumab treatment. CMV gastritis was diagnosed through gastroscopy. The patient's symptoms improved after antiviral treatment. During the treatment of ICIs, attention should be paid to the differential diagnosis of upper abdominal pain symptoms, and vigilance should be maintained against CMV gastritis. It is difficult to differentiate CMV gastritis and immune-related gastritis judging from symptoms, and gastroscopy is important for differential diagnosis.
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Humans ; Adenocarcinoma of Lung/drug therapy* ; Cytomegalovirus/physiology* ; Cytomegalovirus Infections ; Gastritis/diagnosis* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/drug therapy*

BACKGROUND: Lung cancer currently ranks first globally in both incidence and mortality. Pemetrexed (PMX) serves as a first-line treatment for lung adenocarcinoma (LUAD), but the patients often develop drug resistance during therapy. Milk exosome (mEXO) have the advantages of low immunogenicity, high tissue affinity, and low cost, and mEXO itself has anti-tumor effects. Hyaluronan (HA) naturally bind to CD44, a receptor which is highly expressed in LUAD tissues. This study aims to construct hyaluronan-modified milk exosome (HA-mEXO) and preliminarily investigate their molecular mechanisms for reversing PMX resistance through cellular experiments. METHODS: Exosomes were extracted from milk using high-speed centrifugation, and HA-mEXO was constructed. PMX-resistant A549 and PC-9 cell lines were treated with mEXO and HA-mEXO, respectively. CCK-8 assays, colony formation assays, Transwell assays, and flow cytometry were performed to evaluate proliferation, colony formation, migration, invasion, and apoptosis phenotypes in the treated resistant cell lines. Finally, transcriptomic sequencing, analysis, and cellular functional recovery experiments were conducted to investigate the mechanism by which HA-mEXO reverses PMX resistance in LUAD cells. RESULTS: The expression of CD44 in A549 and PC-9 LUAD drug-resistant cell lines was significantly higher than that in parental cells, and the uptake rate of HA-mEXO by drug-resistant cell lines was significantly higher than that of mEXO. Compared to the mEXO group, HA-mEXO-treated A549 and PC-9 resistant cells exhibited significantly reduced half maximal inhibitory concentration (IC50) values for PMX, markedly diminished clonogenic, migratory, and invasive capabilities, and a significantly increased proportion of apoptotic cells. Western blot analysis revealed that, compared to parental cells, A549 and PC-9 drug-resistant cells exhibited downregulated ZNF516 expression and upregulated ABCC5 expression. Immunofluorescence analysis revealed that HA-mEXO treatment downregulated ABCC5 expression in A549 and PC-9 drug-resistant cells compared to the PBS group, whereas co-treatment with HA-mEXO and ZNF516 knockdown showed no significant change in ABCC5 expression. CONCLUSIONS HA-mEXO carrying ZNF516 suppress ABCC5 expression, thereby enhancing the sensitivity of A549 and PC-9 LAUD drug-resistant cells to PMX.
Humans ; Hyaluronic Acid/chemistry* ; Drug Resistance, Neoplasm/drug effects* ; Exosomes/chemistry* ; Adenocarcinoma of Lung/genetics* ; Pemetrexed/pharmacology* ; Animals ; Lung Neoplasms/pathology* ; Milk/chemistry* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Hyaluronan Receptors/metabolism*

BACKGROUND: Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer morbidity and mortality worldwide, and its initiation and progression are closely associated with the tumor immune microenvironment. Increasing evidence suggests that environmental exposure is a critical factor influencing lung cancer development. Among these factors, fine particulate matter (PM2.5), a major component of air pollution, has been strongly linked to elevated lung cancer risk and unfavorable prognosis. However, the underlying immunoregulatory mechanisms by which PM2.5 drives LUAD progression remain poorly understood. Tumor-associated macrophages (TAMs), especially those polarized toward the M2 phenotype, are key components of the tumor microenvironment and play crucial roles in tumor growth, angiogenesis, and immune evasion. This study aims to investigate the effects of PM2.5 exposure on TAMs and to identify the key pro-tumorigenic factors mediating this process. METHODS: A mouse orthotopic lung cancer model under PM2.5 exposure was established to assess lung tumor growth and macrophage phenotypic alterations using in vivo imaging and flow cytometry. A subcutaneous tumor model involving co-inoculated macrophages and tumor cells was used to further verify the effects of PM2.5 on the function of TAMs and tumor malignancy. Combining in vitro experiments, flow cytometry, Western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, colony formation assay, and wound healing assay were employed to evaluate the regulatory effects of PM2.5 on the polarization of bone marrow-derived macrophages (BMDMs) as well as tumor cell proliferation, migration, and colony-forming ability. Transcriptome sequencing integrated with TISIDB (Tumor-immune System Interactions Database) and GEPIA (Gene Expression Profiling Interactive Analysis) databases was performed to identify key cytokines for further functional validation. RESULTS: In the mouse orthotopic lung cancer model, PM2.5 exposure significantly promoted tumor growth and increased the proportion of M2-type TAMs (P<0.05). Subcutaneous co-inoculation with PM2.5-treated BMDMs markedly enhanced tumor proliferation and elevated the intratumoral M2-type TAMs. PM2.5-pretreated BMDMs exhibited an immunosuppressive programmed cell death ligand 1 (PD-L1)+/arginase 1 (Arg1)+ phenotype, and their conditioned media significantly promoted proliferation, migration, and colony formation of Lewis lung carcinoma cells (LLC) and B16 melanoma cells (B16) (P<0.05). Transcriptome analysis revealed that PM2.5 substantially altered macrophage gene expression, with IL-1α identified as a key upregulated secreted cytokine enriched in immunosuppressive related signaling pathways. Clinical database analyses further indicated that IL-1α expression was positively correlated with macrophage and regulatory T cells (Treg) infiltration in the LUAD immune microenvironment, and that high IL-1α expression was associated with worse overall survival in LUAD patients (HR=1.5, P=0.0053). Western blot, RT-qPCR, and immunofluorescence confirmed that PM2.5 exposure significantly upregulated IL-1α expression and secretion in TAMs. CONCLUSIONS PM2.5 exposure facilitates LUAD progression by inducing an immunosuppressive phenotype in macrophages and enhancing the malignant behaviors of tumor cells. Mechanistically, IL-1α may serve as a key pro-tumorigenic cytokine secreted by macrophages under PM2.5 exposure. This study provides new insights into the pathogenesis of PM2.5-associated LUAD and suggests that IL-1α could serve as a potential therapeutic target.
Animals ; Mice ; Tumor-Associated Macrophages/immunology* ; Particulate Matter/toxicity* ; Adenocarcinoma of Lung/metabolism* ; Lung Neoplasms/genetics* ; Humans ; Disease Progression ; Tumor Microenvironment/drug effects* ; Cell Proliferation/drug effects* ; Cell Line, Tumor

OBJECTIVE: To explore the differences in perioperative clinical and pathological characteristics of patients with different pathological types of prostate cancer undergoing radical prostatectomy, and to analyze the influencing factors that may affect the extraglandular invasion of ductal adenocarcinoma of the prostate. METHODS: Retrospective collection was made of the radical prostatectomy patients who were admitted to Peking University Third Hospital from December 2011 to April 2021. The patients were screened based on inclusion criteria to obtain basic clinical features and postoperative pathological results. According to the pathological results, the patients were divided into ductal adenocarcinoma group (mixed with ductal adenocarcinoma) and acinar adenocarcinoma group, and a 1 ∶1 propensity score matching was performed to compare the differences in clinical characteristics between the two groups. Univariate and multivariate analyses of the factors related to extraglandular invasion were performed in the matched ductal adenocarcinoma groups. RESULTS: A total of 764 patients with prostate cancer were enrolled in this study, of which 62 patients were confirmed to have ductal adenocarcinoma components by postoperative pathology. There was a statistically significant difference in the proportion of the patients with a history of diabetes in baseline characteristics between the two groups before propensity score matching (29.5% vs. 17.7%, P=0.027). A total of 61 patients with simple acinar adenocarcinoma were successfully matched with the patients with ductal adenocarcinoma, and there was no statistically significant difference in baseline characteristics between the two groups after matching (P>0.05). The comparison of perioperative clinical and pathological features showed that International Society of Urology Pathology (ISUP) grade (P=0.003), pT stage (P=0.004), extraglandular invasion rate (P=0.018) and vascular thrombus rate (P=0.019) in ductal adenocarcinoma group were significantly higher than those in simple acinous adenocarcinoma group. Univariate analysis of the influence factors of extraglandular invasion showed that prostate-specific antigen (PSA) level, prostate volume, ISUP grade, seminal vesicle invasion and perineural invasion might be the influencing factors of extraglandular invasion (P < 0.10). Binary Logistic regression analysis showed that perineural invasion was an independent factor of extraglandular invasion (OR=11.78, 95%CI: 1.97-70.56, P=0.007). CONCLUSION Prostatic ductal adenocarcinoma has a worse prognosis than simple acinar adenocarcinoma. Perineural invasion is the influencing factor of extraglandular invasion of ductal adenocarcinoma.
Humans ; Male ; Prostatic Neoplasms/surgery* ; Retrospective Studies ; Prostatectomy ; Neoplasm Invasiveness ; Middle Aged ; Aged ; Carcinoma, Ductal/surgery* ; Propensity Score ; Adenocarcinoma/surgery*