Pathological Type Of Lung Cancer Research Articles

Polyphyllin I ameliorates gefitinib resistance and inhibits the VEGF/VEGFR2/p38 pathway by targeting HIF-1a in lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been administered as the first-line therapy for patients with EGFR mutations in LUAD, but it is almost inevitable that resistance to EGFR-TKIs therapy eventually arises. Polyphyllin I (PPI), derived from Paris polyphylla rhizomes, has been shown to have potent anti-cancer properties in a range of human cancer types including LUAD. However, the role of PPI in gefitinib resistance and the underlying mechanism remain elusive. PurposeTo evaluate the antitumor impacts of PPI on gefitinib resistance cells and investigate its molecular mechanism. MethodsCCK-8, wound healing, transwell assay, and xenograft model were performed to determine the anti-cancer effects of PPI as well as its ability to overcome gefitinib resistance. Immunoblotting, co-immunoprecipitation, phospho-RTK antibody array, qRT-PCR, and immunofluorescence were utilized to explore the mechanism by which PPI overrides gefitinib resistance. ResultsPPI inhibited cell survival, growth, and migration/invasion in both gefitinib-sensitive (PC9) and -resistant (PC9/GR) LUAD cells (IC50 at 2.0 μM). Significantly, treatment with PPI at 1.0 μM resensitized the resistant cells to gefitinib. Moreover, cell-derived xenograft experiments revealed that the combination of PPI and gefitinib overcame gefitinib resistance. The phospho-RTK array and immunoblotting analyses showed PPI significant inhibition of the VEGFR/p38 pathway. In addition, molecular docking suggested the interaction between PPI and HIF-1α. Mechanistically, PPI reduced the protein expression of HIF-1α in both normoxia and hypoxia conditions by triggering HIF-1α degradation. Moreover, HIF-1α protein but not mRNA level was elevated in gefitinib-resistant LUAD. We further demonstrated that PPI considerably facilitated the binding of HIF-1α to VHL. ConclusionsWe present a novel discovery demonstrating that PPI effectively counteracts gefitinib resistance in LUAD by modulating the VEGF/VEGFR/p38 pathway. Mechanistic investigations unveil that PPI facilitates the formation of the HIF-1α /VHL complex, leading to the degradation of HIF-1α and subsequent inhibition of angiogenesis. These findings uncover a previously unidentified mechanism governing HIF-1α expression in reaction to PPI, providing a promising method for therapeutic interventions targeting EGFR-TKI resistance in LUAD.

A liquid biopsy assay for the noninvasive detection of lymph node metastases in T1 lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer. The presence of lymph node metastasis plays a crucial role in determining the overall treatment approach and long-term prognosis for early LUAD, therefore accurate prediction of lymph node metastasis is essential to guide treatment decisions and ultimately improve patient outcomes. We performed transcriptome sequencing on T1 LUAD patients with positive or negative lymph node metastases and combined this data with The Cancer Genome Atlas Program cohort to identify potential risk molecules at the tissue level. Subsequently, by detecting the expression of these risk molecules by real-time quantitative PCR in serum samples, we developed a model to predict the risk of lymph node metastasis from a training cohort of 96 patients and a validation cohort of 158 patients. Through transcriptome sequencing analysis of tissue samples, we identified 11 RNA (miR-412, miR-219, miR-371, FOXC1, ID1, MMP13, COL11A1, PODXL2, CXCL13, SPOCK1 and MECOM) associated with positive lymph node metastases in T1 LUAD. As the expression of FOXC1 and COL11A1 was not detected in serum, we constructed a predictive model that accurately identifies patients with positive lymph node metastases using the remaining nine RNA molecules in the serum of T1 LUAD patients. In the training set, the model achieved an area under the curve (AUC) of 0.89, and in the validation set, the AUC was 0.91. We have established a new risk prediction model using serum samples from T1 LUAD patients, enabling noninvasive identification of those with positive lymph node metastases.

Causal relationships between mitochondrial proteins and different pathological types of lung cancer: a bidirectional mendelian randomization study.

An increasing number of studies point to an association between mitochondrial proteins (MPs) and lung cancer (LC). However, the causal relationship between MPs and LC remains unclear. Consequently, our study employed a bidirectional Mendelian randomization (MR) analysis to explore the causal association between MPs and different pathological types of LC. A two-sample MR study was performed using the genome-wide association study (GWAS) data publicly available. We applied the primary inverse variance weighted (IVW) method along with additional MR methods to validate the causality between MPs and different pathological types of LC. To ensure the robustness of our findings, sensitivity analyses were employed. Moreover, we performed a bi-directional MR analysis to determine the direction of the causal association. We identified a total of seven MPs had significant causal relationships on overall LC, lung squamous cell carcinoma (LUSC), and small cell lung carcinoma (SCLC). We found two MPs had significant associations with overall LC, four MPs had significant associations with LUSC, and four MPs had significant associations with SCLC. Additionally, an MP was found to have a nominal relationship with LUSC. Moreover, no causality was found between MPs and lung adenocarcinoma (LUAD). Bidirectional MR showed no reverse effect between identified MPs and different pathological types of LC. In general, our findings of this MR study suggest causal associations of specific MPs with overall LC, LUSC, and SCLC. However, no such causality was found in LUAD.

Ubiquitylation of RUNX3 by RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD. MEX3C and RUNX3 mRNA levels in the tissues of LUAD patients were determined using reverse transcription‑quantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry. Expression of apoptosis and epithelial–mesenchymal transition related proteins were determined using western blotting analysis. LUAD cells transfected with si-MEX3C were administered to mice subcutaneously to monitor tumor progression and metastasis. We found that MEX3C is strongly upregulated in LUAD tissue sections, and involved in proliferation and migration. A549 and H1299 cells had significantly higher levels of MEX3C expression compared to control HBE cells. Knockdown of MEX3C dramatically decreased cell proliferation, migration, and invasion, and accelerated apoptosis. Mechanistically, we demonstrate MEX3C induces ubiquitylation and degradation of tumor suppressor RUNX3. Moreover, RUNX3 transcriptionally represses Suv39H1, as revealed by RNA pull-down and chromatin immunoprecipitation assays. The in vivo mice model demonstrated that knockdown of MEX3C reduced LUAD growth and metastasis significantly. Collectively, we reveal a novel MEX3C-RUNX3-Suv39H1 signaling axis driving LUAD pathogenesis. Targeting MEX3C may represent a promising therapeutic strategy against LUAD.

Knockdown of MRPL35 promotes cell apoptosis and inhibits cell proliferation in non-small-cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) is a major pathological type of lung cancer. However, its pathogenesis remains largely unclear. MRPL35 is a regulatory subunit of the mitoribosome, which can regulate the assembly of cytochrome c oxidases and plays an important role in the occurrence of NSCLC.MethodsThe expression of MRPL35 in NSCLC was detected by tissue microarray and immunohistochemistry. H1299 cells were infected with lentivirus to knockdown MRPL35, and the cells were subjected to crystal violet staining to assess the results of colony formation assays. A549 cells were infected by lentiviral particles-expressing shMRPL35 or shControl, and then subcutaneously injected into nude mice. Tumorigenesis in mice was detected by in vivo imaging. The potential pathway of MRPL35 in NSCLC was assessed by Western blotting.ResultsMRPL35 was over-expressed in NSCLC tissue compared to para-cancerous and normal tissues. Knockdown of MRPL35 suppressed cell proliferation and decreased NSCLC progression both in vitro and in vivo. The possible molecular mechanisms were also clarified, which indicated that MRPL35 could be involved in cell apoptosis and proliferation by modulating the expression levels of CDK1, BIRC5, CHEK1, STMN1 and MCM2. Knockdown of MRPL35 activated p53 signaling pathway and inhibited cell cycle regulation.ConclusionsThe oncogenic role of MRPL35 in NSCLC was potentially mediated through the cell cycle regulatory genes such as BIRC5, STMN1, CDK1, CHEK1 and MCM2, as well as activation of P53 signaling pathway.

Quantitative analysis of endobronchial elastography combined with serum tumour markers of lung cancer in the diagnosis of benign and malignant mediastinal and hilar lymph nodes

Purpose: In malignant tumours, elastography and serum tumour markers have shown high diagnostic efficacy. Therefore, we aimed to quantitatively analyse the results of endobronchial elastography combined with serum tumour markers of lung cancer to accurately distinguish benign and malignant mediastinal and hilar lymph nodes.Methods: Data of patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node enlargement in our hospital between January 2018 and August 2022 were retrospectively collected. The characteristics of quantitative elastography and serum tumour markers were evaluated.Results: We enrolled 197 patients (273 lymph nodes). In the differential diagnosis of benign and malignant mediastinal and hilar lymph nodes, the stiffness area ratio (SAR), strain ratio (SR), and strain rate in lymph nodes were significant, among which SAR had the highest diagnostic value (cut-off value, 0.409). The combination of the four tumour markers had a high diagnostic value (AUC, 0.886). Three types of quantitative elastography indices combined with serum tumour markers for lung cancer showed a higher diagnostic value (AUC, 0.930; sensitivity, 83.5%; specificity, 89.3%; positive predictive value, 88.1%; negative predictive value, 85%) (p < 0.05). In the differential diagnosis of pathological types of lung cancer, different quantitative elastography indicators and serum tumour markers for lung cancer have different diagnostic significance for the differential diagnosis of lung cancer pathological types.Conclusion: The quantitative analysis of endobronchial ultrasound elastography combined with tumour markers can improve the diagnosis rate of benign and malignant mediastinal and hilar lymph nodes, help guide the puncture of false negative lymph nodes, and reduce the misdiagnosis rate.

Management of locally advanced non-small cell lung cancer: State of the art and future directions.

Lung cancer is the second most common and the deadliest type of cancer worldwide. Clinically, non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer; approximately one-third of affected patients have locally advanced NSCLC (LA-NSCLC, stage III NSCLC) at diagnosis. Because of its heterogeneity, LA-NSCLC often requires multidisciplinary assessment. Moreover, the prognosis of affected patients is much below satisfaction, and the efficacy of traditional therapeutic strategies has reached a plateau. With the emergence of targeted therapies and immunotherapies, as well as the continuous development of novel radiotherapies, we have entered an era of novel treatment paradigm for LA-NSCLC. Here, we reviewed the landscape of relevant therapeutic modalities, including adjuvant, neoadjuvant, and perioperative targeted and immune strategies in patients with resectable LA-NSCLC with/without oncogenic alterations; as well as novel combinations of chemoradiation and immunotherapy/targeted therapy in unresectable LA-NSCLC. We addressed the unresolved challenges that remain in the field, and examined future directions to optimize clinical management and increase the cure rate of LA-NSCLC.

Multi-omics analysis reveals PUS1 triggered malignancy and correlated with immune infiltrates in NSCLC.

Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer. In this study, multi-omics analysis revealed a significant increase of pseudouridine synthase 1 (PUS1) in NSCLC and the high expression of PUS1 was associated with shorter OS (Overall Survival), PFS (Progression Free Survival), and PPS (Post Progression Survival) of NSCLC patients. Clinical subgroup analysis showed that PUS1 may be involved in the occurrence and development of NSCLC. Besides, TIMER, ESTIMATE, and IPS analysis suggested that PUS1 expression was associated with immune cell infiltration, and the expression of PUS1 was significantly negatively correlated with DC cell infiltration. GESA analysis also indicated PUS1 may involve in DNA_REPAIR, E2F_TARGETS, MYC_TARGETS_V2, G2M_CHECKPOINT and MYC_TARGETS_V1 pathways and triggered NSCLC malignancy through MCM5 or XPO1. Furthermore, PUS1 may be a potential target for NSCLC therapy.

Identification of CLIC5 as a Prognostic Biomarker and Correlated Immunomodulator for Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common pathological types of lung cancer. The gene Chloride Intracellular Channel 5 (CLIC5) has an important role in neurophysiology, cardiovascular biology, and tumour biology. Here, we explored the prognostic value and immune infiltration of CLIC5 expression in LUAD patients. We extracted transcriptional LUAD data from The Cancer Genome Atlas (TCGA) and the University of Alabama Cancer Database to explore CLIC5 expression profiles and their relation to CLIC5 and clinicopathological parameters. The relationship between CLIC5 and survival time was explored using Kaplan-Meier Plotter. Then, we integrated the data from TCGA and the Gene Expression Omnibus (GEO) database to perform univariate and multivariate Cox regression. We performed CLIC5 immunohistochemical staining on 167 lung adenocarcinoma samples for further verification. In addition, we analysed the Gene Ontology (GO) database, Kyoto Encyclopaedia of Genes and Genomes pathways and network analysis of protein-protein interactions in lung tissue, to explore the potential mechanism of CLIC5. To analyse the correlation between immune infiltration and CLIC5 expression, we first compared the expression of immune cells in tumour tissues and normal tissues based on the TCGA and GEO databases. We found 51 immunomodulators related to CLIC5 and structured their enrichment pathways as well as those of 50 correlated genes. We used a Cox regression model to identify multiple-gene risk prediction signatures. Finally, we assessed the prognostic accuracy of the risk scores via receiver operating characteristic curves. CLIC5 expression levels were significantly lower in LUAD tissue than in normal tissue. Lower CLIC5 expression was negatively correlated to the overall survival of LUAD patients based on survival analysis. We identified CLIC5 as an independent prognosis predictor. Functional network analysis suggested that CLIC5 is related to multiple pathways. CLIC5 expression is closely related to infiltration levels of many immune cells and immune marker sets in LUAD patients. Furthermore, the risk score based on immunomodulators related to CLIC5 was an independent prognosis predictor in the TCGA lung cohorts. Our findings suggest that CLIC5 is a promising molecular marker for the prognosis and immune infiltration of LUAD patients.

Evaluating the Necessity of Adaptive RT and the Role of Deformable Image Registration in Lung Cancer with Different Pathologic Classifications.

This study aimed to analyze differential radiotherapy (RT) responses according to the pathological type of lung cancer to see the possibility of applying adaptive radiotherapy (ART). ART planning with resampled-computed tomography was conducted for a total of 30 patients (20 non-small-cell lung cancer patients and 10 small-cell lung cancer patients) using a deformable image registration technique to reveal gross tumor volume (GTV) changes according to the duration of RT. The small-cell lung cancer group demonstrated an average GTV reduction of 20.95% after the first week of initial treatment (p = 0.001), whereas the adenocarcinoma and squamous cell carcinoma groups showed an average volume reduction of 20.47% (p = 0.015) and 12.68% in the second week. The application of ART according to the timing of GTV reduction has been shown to affect changes in radiation dose irradiated to normal tissues. This suggests that ART applications may have to be different depending on pathological differences in lung cancer. Through these results, the present study proposes the possibility of personalized treatment options for individual patients by individualizing ART based on specific radiation responses by pathologic types of lung cancer.

Clinico-pathological characteristics of IGFR1 and VEGF-A co-expression in early and locally advanced-stage lung adenocarcinoma.

Although targeted therapies and immunotherapy have achieved significant clinical benefits in patients with certain pathological types of lung cancer. However, prognosis for patients with lung adenocarcinoma still remains unsatisfactory. It is of extremely importance to find ideal prognostic indicators to predict the prognosis of lung adenocarcinoma patients, especially for patients with early and locally advanced-stage lung adenocarcinoma. The purpose of this study is to elucidate the significance of Insulin-like growth factor receptor 1 (IGFR1) and Vascular endothelial growth factor A (VEGF-A) expression in predicting progression-free survival (PFS) and overall survival (OS) in patients with early and locally advanced-stage lung adenocarcinoma. In this study, IGFR1 and VEGF-A expression on 119 specimens of patients early and locally advanced-stage lung adenocarcinoma were analyzed by immunohistochemistry with an H-score system. Both high IGFR1 expression and VEGF-A expression patients were resulted in 59 (49.6%) separately. The numbers and proportions of IGFR1-&VEGF-A- subgroup, IGFR1-&VEGF-A+ subgroup, IGFR1+&VEGF-A- subgroup and IGFR1+&VEGF-A+ subgroup are 23 (19.3%), 37 (31.1%), 37 (31.1%) and 22 (18.5%) respectively. High IGFR1 expression was significantly associated with both poor PFS and OS of all patients in a univariate analysis. Multivariable analysis showed that patients with IGFR1+&VEGF-A+ expression exhibited a worst PFS and OS in the subgroup of lung adenocarcinoma patients with EGFR mutation. These results suggest that IGFR1+&VEGF-A+ is expected to be a disadvantageous factor for prognosis in the subgroup of EGFR mutation in patients with early and locally advanced-stage lung adenocarcinoma. What's more, this study may provide the theoretical possibility to screen optimal population for a combination therapy with anti-VEGF and anti-IGFR1 in patients with early and locally advanced-stage lung adenocarcinoma.

Prominin 2 decreases cisplatin sensitivity in non-small cell lung cancer and is modulated by CTCC binding factor.

Non-small cell lung cancer (NSCLC) is the major pathological type of lung cancer and accounts for the majority of lung cancer-related deaths worldwide. We investigated the molecular mechanism of prominin 2 (PROM2) involved in cisplatin resistance in NSCLC. The GEO database was analyzed to obtain differential genes to target PROM2. Immunohistochemistry and western blotting were used to detect protein expression levels. To examine the role of PROM2 in NSCLC, we overexpressed or knocked down PROM2 by transfection of plasmid or small interfering RNA. In functional experiments, CCK8 was used to detect cell viability. Cell migration and invasion and apoptosis were detected by transwell assay and flow cytometry, respectively. Mechanistically, the regulation of PROM2 by CTCF was detected by ChIP-PCR. In vivo experiments confirmed the role of PROM2 in NSCLC. GEO data analysis revealed that PROM2 was up-regulated in NSCLC, but its role in NSCLC remains unclear. Our clinical samples confirmed that the expression of PROM2 was markedly increased in NSCLC tissue. Functionally, Overexpression of PROM2 promotes cell proliferation, migration and invasion, and cisplatin resistance. CTCF up-regulates PROM2 expression by binding to its promoter region. In vivo experiments confirmed that PROM2 knockdown could inhibit tumor growth and increase the sensitivity of tumor cells to cisplatin. PROM2 up-regulation in NSCLC can attenuate the sensitivity of NSCLC cells to cisplatin and promote the proliferation, migration and invasion of tumor cells. PROM2 may provide a new target for the treatment of NSCLC.

Disruption of Iron Homeostasis to Induce Ferroptosis with Albumin-Encapsulated Pt(IV) Nanodrug for the Treatment of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)-based drugs are still one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt-based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin-encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi-omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application.

Comparison between different treatment regimens of vascular targeting drug to malignant pleural effusion in patients with lung cancer: A Bayesian network meta-analysis.

The presence of malignant pleural effusion in lung cancer patients often suggests a poor prognosis. We plan to investigate which regimen of vascular targeting drug is preferable to control the malignant pleural effusion in such patients. Two investigators dependently searched and screened for randomized controlled trials in PubMed, Embase, Web of Science and China National Knowledge Infrastructure from the database inception to August 2022. R software was applied to build a network model in Bayesian method. Objective response rate of malignant pleural effusion is the primary outcome measure. Besides, the incidence of 3 adverse events were compared, including gastrointestinal reaction, leukopenia and hypertension. Due to the disconnection of network, we analysis and discuss the short-term treatment (3-4 weeks) and long-term treatment (6-12 weeks) respectively. 31 studies with 2093 patients were identified. Four targeting drugs contain bevacizumab (Bev), anlotinib, apatinib and Endostar. Two administration routes include intracavity perfusion (icp) and intravenous injection. Based on the current evidence, for short-term treatments, compared with single-agent chemotherapy (CT), Bev_icp + CT, anlotinib + CT, Bev_icp and anlotinib + endorstar_icp present better objective response, and no statistical significance was found in objective response between Bev_icp + CT, anlotinib + CT and Bev_icp. For long-term treatments, compared with doublet or triplet chemotherapy (2CT or 3CT), Bev_icp + 2CT, apatinib + 2CT, Bev_icp + 3CT, and Bev_intravenous injection + 2CT are more effective option, but no statistical significance was found in objective response between the 4 combination regimens with chemotherapy. Our findings suggest that no statistical significance between above vascular targeting regimens. Pathological type of lung cancer may affect the effect of bevacizumab intracavity infusion plus chemotherapy. The influence of different administration routes of vascular targeting drugs on efficacy remains to be investigated. There are some concerns with the quality of the studies, and some limitations should be considered when interpreting these results, which includes limited geographical region and sample size of studies. Despite these limitations, this study may inform vascular targeting therapy choice in such a patient population.

To explore the effect of kaempferol on non-small cell lung cancer based on network pharmacology and molecular docking.

Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.

A case report of refractory pulmonary adenocarcinoma

As one of the most common types of carcinomas, lung cancer has high incidence and mortality rates. Among the pathological types of lung cancer, pulmonary adenocarcinoma is the most prevalent. Advancements in medical treatments have contributed to improved prognosis in pulmonary adenocarcinomas. However, this case report revealed a rare refractory lung adenocarcinoma, suggesting that further research and robust management strategies are needed to improve clinical outcomes. In this regard, 18F-fluorodeoxyglucose positron emission tomography/ computed tomography plays a very important role in the comprehensive evaluation of glucose metabolic activity in lung adenocarcinoma and the progression of metastasis in distant organs.

Prediction of distant organ metastasis and overall survival of lung cancer patients: a SEER population-based cohort study.

Distant organ metastasis is a common event in lung cancer (LC). However, the preferential metastatic pattern of different pathological types of LC and its effect on prognosis have not been comprehensively elucidated. This study aimed to explore the distant metastasis pattern and construct nomograms predicting the metastasis and survival of LC patients using the Surveillance, Epidemiology, and End Results (SEER) database. LC data were downloaded from the SEER database to conduct logistic regression and investigate risk factors for developing organ metastasis. A Cox regression analysis was conducted to investigate prognostic factors of LC. A Kaplan-Meier analysis was used to estimate overall survival outcomes. Nomograms were constructed to predict the probability of organ metastasis and the 1-, 3- and 5-year survival probability of LC patients. Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of the nomograms. All statistical analyses were conducted within R software. The liver is the most common metastatic organ of small cell carcinoma. The brain is the most likely metastasis site of large cell carcinoma, and bone is the most likely metastasis site for squamous cell carcinoma and adenocarcinoma. Patients with triple metastases (brain-bone-liver) have the worst prognosis, and for nonsquamous carcinoma with single organ metastasis, liver metastases conferred the worst prognosis. Our nomograms based on clinical factors could predict the metastasis and prognosis of LC patients. Different pathological types of LC have different preferential metastatic sites. Our nomograms showed good performance in predicting distant metastasis and overall survival. These results will provide a reference for clinicians and contribute to clinical evaluations and individualized therapeutic strategies.

Correlation between HRCT signs and levels of CA125, SCCA, and NSE for different pathological types of lung cancer.

The aim of this study was to investigate the correlation between high-resolution CT (HRCT) signs and serum tumor markers, to improve the diagnostic level and identify different pathological types of lung cancer. 102 patients with pathologically confirmed lung cancer were selected as the observation group. HRCT scan and serum tumor markers [cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCCA), and neuron-specific enolase (NSE)] were performed to analyze the correlation. Among the 102 cases of lung cancer, 88 cases were of lobulation sign, 78 cases of speculation sign, 45 cases of pleural indentation sign, 35 cases of vessel tracking sign, and 34 cases of vacuole sign. CA125 had the highest concentration in lung adenocarcinoma (55.74±14.18) ng/ml, and SCCA had the highest concentration in lung squamous cell carcinoma (18.98±6.37) ng/ml. The concentration of NSE in small cell lung cancer was the highest (48.12±16.19) ng/ml. Pleural indentation sign and vacuole sign were more likely to happen in lung adenocarcinoma and lung squamous cell carcinoma, respectively. The significant increase of CA125, SCCA, and NSE concentrations suggested that lung cancer patients were more likely to suffer from lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer, respectively.

Abstract 5054: The study of synergy mechanism between surufatinib and vinorelbine in the treatment of non-small cell lung cancer

Abstract Background: The incidence and mortality rate of lung cancer ranks first among malignant tumors. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Combined use of targeted therapy can enhance the efficacy of chemotherapy drugs while reduce the related side effects in clinical practice. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI), selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, Fibroblast growth factor receptor 1 (FGFR1), and CSF-1R, which simultaneously prevents tumor angiogenesis and tumor immune evasion. Our clinical study (NCT04922658) has showed the promising effect and safety of surufatinib plus vinorelbine in NSCLC patients, but the potential mechanism is still to be revealed. Herein, tumor-bearing models and cancer cell culture platform would be established for further studying, which may shed light on the synergy mechanism between surufatinib and vinorelbine, and guide the clinical treatment ultimately. Methods: Subcutaneous tumorigenesis in nude mice were successfully established, and then treated with related experimental drugs. The tumor size was observed and CD31 expression of tumor tissue was measured using immunohistochemical analysis. In vitro study, the A549 and PC9 cell multiplication capacities were measured by CCK8 assay and plate cloning assay. The abilities of cancer cell migration and apoptosis were detected using cell scratch assay and flow cytometry kit, respectively. Results: Monotherapy with surufatinib or vinorelbine showed a moderate tumor suppression, whereas the combination therapy of surufatinib and vinorelbine showed the remarkable inhibition of tumor growth in vivo. Surufatinib and the combination therapy obviously decreased the expression of CD31 in tumor issue which might cause the anti-angiogenesis. Monotherapy with surufatinib or vinorelbine significantly inhibited the proliferation of lung cancer cells (A549 cells and PC9 cells) in a concentration-dependent manner, and surufatinib could memorably promote the anti-proliferation activity of vinorelbine. As a result, combination therapy of surufatinib and vinorelbine distinctly inhibited lung cancer cell proliferation when compared with monotherapy with vinorelbine. Consistently, the synergistic effects of surufatinib plus vinorelbine were also observed in cell migration and apoptosis analysis. Conclusions: Synergistic effect of surufatinib and vinorelbine resulted in a conspicuous tumor regression, which is consistent with the clinical observation. In a depth data analysis, surufatinib enhanced the antitumor activity of vinorelbine probably by inhibiting tumor cell proliferation and migration, suppressing tumor angiogenesis and promoting tumor apoptosis in NSCLC patients. Citation Format: Xiaoran Wu, Yanfang Zheng, Lingyu Qin, Ying Li, Zhongjian Yu, Xiongjie Zhu, Rui Cai, Feiyu Niu, Yan Yuan, Peng Jiang, Shaoshi Wen, Xing Lv, Jiancai Zhou. The study of synergy mechanism between surufatinib and vinorelbine in the treatment of non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5054.

Association between idiopathic pulmonary fibrosis and risk of different pathological types of lung cancer: a Mendelian randomization study.

Many epidemiological studies have shown that idiopathic pulmonary fibrosis (IPF) is a risk factor for lung cancer (LC), but these studies do not provide direct evidence of a causal association between the two diseases. We investigated the causal association between IPF and different pathological types of LC based on the Mendelian randomization (MR) study. The genome-wide association study (GWAS) data of IPF and LC were obtained from the latest published articles, and instrumental variables (IVs) for analysis were obtained after screening and eliminating the confounders. MR Analysis was carried out with the help of random effects inverse variance weighting (re-IVW), MR-egger, and weighted median method, and a comprehensive sensitivity test was conducted. The results of re-IVW analysis showed that IPF may increase the risk of lung squamous cell carcinoma (LUSC) (OR = 1.045, 95% CI 1.011 to 1.080, P = 0.008). In addition, no causal relationship was found between IPF and overall LC (OR = 0.977, 95% CI 0.933 to 1.023, P = 0.32), lung adenocarcinoma (LUAD) (OR = 0.967, 95% CI 0.903 to 1.036, P = 0.345) and small cell lung carcinoma (SCLC) (OR = 1.081, 95% CI 0.992 to 1.177, P = 0.074). A comprehensive sensitivity analysis ensured the reliability of the study. In conclusion, from the perspective of genetic association, we found that IPF is an independent risk factor for LUSC and may increase the risk of LUSC, but no such causal relationship was found in LUAD and SCLC.