Non-small Cell Lung Cancer Group Research Articles

Serum CYFRA 21-1 as a Prognostic Marker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background: A prognostic marker in patients with non-small-cell lung cancer (NSCLC) treated with anti-PD-1/PD-L1 antibodies must be established. This study explored serum cytokeratin fraction 21-1 (CYFRA 21-1), which represents a squamous cell histology, as a prognostic factor in anti-PD-1/PD-L1 antibody treatment, stratifying by histology and treatment regimen. Methods: This study retrospectively evaluated patients with advanced NSCLC without driver mutations receiving anti-PD-1/PD-L1 antibodies between November 2015 and March 2023. Cutoff values for CYFRA 21-1 and carcinoembryonic antigen (CEA) were 3.5 and 5.0 ng/mL, respectively. The Kaplan-Meier method and a log-rank test were conducted. The Cox proportional hazards model was utilized for univariate and multivariate analyses. Results: This study included 258 patients. The squamous NSCLC group demonstrated a shorter overall survival (OS) than the non-squamous NSCLC group (median, 17.8 vs. 23.7 months, p = 0.141). Patients with high serum CYFRA 21-1 and CEA levels exhibited a significantly shorter OS than those with normal levels (median, 11.7 vs. 32.7 months, p < 0.005; 15.8 vs. 29.7 months, p < 0.005). The multivariate analysis identified a performance status (PS) of ≥2, a PD-L1 expression of ≥50%, and a serum CYFRA 21-1 of >3.5 ng/mL as independent prognostic factors. Patients with high serum CYFRA 21-1 levels exhibited a significantly shorter OS even focusing on non-squamous NSCLC, anti-PD-1/PD-L1 antibody and chemotherapy combination therapy, or anti-CTLA-4 antibody combination therapy. Conclusion: Serum CYFRA 21-1 is a poor prognostic marker for patients with NSCLC receiving anti-PD-1/PD-L1 antibody treatment even when stratifying by histology or treatment regimen.

Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.

An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.

Diagnostic value of microRNA-200 expression in peripheral blood-derived extracellular vesicles in early-stage non-small cell lung cancer

ObjectiveThis study assessed the diagnostic value of microRNA-200 (miR-200) expression in peripheral blood-derived extracellular vesicles (EVs) in early-stage non-small cell lung cancer (NSCLC).MethodsThis study retrospectively analyzed 100 healthy volunteers (the control group) receiving physical examinations, 168 early-stage NSCLC patients (the NSCLC group), and 128 patients with benign lung nodules (the benign group). The basic and clinical data of participants were obtained, including age, sex, smoking history, carbohydrate antigen 242 (CA242), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), forced expiratory volume in 1 s, maximal voluntary ventilation, forced vital capacity, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and miR-200 expression. The correlation of miR-200 expression in peripheral blood-derived EVs with CA242, CEA, and CA199 was analyzed, and the diagnostic value of peripheral blood-derived EV miR-200 for early-stage NSCLC was assessed. The risk factors of early-stage NSCLC development were also determined.ResultsAge, the percentage of patients with smoking history, CA242, CEA, CA199, IL-6, and TNF-α levels, and miR-200 expression in peripheral blood-derived EVs were significantly higher in the NSCLC group than in the benign and control groups. Lung disease patients with high miR-200 expression in peripheral blood-derived EVs comprised a higher percentage of patients with smoking history and mixed lesions and had higher CA242, CEA, CA199, and TNF-α levels than those with low miR-200 expression in peripheral blood-derived EVs. In lung diseases, miR-200 expression in peripheral blood-derived EVs was significantly and positively correlated with CA242, CEA, and CA199. Peripheral blood-derived EV miR-200 combined with CA242, CEA and CA199 had higher diagnostic value (area under the curve = 0.942) than single detection, along with higher specificity, and high expression of peripheral blood-derived EV miR-200 was an independent risk factor for early-stage NSCLC.ConclusionPeripheral blood-derived EV miR-200 expression in patients with lung diseases is closely correlated with CA242, CEA, and CA199, and high expression of peripheral blood-derived EV miR-200 is an independent risk factor for early-stage NSCLC and is of high clinical diagnostic value for early-stage NSCLC.

A phase II study of weekly carboplatin and concurrent radiotherapy in older adults with locally advanced non-small cell lung cancer (LOGIK1902).

Concurrent chemoradiotherapy is the standard therapy for locally advanced non-small cell lung cancer (NSCLC). However, there is little evidence supporting its use in older adults. Low-dose daily carboplatin combined with thoracic radiotherapy is considered a standard regimen for this population. To establish a simple and feasible carboplatin administration method, we conducted a study of weekly carboplatin and concurrent radiotherapy for older adults with locally advanced NSCLC. This prospective, single-arm, multicenter, phase II clinical trial included patients aged ≥75 years with unresectable stage III NSCLC and Eastern Cooperative Oncology Group performance status 0-1. Patients received chemoradiotherapy (60 Gy/30 fractions plus concurrent weekly carboplatin at an area under curve of 2 mg mL-1 min-1). The primary endpoint was the overall response rate (ORR). Key secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. From July 2020 to June 2022, 37 patients were enrolled from 15 institutions, and 36 patients were evaluable for efficacy and safety. The ORR was 63.9% (95% confidence interval [CI] = 47.6-77.5). Median PFS was 14.6 months (95% CI = 9.1-18.1). Median OS was 25.5 months (95% CI = 17.4-not reached). Grade 4 leucopenia, neutropenia, and thrombocytopenia were observed in one patient (2.8%) each. Weekly carboplatin and concurrent radiation therapy was safe in older adults with locally advanced NSCLC, and promising activity was observed.

The role of leptin, resistin, and irisin levels as prognostic indicators of lung cancer in Iraqi patients

ABSTRACT Lung cancer is the most lethal malignancy and is often associated with a poor prognosis because of a lack of prognostic markers. Thus, this study aimed to determine whether irisin, resistin, and leptin could be useful biomarkers for lung cancer prognosis. The study is designed on 100 lung cancer patients, (66) patients with non-small cell lung cancer (NSCLC) and (34) patients with small cell lung cancer (SCLC). For the purpose of comparison, (66) samples as control group. Using the ELISA technique to estimate leptin, resistin, and irisin levels in patients and controls. The results indicate a significant increase in mean leptin in NSCLC and SCLC groups (10.71 ± 0.30 and 10.13 ± 0.51) ng/ml, respectively, in contrast to the control (8.26 ± 0.47) ng/ml. The mean of irisin and resistin had been significantly increased in SCLC group (5.86 ± 0.13 pg/ml and 7.25 ± 0.38 ng/ml, respectively) and NSCLC group (5.08 ± 0.09 pg/ml and 6.35 ± 0.13 ng/ml, respectively) in contrast to the control (4.13 ± 0.09 pg/ml and 3.96 ± 0.17 ng/ml, respectively). The higher levels of leptin in NSCLC patients could serve as a prognostic marker for NSCLC. The variations in Resistin and Irisin levels across different stages of lung cancer suggest that they might be useful in predicting the prognosis of lung cancer.

Detection of PD‑L1 expression and epithelial‑mesenchymal transition of circulating tumor cells in non‑small cell lung cancer.

The present study aimed to assess the roles of peripheral circulating tumor cell (CTC) count, CTC subtypes and programmed death ligand 1 (PD-L1) expression in the clinical staging and prognosis of patients with non-small cell lung cancer (NSCLC). A total of 100 patients with NSCLC with available tumor tissues were enrolled in the present study, and 7.5 ml peripheral blood was collected. Patients were divided into PD-L1-positive and PD-L1-negative groups according to PD-L1 immunohistochemical staining. Peripheral blood samples from both groups were analyzed to determine the CTC count, epithelial-type CTCs (E-CTCs), mesenchymal-type CTCs (M-CTCs) and PD-L1 expression. Clinical data were collected, and patients were followed up for a maximum of 36 months, with patient death as the endpoint event. Patients with PD-L1-positive tumors had a worse prognosis compared with those with PD-L1-negative tumors (P=0.045). The PD-L1-positive group exhibited significantly higher numbers of CTCs and M-CTCs compared with the PD-L1-negative group (P≤0.05). However, the number of E-CTCs did not differ significantly between the two groups (P>0.05). PD-L1-positive patients with higher CTC and M-CTC counts had relatively poorer prognoses (P≤0.05), while the number of E-CTCs had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the CTC count (P≤0.05), while E-CTC and M-CTC counts did not significantly differ between the two groups (P>0.05). The PD-L1-positive group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs compared with the PD-L1-negative group (P≤0.05), while PD-L1+ E-CTC counts did not differ significantly between the two groups (P>0.05). The PD-L1-positive patients with a higher number of PD-L1+ CTCs and PD-L1+ M-CTCs had relatively poorer prognoses (P≤0.05), while the PD-L1+ E-CTC count had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs (P≤0.05), while PD-L1+ E-CTC counts did not significantly differ between the two groups (P>0.05). Based on univariate and multivariate analyses, the number of PD-L1+ M-CTCs was identified as an independent prognostic factor for NSCLC. In conclusion, the presence of CTCs in peripheral blood, particularly PD-L1+ M-CTC subtype, indicated poorer clinical staging and prognosis in patients with NSCLC. These findings suggested that CTCs, specifically the PD-L1+ M-CTC subtype, could serve as a monitoring indicator for the clinical staging and prognosis of patients with NSCLC.

Study on the difference and regularity of tongue images in 309 patients with different pathological stages of non-small cell lung cancer.

Tongue diagnosis is a crucial traditional Chinese medicine (TCM) inspection method for TCM syndrome differentiation and treatment. The primary research focus was on tongue image characteristic parameters of patients with non-small cell lung cancer (NSCLC). Analysis of the tongue image parameters of various pathological stages of NSCLC provides technical support for establishing an integrated Chinese and Western auxiliary diagnosis and efficacy evaluation medicine system for lung cancer that integrates tongue image features. Tongue image characteristics of 309 patients with NSCLC and 206 controls were collected and analyzed clinically. The T-test or rank sum test and logistic regression analysis were applied to analyze the characteristics of tongue image indicators of different pathological stages of NSCLC. There were differences in tongue image characteristics in the NSCLC group compared to the control group. The tongue quality and brightness of the tongue coating in the NSCLC group increased, the red component was reduced, the tongue coating thickened, and the yellow component increased compared to the healthy control group. A comparison of tongue image indexes of NSCLC in different pathological stages showed that stage IV had lower TB-b and higher TB-a than stage I. In addition, stage IV had lower TB-b than stage II + III, showing an increase in the blue and red components of the tongue in stage IV and the appearance of cyanotic tongue features. The tongue image characteristics of NSCLC patients differed from those of the control group. Tongue imaging indicators can reflect the characteristics of tongue images of patients with NSCLC. The tongue image characteristics of patients with stage IV lung cancer are bluish and purple compared with those with stage I, II, and III. It is suggested that the tongue's image characteristics can be used as a reference for the pathological classification of NSCLC and judgment of the disease process.

First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy.

The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.

Gut microbiota and its metabolites in non-small cell lung cancer and brain metastasis: from alteration to potential microbial markers and drug targets.

The elevated mortality rate associated with non-small-cell lung cancer (NSCLC) is a well-established global concern. Considerable attention has been directed toward exploring the association between gut microbiota and various malignant tumors. We herein investigated the associations between the intestinal microbiome and its metabolites, particularly short-chain fatty acids (SCFAs), in patients with NSCLC at different stages, including early and brain metastasis (BM) stages. The findings aim to offer a fresh perspective on the diagnosis and management of NSCLC. Fecal samples were collected from 115 participants, comprising healthy controls (n = 35) and patients with treatment-naive NSCLC at the early stage (ELC, n = 40) and the BM stage (n = 40). Characterization of the intestinal microbiome and fecal SCFA levels was performed using 16S rRNA gene sequencing and gas chromatography. The microbial diversity in patients with NSCLC was found to be less abundant and uniform, particularly in the BM stage. Significant alterations in the community structure of the gut microbiota were observed in patients with NSCLC, with an increase in pathogens in Fusobacteria and Proteobacteria and a decrease in SCFA-producing bacteria in Firmicutes and Actinobacteria, particularly in the BM stage. Meanwhile, microbial communities displayed intricate associations in patients with NSCLC. A biomarker panel (Faecalibacterium, Bifidobacterium, Butyricicoccus, Klebsiella, Streptococcus, and Blautia) successfully distinguished patients in the ELC and BM stages from healthy controls (area under the curve: 0.884). The overall concentration of fecal SCFAs was significantly lower in patients with BM compared to patients with ELC and healthy controls. Subgroup analysis of acetate and butyrate yielded similar results. Moreover, multiple disrupted pathways in the NSCLC group were identified using the Kyoto Encyclopedia of Genes and Genomes annotation, including lipid metabolism and genetic information processing, specifically in the BM stage. Compared with healthy controls, distinct host-microbe interactions were evident in different phases of patients with NSCLC. Furthermore, specific forms of the gut microbiome and SCFAs may serve as valuable biomarkers and therapeutic targets in the diagnosis and treatment of NSCLC.

The Diagnostic and Prognostic Value of the Combination of Tumor M2-Pyruvate Kinase, Carcinoembryonic Antigen, and Cytokeratin 19 Fragment in Non-Small Cell Lung Cancer.

Objective: Finding biomarkers related to non-small cell lung cancer (NSCLC) is helpful for the diagnosis and precise treatment of lung cancer. The relationship between serum tumor M2-pyruvate kinase (TuM2-PK), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment (CYFRA21-1) and NSCLC was analyzed. Methods: The serum levels of TuM2-PK, CEA, and CYFRA21-1 in 184 patients with the NSCLC group, 60 patients with the benign lung disease (BLD) group, and 90 healthy controls (HC) group were detected. The levels of TuM2-PK were measured by using an enzyme-linked immunosorbent assay. The detection methods of CEA and CYFRA21-1 were electrochemiluminescence. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of TuM2-PK, CEA, and CYFRA21-1 on NSCLC. The Kaplan-Meier survival curve was drawn to evaluate the survival status in NSCLC patients with different serum levels of TuM2-PK, CEA, and CYFRA21-1. Results: Serum levels of TuM2-PK, CEA, and CYFRA21-1 in the NSCLC group were significantly higher than those in the BLD group and the HC group (P < .01). Serum levels of TuM2-PK, CEA, and CYFRA21-1 in NSCLC patients were associated with the tumor lymph node metastasis stage (P < .05), lymph node metastasis (P < .05), and distant metastasis (P < .05). The ROC curve showed that the area under the curve of serum levels of TuM2-PK, CEA, and CYFRA21-1 was 0.814, 0.638, and 0.719, respectively, and that the combination of the above 3 was 0.918. The Kaplan-Meier survival curve showed that the 1-, 3- and 5-year survival rate in NSCLC patients with positive TuM2-PK, CEA, and CYFRA21-1 was significantly lower than that in NSCLC patients with negative TuM2-PK, CEA, and CYFRA21-1, respectively (P < .05). Conclusions: Serum TuM2-PK, CEA, and CYFRA21-1 levels have high clinical values in the diagnosis of NSCLC, and can effectively judge the prognosis of patients.

Effect of thymalfasin on myeloid-derived suppressor cells in patients with non-small cell lung cancer.

To observe the effect of thymalfasin on myeloid-derived suppressor cells (MDSCs) subsets in peripheral blood of patients with non-small cell lung cancer (NSCLC). 50 cases of NSCLC (NSCLC group) diagnosed in Chest Hospital of Jiangxi Province were selected as the research subjects, and 50 healthy subjects who underwent physical examination in our hospital during the same period were selected as the healthy control group. The expression of HLA-DR-CD14-CD33+ MDSCs in peripheral blood mononuclear cells and tumor tissue single cell suspension of NSCLC patients before and after thymalfasin treatment was explored by flow cytometry. The proportion of MDSCs in peripheral blood of NSCLC group was 1.70±0.52%, which was significantly higher than that in peripheral blood (0.51±0.15%) of healthy controls (P < 0.05). The proportion of HLA-DR-CD14-CD33+ MDSCs in the tissues of NSCLC group was 1.65±0.43% before treatment and 1.15±0.50% after treatment (P < 0.05). The proportion of MDSCs in peripheral blood of NSCLC patients before treatment was 1.70±0.52%, and that after treatment was 0.59±0.18% (P < 0.05). Thymalfasin can reduce the number of MDSCs in peripheral blood mononuclear cells. The application of thymalfasin in the treatment of NSCLC patients can help to enhance the anti-tumor effect.

Dissecting the Clinical Characteristics and Treatment Outcomes Correlates of KRAS G12C-Mutated Non-Small Cell Lung Cancer.

KRAS mutation is one of the most common driver oncogenes in non-small cell lung cancer (NSCLC), and the most common mutation subtype is G12C. However, there is still a lack of efficacy and prognosis data related to immunotherapy, which hinders the promotion of new strategies. Clinical characteristics and treatment outcomes were collected and analyzed for patients with NSCLC harboring KRAS mutations at West China Hospital of Sichuan University from June 2013 to March 2023. Among the 231 patients with KRAS-mutated NSCLC, 29.4% had KRAS G12C mutations. Compared to the KRAS non-G12C NSCLC group, the KRAS G12C NSCLC group had a greater number of pack-years. The programmed death ligand 1 expression and the proportion of patients with a high tumor mutational burden were not significantly different between the two groups. Similar patterns of TP53, STK11, and CDKN2A mutations were observed between KRAS G12C and KRAS non-G12C NSCLC groups. The median progression-free survival (PFS) (8.4 vs 7.0 months, p=0.100) and overall survival (OS) (12.1 vs 18.1 months, p=0.590) were not statistically different between KRAS G12C and KRAS non-G12C. Compared to patients with KRAS G12C NSCLC who did not receive immunotherapy, patients who received immunotherapy had a better objective response rate (46.2% vs 0%, p=0.002), PFS (12.2 vs 7.5 months, p=0.087) and OS (49.9 vs 11.1 months, p=0.12). Patients with KRAS G12C were more likely to be smokers. Advanced KRAS G12C NSCLC patients who received immunotherapy had a better ORR than those who did not, suggesting that patients with G12C mutations are more likely to benefit from immunotherapy.

The assessment of Dickkopf-1 and Dickkopf-2 protein concentration in different subtypes of non-small cell lung cancer subtypes.

Lung cancer is one of the most prevalent cancers worldwide. Dickkopf-1 (DKK-1) and -2 (DKK-2) are important proteins for the regulated Wnt signalling pathway. Alternations in the Wnt pathway are associated with tumour progression. The aim of the study was to analyse the concentration of DKK-1 and DKK-2 in tumour and matched non-tumour (NT) samples of 65 patients with non-small cell lung cancer (NSCLC), including 3 subtypes: adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). The protein concentration was measured by enzyme-linked immunosorbent assay (ELISA) in homogenates. The difference between the level of DKK-1 in tumour and NT specimens was not significant for the whole NSCLC group and SCC and LCC subtype, while in AC samples they were significantly higher (p = 0.028). The highest concentration of DKK-1 was found in the advanced NSCLC samples, with the T4 parameter as well as stage III. Significantly decreased DKK-2 concentrations were detected in all NSCLC subtypes (p < 0.05). Moreover, the DKK-2 level was higher in non-smokers than in smokers. The results indicate that concentrations of DKKs were different in relation to subtypes as well as clinical and socio-demographic parameters. The concentration of DKKs could be associated with the progression of NSCLC. We suggest that DKK-1 could play an oncogenic role in AC, while DKK-2 could be a tumour suppressor in all NSCLC subtypes. Dickkopf-1 and DKK-2 proteins could have differential roles in the Wnt signalling pathway, which is important in many cellular processes, such as proliferation and apoptosis.

The importance of biglycan, decorin and TGF-1 levels in the diagnosis of non-small cell lung cancer

BACKGROUND: Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. METHODS: Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. RESULTS: The median age was 65(39–83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p= 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p= 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p= 0.002). In the multivariate regression analysis; Decorin &lt; 8.13 ng/mL (OR, 10.96; 95% CI: 3.440–34.958), current smoking (OR, 3.81; 95% CI: 1.320–10.998), COPD (OR, 43.6; 95% CI: 2.082–913.081), and lower BMI (OR, 1.22; 95% CI: 1.070–1.405, p= 0.003) were identified as independent predictive markers for NSCLC diagnosis. CONCLUSION: The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment.

CCR5 promoter polymorphisms associated with nonsmall cell lung cancer.

C-C chemokine receptor 5 (CCR5) plays a crucial role in the regulation of immune cell activation and migration as well as the progression of many cancers. We performed an in silico analysis using public data resources and found that the lung cancer patients with higher CCR5 expression had a notably better overall survival than those with lower CCR5 expression patients and CCR5 expression level is positive correlated with the infiltration of immune cells, such as B, CD8+ T and CD4+ T cells, in both lung adenocarcinoma and lung squamous cell cancer. In the present study, we investigated the association between the promoter polymorphism of CCR5 and nonsmall cell lung cancer (NSCLC). A case-control study of 449 NSCLC patients and 516 controls of Chinese Han population was conducted, along with polymorphism detection using a sequencing method. A dual-luciferase reporter assay system was used to analyse the transcriptional activity of CCR5 promoter variations. Our results showed that the frequency of rs1799987-AA was significantly higher in the NSCLC group than in the controls in recessive model (p=.007, OR=1.66 95% confidence interval [CI]: 1.14-2.40, adjusted by sex and age); the G allele showed a significant associated with NSCLC in dominant model (p=.003, OR=1.64, 95%CI: 1.18-2.28, adjusted by sex and age). Compared with haplotype H1 rs2227010-rs2734648-rs1799987-rs1799988-rs1800023-rs1800024: A-T-G-T-G-C, haplotype H5: A-G-G-T-G-C increased the risk of NSCLC by over 10-fold (p<.0001, OR=16.09, 95%CI: 5.37-48.20, adjusted by sex and age) and notably depressed the transcriptional activity of the CCR5 promoter in 293T, A549, H1299 and HeLa cells. In conclusion, CCR5 promoter polymorphisms are significantly associated with NSCLC by affecting the transcriptional activity of the CCR5 promoter.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Efficacy and Safety of PD-1/PD-L1 Inhibitors Combined with Radiotherapy in Patients with Brain Metastases Caused by Non-Small Cell Lung Cancer: A Multi-Center Retrospective Analysis

To investigate efficacy and safety of PD-1/PD-L1 inhibitors plus radiotherapy in patients that brain metastases (BMs) from non-small cell lung cancer (NSCLC). All 234 eligible patients were divided into PD-1/PD-L1 inhibitors plus intracranial radiotherapy (BM-RT) group and immunotherapy (non-BM-RT) group. 144 patients in BM-RT group were divided into patients received extracranial radiotherapy for NSCLC (extra-RT) group and had not (non-extra-RT) group. According to the Lung Immune Prognostic Index (LIPI), patients were stratified into good, intermediate, and poor groups. The toxicity was assessed with Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Kaplan-Meier method and Log-rank test were used to analyze intracranial progression-free survival (iPFS) and overall survival (OS). The median iPFS (11.6 months vs. 9.9 months, P = 0.001) and median OS (17.3 months vs. 14.6 months, P = 0.029) had a significant difference in BM-RT group and non-BM-RT group. Meanwhile, median iPFS (15.7 months vs. 10.5 months, P<0.001) and median OS (20.2 months vs. 15.1 months, P = 0.024) in extra-RT group were longer than non-extra-RT group. The median iPFS (12.9 months vs. 10.4 vs. 8.4 months, P = 0.001) and median OS (20.1 months vs. 16.7 months vs. 12.6 months, P = 0.025) were longer in good group than intermediate group and poor group in LIPI. Our data suggested there was a significant difference in iPFS and OS with or without radiotherapy in patients of BMs from NSCLC, and with safety profiles. LIPI helped predict prognosis of BMs in NSCLC.

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors

Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. ClinicalTrials.gov Identifier: NCT01463423.

Plasma levels of 12 different cytokines correlate to PD-1 inhibitor combined chemotherapy responses in advanced non-small-cell lung cancer patient

BackgroundTargeted anti-programmed death receptor 1 (PD-1) monoclonal antibodies, when combined with chemotherapy, have shown improved outcomes in non-small cell lung cancer (NSCLC). However, it is important to note that not all patients benefit from this treatment, and there is a pressing need for more reliable efficacy measures and potential predictors of outcome. Cytokines, which are important molecules in the immune system, have been considered as potential biomarkers in clinical settings, but their precise clinical use remains unclear. In this study, our objective was to assess whether the levels of cytokines in the patient's blood sample are associated with tumor response to anti-PD-1 monoclonal antibodies combined with chemotherapy as well as the survival of patients with advanced non-small cell lung cancer. Materials and MethodsA total of 12 plasma cytokines were measured in advanced NSCLC patients (n = 35) and healthy individuals (n = 26) using multi-microsphere flow immunofluorescence. The relationship between cytokine levels and clinical response was analyzed using nonparametric Wilcoxon matched-pair ranked tests. Progression-free survival (PFS) time was recorded for all patients through radiographic outcome assessment and telephone follow-up. Survival curves were generated using the Kaplan-Meier and log-rank tests, and the thresholds for cytokines were determined using receiver operating characteristic analysis (ROC). ResultsThe expression levels of interleukin IL-6, IL-1 β, IFN-γ, IL-12p70, and TNF-α were significantly lower in the control group than those in the NSCLC group (p = 0.001, p = 0.0028, p = 0.019, p = 0.0001, p = 0.0021). High IL-10 levels at baseline and after 4 cycles of treatment conferred a worse prognosis; in addition, high TNF-α levels in patients after two cycles of immunochemotherapy suggested drug resistance. High levels of IL-6 and IFN-γ in patients undergoing four cycles of immunochemotherapy were associated with worse PFS. ConclusionsOur study suggests that cytokines can serve as detection indicators for predicting efficacy in non-small cell lung cancer patients undergoing anti-PD-1 combined with chemotherapy treatment. Elevated levels of IL-10, TNF-α, IL-6, and IFN-γ in the plasma may indicate a higher likelihood of experiencing a worse clinical outcome.

Whole-tumor histogram analysis of multi-parametric MRI for differentiating brain metastases histological subtypes in lung cancers: relationship with the Ki-67 proliferation index.

This study aims to investigate the predictive value of preoperative whole-tumor histogram analysis of multi-parametric MRI for histological subtypes in patients with lung cancer brain metastases (BMs) and explore the correlation between histogram parameters and Ki-67 proliferation index. The preoperative MRI data of 95 lung cancer BM lesions obtained from 73 patients (42 men and 31 women) were retrospectively analyzed. Multi-parametric MRI histogram was used to distinguish small-cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC), and adenocarcinoma (AC) from squamous cell carcinoma (SCC), respectively. The T1-weighted contrast-enhanced (T1C) and apparent diffusion coefficient (ADC) histogram parameters of the volumes of interest (VOIs) in all BMs lesions were extracted using FireVoxel software. The following histogram parameters were obtained: maximum, minimum, mean, standard deviation (SD), variance, coefficient of variation (CV), skewness, kurtosis, entropy, and 1st-99th percentiles. Then investigated their relationship with the Ki-67 proliferation index. The skewness-T1C, kurtosis-T1C, minimum-ADC, mean-ADC, CV-ADC and 1st - 90th ADC percentiles were significantly different between the SCLC and NSCLC groups (all p < 0.05). When the 10th-ADC percentile was 668, the sensitivity, specificity, and accuracy (90.80%, 76.70% and 86.32%, respectively) for distinguishing SCLC from NSCLC reached their maximum values, with an AUC of 0.895 (0.824 - 0.966). Mean-T1C, CV-T1C, skewness-T1C, 1st - 50th T1C percentiles, maximum-ADC, SD-ADC, variance-ADC and 75th - 99th ADC percentiles were significantly different between the AC and SCC groups (all p < 0.05). When the CV-T1C percentiles was 3.13, the sensitivity, specificity and accuracy (75.00%, 75.60% and 75.38%, respectively) for distinguishing AC and SCC reached their maximum values, with an AUC of 0.829 (0.728-0.929). The 5th-ADC and 10th-ADC percentiles were strongly correlated with the Ki-67 proliferation index in BMs. Multi-parametric MRI histogram parameters can be used to identify the histological subtypes of lung cancer BMs and predict the Ki-67 proliferation index.