Effect of Osimertinib on the expression of serum mmp-7 and mmp-9 in patients with non-small cell lung cancer.

The purpose was to investigate the efficacy and safety of Osimertinib in the treatment of advanced non-small cell lung cancer and to analyze its effects on the expression of serum matrix metalloproteinase-7 (MMP-7) and matrix metallo-proteinase-9 (MMP-9). Eighty patients were equally divided into observation and control group. The observation group was given Osimertinib combined with conventional chemotherapy and the other was treated with conventional chemotherapy alone. The short-term efficacy, the levels of serum MMP-7, MMP-9 and adverse reactions were compared. The effectiveness and clinical benefit rate of the observation group were 62.50% and 92.50% respectively, significantly higher than the control group. There was no significant difference in MMP-7 and MMP-9 before treatment however there was a significant difference after treatment, and the serum MMP-7 & MMP-9 levels showed a trend of increasing with decreasing efficacy. After treatment, comparing with control group, serum MMP-7 and MMP-9 levels were significantly lower, the Karnofsky score was significantly higher, and the improvement effect of the quality of life was statistically significant. Besides, the incidence of leukopenia, thrombocytopenia, anemia and gastrointestinal symptoms were significantly lower. In the treatment of patients with advanced non-small cell lung cancer, Osimertinib significantly reduced the expression of serum MMP-7, MMP-9, improved the clinical benefit and quality of life of patients. The clinical efficacy was significant with a high safety.

Association Between BMI and Recurrence of Primary Spontaneous Pneumothorax.

BACKGROUND: Whether body mass index (BMI) is a significant risk factor for recurrence of primary spontaneous pneumothorax (PSP) remains controversial. The purpose of this study was to examine whether BMI and other factors are linked to risk of PSP recurrence. METHODS: A consecutive cohort of 273 patients was retrospectively evaluated. Patients were divided into those who experienced recurrence (n = 81) and those who did not (n = 192), as well as into those who had low BMI (n = 75) and those who had normal or elevated BMI (n = 198). The two pairs of groups were compared in terms of baseline data, and Cox proportional hazards modeling was used to identify predictors of PSP recurrence. RESULTS: Rates of recurrence among all 273 patients were 20.9% at 1 year, 23.8% at 2 years, and 28.7% at 5 years. Univariate analysis identified the following significant predictors of PSP recurrence: height, weight, BMI, size of pneumothorax, and treatment modality. Multivariate analyses identified several risk factors for PSP recurrence: low BMI, pneumothorax size ≥50%, and non-surgical treatment. Kaplan-Meier survival analysis indicated that patients with low BMI showed significantly lower recurrence-free survival than patients with normal or elevated BMI (P < 0.001). CONCLUSIONS: Low BMI, pneumothorax size ≥50%, and non-surgical treatment were risk factors for PSP recurrence in our cohort. Low BMI may be a clinically useful predictor of PSP recurrence.

Association between ERCC2 Lys751Gln polymorphism and lung cancer risk: a meta-analysis involving 23,370 subjects.

Recent studies report a correlation between excision repair cross-complementing group 2 (ERCC2) Lys751Gln polymorphism and an increased risk of lung cancer, but results are controversial and inconclusive. Thus, we conducted a comprehensive meta-analysis in order to assess the correlation between them. Our study uses an odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the strength of the association; we also performed Begg's funnel plot and the Egger's test to assess the publication bias of previous articles. Finally, our meta-analysis is comprised of 28 full studies, including 23,370 subjects (10,242 cases and 13,128 controls). Our overall research shows that ERCC2 Lys751Gln polymorphism carries an increased risk of developing lung cancer (C vs. A: OR = 1.160, 95% CI = 1.081-1.245, p = .000; CC vs. AA: OR = 1.252, 95% CI = 1.130-1.388, p = .000; CA vs. AA: OR = 1.152, 95% CI = 1.060-1.252, p = .001; CC+CA vs. AA: OR = 1.186, 95% CI = 1.089-1.292, p = .000; CC vs. CA+AA: OR = 1.196, 95% CI = 1.087-1.316, p = .000). In ethnic subgroup analyses, we find a significant risk among Caucasians (C vs. A: OR = 1.106, 95% CI = 1.048-1.166, p = .000; CC vs. AA: OR = 1.233, 95% CI = 1.103-1.378, p = .000; CC+CA vs. AA: OR = 1.113, 95% CI = 1.033-1.199, p = .005; CC vs. CA+AA: OR = 1.185, 95% CI = 1.069-1.313, p = .001) and among Asians under two genetic models (CA vs. AA: OR = 1.265, 95% CI = 1.034-1.549, p = .023; CC+CA vs. AA: OR = 1.252, 95% CI = 1.015-1.544, p = .036). These results were confirmed by similar findings, demonstrated by stratified analyses in study design and histological typing. This meta-analysis indicates that ERCC2 Lys751Gln polymorphism may lead to an increased susceptibility to lung cancer risk among Caucasians and Asians.

Enhanced recovery after surgery for percutaneous CT-guided microwave ablation of lung tumors: A single-center retrospective cohort study.

BACKGROUND: The feasibility and safety of enhanced recovery after surgery (ERAS) for percutaneous computed tomography (CT)-guided microwave ablation (MWA) for treating lung nodules remain unclear. METHODS AND MATERIALS: A total of 409 patients with lung tumors treated at the Department of Thoracic Surgery, First Affiliated Hospital of Guangxi Medical University from August 2020 to May 2023 were enrolled. Perioperative data, including baseline characteristics, operation time, postoperative pain score (visual analog scale [VAS]), hospitalization expenses, postoperative complications, total hospital stay, and patient satisfaction, were observed and recorded. RESULTS: No perioperative mortality occurred in either group and complete ablation was achieved in all patients. Patients in the ERAS group had significantly shorter hospital stays (P < 0.001), reduced operation times (P = 0.047), lower hospitalization expenses (P < 0.001), lower VAS scores (P < 0.001), and fewer complications (P = 0.047) compared with the traditional group. CONCLUSIONS: ERAS for percutaneous CT-guided MWA (ERAA) is safe, effective, and feasible for the treatment of lung nodules.

Intraventricular Thrombosis and Pulmonary Embolism Post-Nuss Procedure: A Rare Case of Chronic Bar Displacement in a 16-Year-Old Patient.

This novel report presents the first known case, to our knowledge, of a 16-year-old male patient who experienced intraventricular thrombosis and pulmonary embolism after a Nuss procedure for pectus excavatum, attributed to chronic bar displacement. Two years after the operation, the patient experienced post-exercise cough and hemoptysis, which led to his admission. Imaging revealed pulmonary embolism, thrombosis in the right ventricular outflow tract, and lung infiltrative lesions. We hypothesize that the chronic bar displacement led to its embedment in the right ventricle, resulting in thrombus formation, which subsequently contributed to partial pulmonary embolism. Surgery revealed the bars' intrusion into the right ventricle and lung. This case highlights the risk of severe complications from bar displacement in the Nuss procedure, which necessitates long-term follow-up evaluation, caution against strenuous activities after surgery, and use of thoracoscopic guidance during bar implantation and removal. It underscores the importance of vigilant evaluation for late-stage complications in patients with respiratory distress or thrombosis after a Nuss procedure.

Prediction of lymph node metastasis of lung squamous cell carcinoma by machine learning algorithm classifiers.

BACKGROUND: Lymph node metastasis (LNM) is an essential factor affecting the prognosis of patients with lung squamous cell carcinoma (LUSC), as well as a critical consideration for the choice of treatment strategy. Exploring effective methods for predicting LNM in LUSC may benefit clinical decision making. MATERIALS AND METHODS: We used data collected from the Surveillance, Epidemiology, and End Results (SEER) database to develop machine learning algorithm classifiers, including boosted trees (BTs), based on the primary clinical parameters of patients to predict LNM in LUSC. Training on a large-sample training cohort (n = 8,063) allowed for the construction of several concise classifiers for LNM prediction in LUSC, which were then validated using test and in-house cohorts (n = 2,017 and 57, respectively). RESULTS: The six classifiers established in this research enabled distinction between patients with and without LNM. Among these classifiers, the BT classifier was the top performer, with accuracy, F1 scores, precision, recall, sensitivity, and specificity values of 0.654, 0.621, 0.654, 0.592, 0.592, and 0.711, respectively. The precision recall (PR) and receiver operating characteristic (ROC) (with area under the curve = 0.714) curves also supported this result, which was validated by the in-house cohort. Notably, the tumor stage was a critical factor in determining LNM in patients with LUSC. CONCLUSIONS: The use of classifiers, especially the BT classifier, may serve as a useful tool for improving clinical precision and individualized treatment of patients with LUSC.

Landscape of somatic alterations in large-scale solid tumors from an Asian population.

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.

Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung carcinoma.

BACKGROUND: Squamous cell lung carcinoma (LUSC) was closely associated with smoking which was known to have a distant immunosuppression effect. In this study, we aimed to explore the relationship between immune cells and clinical outcomes of LUSC patients with smoking history. METHODS: The immune cell infiltration and RNA expression profiles of LUSC patients were collected from The Cancer Genome Atlas (TCGA). Then, the correlation between immune cell infiltration and clinical characteristics was explored. According to the level of immune cell infiltration, LUSC patients with smoking history were divided into high or low group to screen the differentially expressed lncRNAs and mRNAs. The prediction of target genes was performed by miRanda. Finally, the prognostic value of a certain signature was confirmed in an independent dataset. RESULTS: Higher abundance of tumor-infiltrating T follicular helper (Tfh) cells together with a lower abundance of resting memory CD4 T cells had been found in LUSC current reformed smokers for ≤15 years and current smoking patients. Moreover, Tfh cell infiltration was not only associated with better overall survival (OS) but also varied from different degrees of TNM stage. Low expression of lncRNA PWRN1 and its potential regulating genes DMRTB1, PIRT, APOBEC1, and ZPBP2 were associated with better OS. Combining PWRN1 and four regulating genes as a signature, patients with higher-level expression of the signature had shorter survival time in not only the TCGA but also in the GEO dataset. CONCLUSIONS: It was found that Tfh cells presented higher infiltration in LUSC current reformed smokers for ≤15 years and current smokers, while resting memory CD4 T cells had lower infiltration. The signature consisting of PWRN1 as well as its predicted targeted mRNAs was dysregulated in different levels of Tfh cell infiltration and might indicate patients' OS.

Clinical significance of Ki67 and circulating tumor cells with an epithelial-mesenchymal transition phenotype in non-small cell lung cancer.

Circulating tumor cells (CTCs) are a heterogeneous population of tumor cells with distinct clinical and biological properties. The aim of the present study was to evaluate the relationship between CTCs with the epithelial-mesenchymal transition phenotype (CTC EMT) and the proliferative marker Ki67, and their prognostic value in non-small cell lung cancer (NSCLC). CTCs were isolated from the peripheral blood of 84 NSCLC patients using the CanPatrolTM CTC enrichment method, and the expression of Ki67 in tumor tissues were detected by immunohistochemistry. Almost two-thirds (61/84) of the patients were positive for CTC EMT, and 55 (65.4%) patients had high in-situ expression of Ki67 (≥ 14%) in the tumor tissues. CTC EMT was not significantly associated with tumor size and differentiation, age, gender and histological type, but correlated with lymphatic metastasis, tumor stage and Ki67 overexpression. Furthermore, the CTC EMT+ NSCLC patients had a significantly lower recurrence-free survival (RFS) and overall survival (OS) compared to the negative patients. Similarly, Ki67 levels ≥ 14% were associated with a significantly lower RFS and OS. In conclusion, CTC EMT is significantly related to Ki67 expression, and is a risk factor of NSCLC.

Clinical Significance of Red Cell Distribution Width and Circulating Tumor Cells with an Epithelial-Mesenchymal Transition Phenotype in Lung Adenocarcinoma.

OBJECTIVE: To determine the prognostic value of red cell distribution width (RDW) and circulating tumor cells with epithelial-mesenchymal transition phenotype (M-CTC) in lung adenocarcinoma (LUAD). PATIENTS AND METHODS: Clinical and laboratory data of 60 patients with LUAD were collected. CTCs were isolated from their peripheral blood using the CanPatrolTM CTC enrichment method. The indicators of RDW and neutrophil lymphocyte ratio (NLR) were calculated based on the laboratory standards. RESULTS: A total of 60 LUAD patients were enrolled, of which 19 (31.7%) had high RDW (>0.14) and 32 (53.3%) were positive for M-CTCs. There was no significant correlation between RDW and the clinical characteristics. M-CTC was not significantly associated with tumor size and differentiation, age, gender, tumor stage, and histological type but correlated significantly with lymphatic metastasis (P = 0.044), high NLR (>2.26, P = 0.023), and high RDW (>0.14, P = 0.036). Furthermore, the M-CTC+ LUAD patients had a significantly poor recurrence-free survival (RFS; Log rank P =0.001, HR = 2.749, 95% CI = 1.489-5.078) and overall survival (OS; Log rank P =0.022, HR = 2.283, 95% CI = 1.128-4.622) compared to the M-CTC- patients. Similarly, high RDW also correlated with worse RFS (Log rank P = 0.008, HR = 2.331, 95% CI = 1.248-4.353) and OS (Log rank P = 0.004, HR = 0.004, 95% CI = 1.398-5.525). CONCLUSION: M-CTC is significantly related to RDW and NLR, and an independent prognostic factor in LUAD.

[Effects of tumor suppressor gene TCF21 on the proliferation, migration and apoptosis of A549 cells].

BACKGROUND AND OBJECTIVE: TCF21, a newly discovered gene, exhibits tumor suppressor function in a variety of tumors. This study aims to observe the effects of TCF21 on the proliferation, apoptosis and migration of A549 human lung adenocarcinoma epithelial cells. METHODS: TCF21 was overexpressed in A549 cells via lentiviral transfection. Fluorescence-based quantitative polymerase chain reaction and Western blot analysis were used to analyze the expression of the target gene. Transwell, proliferation assay, and flow cytometry were applied to detect the effect of TCF21 overexpression on the migration, proliferation, and apoptosis of A549 cells after transfection. RESULTS: The proliferation and migration of A549 cells were inhibited, and the apoptotic rate was increased by overexpressing TCF21. CONCLUSIONS: The tumor suppressor gene, TCF21, significantly inhibits the proliferation and migration, as well as facilitates early apoptosis of A549 cells.

Polymorphism of ERCC2 Asp312Asn with lung cancer risk: evidence from 20,101 subjects.

The association between excision repair cross complementing group 2 (ERCC2) Asp312Asn polymorphism and lung cancer has been reported by many articles recently, but the results were controversial and inconclusive. Therefore, a meta-analysis was conducted to assess the relationship between them. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 22 full studies with 20,101 subjects (8719 cases and 11,382 controls) were included in our research. The meta-analysis result showed that no significant association was found between ERCC2 Asp312Asn polymorphism and lung cancer in overall analysis (AA vs. GG, OR=1.023, 95% CI=0.824-1.270, p=0.838; AG vs. GG, OR=1.003, 95% CI=0.936-1.074, p=0.942; AA+AG vs. GG, OR=1.013, 95% CI=0.949-1.082, p=0.697; AA vs. AG+GG, OR=1.033, 95% CI=0.841-1.270, p=0.755). In subset analyses of stratified ethnicity, significantly increased risk was found among Asians (AA vs. GG, OR=3.212, 95% CI=1.518-6.795, p=0.002; AA vs. AG+GG, OR=3.174, 95% CI=1.500-6.712, p=0.003), whereas the association was not found among Caucasians under any genetic models. When analyses were conducted based on the study design, it indicated that the risk of lung cancer might be significantly increased in a hospital-based study (AA vs. GG, OR=1.323, 95% CI=1.096-1.596, p=0.004; AA+AG vs. GG, OR=1.109, 95% CI=1.000-1.229, p=0.050; AA vs. AG+GG, OR=1.285, 95% CI=1.076-1.535, p=0.006). In addition, a significantly increased risk for nonsmokers was detected under the dominant model (AA+AG vs. GG, OR=1.460, 95% CI=1.095-1.948, p=0.010). In conclusion, this meta-analysis suggested ERCC2 Asp312Asn polymorphism may increase the risk of lung cancer among Asians, whereas not among Caucasians.

[The Expression of hTERT mRNA and p16 Protein in Non-small Cell Lung Cancer.].

BACKGROUND: hTERT and p16 are involved in oncogenesis and development of tumor. The aim of this study is to investigate the expression of human telomerase reverse transcriptase (hTERT) and p16 in non-small cell lung cancer (NSCLC). METHODS: The quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemistry were applied to detect the hTERT and p16 in tissue of 21 cases of lung benign diseases and 117 of non-small cell lung cancer and adjacent tissues, respectively. RESULTS: hTERT mRNA levels from NSCLC in 117 patients and normal lung tissue in 21 normal controls were 2.937+/-0.836 and 2.042+/-0.378, respectively (t=-5.242, P<0.01). Expression of p16 protein was observed in 85.7% of normal tissues, while 47.9% of lung cancer tissues showed p16 protein expression (P=0.004). The expression of hTERT mRNA was significantly correlated with the histology (P<0.05); the expression of p16 protein was significantly correlated with the clinical stage, degree of differentiation and lymph node metastasis (P<0.05). The significant correlation between the expression of hTERT and p16 (P<0.05). CONCLUSIONS: The hTERT may be useful in clinical diagnosis of NSCLC. Expression of hTERT and p16 is related to the carcinogenesis and development of NSCLC.