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2.
Front Immunol ; 15: 1382231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646528

RESUMO

Background: Integrin subunit alpha L (ITGAL) encodes an integrin component of LFA-1 and is a membrane receptor molecule widely expressed on leukocytes. It plays a key role in the interaction between white blood cells and other cells. There was a significant correlation between the expression of ITGAL and the tumor microenvironment in a number of cancers. However, experimental studies targeting ITGAL and immune cell infiltration in non-small-cell lung cancer (NSCLC) and the response to immune checkpoint inhibitor therapy are lacking. Methods: Data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to explore the relationship between ITGAL expression and prognosis, as well as the immune cell infiltration in patients with NSCLC. In addition, immunohistochemical staining for ITGAL and multiplex immunofluorescence (mIF) staining for ITGAL, CD20, CD68, CD4, and CD8 from tissue microarrays containing 118 tumor tissues and paired paracancerous tissues from patients with NSCLC were performed. The correlation between ITGAL expression and clinical factors, as well as the immunophenotypes of tumor-infiltrating immune cells, were also analyzed. Results: In NSCLC tumor tissues, ITGAL was downregulated compared with matched paracancerous tissues, and low ITGAL expression was associated with a poor prognosis of NSCLC patients. Subsequently, immunohistochemistry results for tissue microarray showed that ITGAL expression was mainly elevated in tumor stroma and areas with highly infiltrated immune cells. ITGAL expression was higher in paracancerous tissues than tumor tissues. Furthermore, mIF results indicated that the patients with ITGAL-high expression tend had significantly higher CD8+ T cells, CD68+ macrophages, CD4+ T cells, and CD20+ B cells infiltration in their tumor tissues. Immunophenotypes were classified into three categories, that is deserted, excluded, and inflamed types, according to each kind of immune cell distribution in or around the cancer cell nest. MIF results showed that ITGAL expression level was correlated with the immunophenotypes. Furthermore, ITGAL expression was associated with the prognosis of NSCLC in patients with immune checkpoint inhibitor therapy and the patients with high ITGAL expression tends have better outcomes. Conclusions: ITGAL may be used as a biomarker for assessing the immune microenvironment in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Microambiente Tumoral/imunologia , Integrina alfa1/metabolismo
3.
Curr Oncol ; 30(1): 315-325, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-36661674

RESUMO

(1) Background: It has yet to be determined whether preoperative flexible bronchoscopy (FB) should be routinely performed in patients with peripheral lung cancer. The aim of this study was to construct a model to predict the probability of positive FB findings, which would help assess the necessity of preoperative FB. (2) Methods: A total of 380 consecutive patients with peripheral lung cancer who underwent preoperative FB were recruited for this study. A prediction model was developed through univariate and multivariate logistic regression, with predictors including gender, age, body mass index (BMI), smoking, history of chronic lung diseases, respiratory symptoms, lesion size, lesion type, lesion location in the bronchi, and lesion location in the lobe. The predictive performance of the model was evaluated by validation using 1000 iterations of bootstrap resampling. Model discrimination was assessed using the area under the receiver operating characteristics curve (AUC), and calibration was assessed using the Brier score and calibration plots. (3) Results: The model suggested that male patients with respiratory symptoms, decreased BMI, solid lesions, and lesions located in lower-order bronchi were more likely to have positive FB findings. The AUC and Brier score of the model for internal validation were 0.784 and 0.162, respectively. The calibration curve for the probability of positive FB findings showed convincing concordance between the predicted and actual results. (4) Conclusions: Our prediction model estimated the pretest probability of positive FB findings in patients with peripheral lung cancers. Males and patients with lower BMI, the presence of respiratory symptoms, larger lesions, solid lesions, and lesions located in lower-order bronchi were associated with increased positive FB findings. The use of our model can be of assistance when making clinical decisions about preoperative FB.


Assuntos
Broncoscopia , Neoplasias Pulmonares , Humanos , Masculino , Broncoscopia/métodos , Neoplasias Pulmonares/patologia , Modelos Logísticos
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