RESUMO
SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.
Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.
Assuntos
Humanos , Canais de Cloreto/metabolismo , Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Prognóstico , RNA Mensageiro , Linfócitos , Biomarcadores Tumorais , Canais de Cloreto/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismoRESUMO
OBJECTIVES: The objective of the evaluate was to study and determine the usefulness of immunohistochemistry (IHC) staining in neoplastic lung lesions. MATERIALS AND METHODS: We evaluated seven IHC stains in fifty lung cancers that included adenocarcinoma (AC), squamous cell carcinoma (SCC), small cell carcinoma, and carcinoid tumors. RESULTS: P63 was expressed in all the cases of SCCs and thyroid transcription factor-1 (TTF-1) was expressed in all cases of ACs. CK 5/6 was expressed in 77.77% of SCCs and CK 7 was expressed in 92.59% of ACs. Synaptophysin and chromogranin-A were expressed in 100% of neuroendocrine (NE) carcinomas. CONCLUSION: P63 and TTF-1 are sensitive markers for SCCs and ACs. Synaptophysin and Chromogranin-A are sensitive markers for NE carcinomas.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma de Pulmão/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/metabolismo , Prognóstico , Carcinoma de Pequenas Células do Pulmão/metabolismoRESUMO
Due to therapeutic advances, the subclassification of non-small cell lung carcinomas (NSCLC) between the adenocarcinomas and squamous cell carcinomas subtypes is essential for the practice of personalized and targeted medicine. The clinical management for these two NSCLC subtypes is different due to their different molecular properties and histological origins. Immunohistochemistry (IHC) markers such is TTF-1 play a key role in the differentiation of lung adenocarcinomas and squamous cell carcinomas. However, immunohistochemistry is a complex process involving many critical steps and the reliability of results depends on the standardization of the assay as well as the appropriate interpretation. Different laboratories use different reagents and different IHC approaches for the detection of TTF-1 in lung cancer tumors. Here we describe an automated IHC protocol used in our laboratory for the detection of TTF-1 in formalin-fixed, paraffin-embedded (FFPE) tissue sections from lung tumors.
Assuntos
Adenocarcinoma de Pulmão , Automação Laboratorial , Carcinoma de Células Escamosas , Imuno-Histoquímica , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MasculinoRESUMO
BACKGROUND: The treatment of choice for advanced non-small cell lung cancer is selected according to the presence of specific alterations. Patients should undergo molecular testing for relevant modifications and the mutational status of EGFR and translocation of ALK and ROS1 are commonly tested to offer the best intervention. In addition, the tests costs should also be taken in consideration. Therefore, this work was performed in order to evaluate the cost-effectiveness of a unique exam using NGS (next generation sequencing) versus other routinely used tests which involve RT-PCR and FISH. METHODS: The target population was NSCLC, adenocarcinoma, and candidates to first-line therapy. Two strategies were undertaken, strategy 1 corresponded to sequential tests with EGFR RT-PCR, then FISH for ALK and ROS1. Strategy 2 differed from 1 in that ALK and ROS1 translocation testing were performed simultaneously by FISH. Strategy 3 considered single test next-generation sequencing, a platform that includes EGFR, ALK and ROS1 genes. A decision tree analysis was used to model genetic testing options. From the test results, a microsimulation model was nested to estimate survival outcomes and costs of therapeutic options. RESULTS: The use of NGS added 24% extra true cases as well as extra costs attributed to the molecular testing. The ICER comparing NGS with sequential tests was US$ 3479.11/correct case detected. The NGS improved a slight gain in life years and QALYs. CONCLUSION: Our results indicated that, although precise, the molecular diagnosis by NGS of patients with advanced stage NSCLC adenocarcinoma histology was not cost-effective in terms of quality-adjusted life years from the perspective of the Brazilian supplementary health system.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Quinase do Linfoma Anaplásico/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Adenocarcinoma de Pulmão/economia , Adenocarcinoma de Pulmão/genética , Brasil , Análise Custo-Benefício/economia , Testes Diagnósticos de Rotina/economia , Receptores ErbB/genética , Testes Genéticos/economia , Sequenciamento de Nucleotídeos em Larga Escala/economia , Humanos , Mutação/genéticaRESUMO
Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Inflamação/complicações , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/etiologia , Adulto , Idoso , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/etiologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/imunologia , Cinurenina/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/etiologia , Triptofano/sangueRESUMO
The lymphomas of mucosa-associated lymphoid tissue (MALT), are uncommon entities, of low grade of malignancy with very infrequent or no lymph node involvement. They represent about 80% of the primary pulmonary lymphomas. The synchronous appearance with lung adenocarcinoma is an extremely rare finding. We present the case of an ex-smoker 68-year-old man, in whom, in the follow-up of a pulmonary nodule, a second pulmonary nodule was found. The surgical biopsy confirmed the diagnosis of both neoplasms.
Los linfomas derivados del tejido linfoide asociado a las mucosas (MALT) son entidades poco frecuentes, de bajo grado de malignidad con escaso o nulo compromiso ganglionar y representan cerca del 80% de los linfomas primarios pulmonares. La aparición sincrónica con adenocarcinoma de pulmón es un hallazgo extremadamente infrecuente. Presentamos el caso de un hombre de 68 años, ex-tabaquista, en quien durante el seguimiento de un nódulo pulmonar se identificó un segundo nódulo y la biopsia quirúrgica confirmó el diagnóstico de ambas neoplasias.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Los linfomas derivados del tejido linfoide asociado a las mucosas (MALT) son entidades poco frecuentes, de bajo grado de malignidad con escaso o nulo compromiso ganglionar y representan cerca del 80% de los linfomas primarios pulmonares. La aparición sincrónica con adenocarcinoma de pulmón es un hallazgo extremadamente infrecuente. Presentamos el caso de un hombre de 68 años, ex-tabaquista, en quien durante el seguimiento de un nódulo pulmonar se identificó un segundo nódulo y la biopsia quirúrgica confirmó el diagnóstico de ambas neoplasias.
The lymphomas of mucosa-associated lymphoid tissue (MALT), are uncommon entities, of low grade of malignancy with very infrequent or no lymph node involvement. They represent about 80% of the primary pulmonary lymphomas. The synchronous appearance with lung adenocarcinoma is an extremely rare finding. We present the case of an ex-smoker 68-year-old man, in whom, in the follow-up of a pulmonary nodule, a second pulmonary nodule was found. The surgical biopsy confirmed the diagnosis of both neoplasms.