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1.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206291

RESUMO

Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa's cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete (MUC2) and incomplete (MUC2, MUC5AC, and MUC6) intestinal metaplasia, gastric dysplasia/intra-epithelial neoplasia, and early gastric cancer. In particular, considering preinvasive neoplasia and early gastric cancer, some studies have demonstrated a correlation between molecular alterations and prognosis, for example, mucins phenotype in gastric dysplasia, and GATA6, TP53 mutation/LOH and MUC6 in early gastric cancer. Moreover, this review considers novelties from the literature regarding the (immuno)histochemical characterization of diffuse-type/signet ring cell gastric cancer, with particular attention to clinical outcomes of patients. The aim of this review is the evaluation of the state of the art regarding suitable biomarkers used in the pre-surgical phase, which can distinguish patients with different prognoses and help decide the best therapeutic strategy.


Assuntos
Neoplasias Gástricas/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Fator de Transcrição GATA6/análise , Fator de Transcrição GATA6/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Intestinos , Metaplasia/diagnóstico , Metaplasia/genética , Metaplasia/metabolismo , Mucina-5AC/análise , Mucina-5AC/genética , Mucina-2/análise , Mucina-2/genética , Mucina-6/análise , Mucina-6/genética , Mutação , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genética
2.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206297

RESUMO

Increased cell proliferation is a hallmark of acute lymphoblastic leukemia (ALL), and genetic alterations driving clonal proliferation have been identified as prognostic factors. To evaluate replicative history and its potential prognostic value, we determined telomere length (TL) in lymphoblasts, B-, and T-lymphocytes, and measured telomerase activity (TA) in leukocytes of patients with ALL. In addition, we evaluated the potential to suppress the in vitro growth of B-ALL cells by the telomerase inhibitor imetelstat. We found a significantly lower TL in lymphoblasts (4.3 kb in pediatric and 2.3 kb in adult patients with ALL) compared to B- and T-lymphocytes (8.0 kb and 8.2 kb in pediatric, and 6.4 kb and 5.5 kb in adult patients with ALL). TA in leukocytes was 3.2 TA/C for pediatric and 0.7 TA/C for adult patients. Notably, patients with high-risk pediatric ALL had a significantly higher TA of 6.6 TA/C compared to non-high-risk patients with 2.2 TA/C. The inhibition of telomerase with imetelstat ex vivo led to significant dose-dependent apoptosis of B-ALL cells. These results suggest that TL reflects clonal expansion and indicate that elevated TA correlates with high-risk pediatric ALL. In addition, telomerase inhibition induces apoptosis of B-ALL cells cultured in vitro. TL and TA might complement established markers for the identification of patients with high-risk ALL. Moreover, TA seems to be an effective therapeutic target; hence, telomerase inhibitors, such as imetelstat, may augment standard ALL treatment.


Assuntos
Oligonucleotídeos/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Telomerase/antagonistas & inibidores , Telômero/metabolismo , Adolescente , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Oligonucleotídeos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Prognóstico , Telomerase/metabolismo , Homeostase do Telômero
3.
Medicine (Baltimore) ; 100(25): e26378, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160413

RESUMO

RATIONALE: Pyloric gland adenoma (PGA) is often associated with pyloric gland metaplasia. It has high malignant potential but a low clinical diagnosis rate. Therefore, we reported a case of PGA and reviewed the literature to summarize the clinicopathological features of pyloric adenoma. PATIENT CONCERNS: A 62-year-old female underwent gastroscopy due to intermittent acid regurgitation and heartburn, which revealed a 4×6 mm flat, elevated lesion in the greater curvature of the upper gastric body, with depression in the central region and blood scab attachment. DIAGNOSIS AND INTERVENTION: Biopsy revealed gastric adenoma with low-grade intraepithelial neoplasia. The patient was treated with ESD, and pathology showed gastric pyloric gland adenoma with low-grade dysplasia. The cells were positive for MUC6 and MUC5AC immunohistochemically. OUTCOMES: The patient received proton pump inhibitors and gastric mucosal protective agents for one month after ESD. She occasionally presented acid regurgitation and heartburn, with no abdominal pain, abdominal distension, melena, or hematochezia. Follow-up gastroscopy will be reexamined 1 year later. LESSONS: PGA has nonspecific performance under endoscopy, and its diagnosis mainly depends on pathology. Clinicians need to increase their ability to recognize such lesions and treat them in time to improve the prognosis.


Assuntos
Adenoma/diagnóstico , Carcinoma in Situ/diagnóstico , Mucosa Gástrica/patologia , Antro Pilórico/patologia , Neoplasias Gástricas/diagnóstico , Adenoma/patologia , Adenoma/cirurgia , Biomarcadores Tumorais/análise , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Ressecção Endoscópica de Mucosa , Feminino , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/cirurgia , Gastroscopia , Humanos , Pessoa de Meia-Idade , Antro Pilórico/diagnóstico por imagem , Antro Pilórico/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
4.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063506

RESUMO

The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical position. Translational sciences deeply investigated the field, accelerating the pace toward clinical transition, due to its strong association with outcomes. While the perturbation of gut homeostasis occurring in inflammatory bowel diseases can fuel carcinogenesis, micronutrients like vitamin D and calcium can act as brakes, and we discuss underlying molecular mechanisms. Among the components of gut microbiota, Fusobacterium nucleatum is over-represented in CRC, and may worsen patient outcome. However, any translational knowledge tracing the multifaceted evolution of CRC should be interpreted according to the prognostic and predictive frame of the TNM-staging system in a perspective of clinical actionability. Eventually, we examine challenges and promises of pharmacological interventions aimed to restrain disease progression at different disease stages.


Assuntos
Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Microambiente Tumoral/imunologia , Anticarcinógenos/farmacologia , Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos , Fusobacterium nucleatum/metabolismo , Microbioma Gastrointestinal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Micronutrientes/farmacologia , Microambiente Tumoral/genética , Microambiente Tumoral/fisiologia
5.
Br J Radiol ; 94(1123): 20201125, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34142870

RESUMO

OBJECTIVE: To investigate whether BIRADS MRI characteristics before or during neoadjuvant endocrine therapy (NET) are associated with the preoperative endocrine prognostic index (PEPI) in ER+/HER2- breast cancer patients. METHODS: This retrospective observational cohort study included 35 ER+/HER2- patients with 38 tumors (3 bilateral cases) treated with NET. The pre- and midtreatment (after 3 months) MRIs were evaluated by two breast radiologists for BIRADS imaging characteristics, shrinkage pattern, and radiologic response. PEPI was used as end point. PEPI is based on the post-treatment surgical specimen's pT- and pN-stage, Ki67, and ER-status. Tumors were assigned PEPI-1 (good prognosis) or PEPI-2/3 (poor prognosis). We investigated whether pre- and midtreatment BIRADS characteristics were associated with PEPI. RESULTS: Median patient age was 65 years (interquartile interval [IQI]: 53, 70). 17 tumors (44.7%) were associated with good prognosis (PEPI-1), and 21 tumors (55.3%) with poor prognosis (PEPI-2/3). A larger reduction in tumor size after 3 months of NET was significantly associated with PEPI; 10 mm (IQI: 5, 13.5) in PEPI-1 tumors vs 4.5 mm (IQI: 3, 7; p = .045) in PEPI-2/3 tumors. Other BIRADS characteristics, shrinkage pattern or radiologic response were not associated with PEPI. CONCLUSION: Only a larger reduction in tumor size on MRI after 3 months of NET was associated with PEPI-1 (good prognosis) in ER+/HER2- breast cancer patients. ADVANCES IN KNOWLEDGE: MRI characteristics previously reported to be associated with prognosis during neoadjuvant chemotherapy are not necessarily associated with prognosis during NET in ER+/HER2- breast cancer patients.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Receptores de Estrogênio/análise , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Meios de Contraste , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/análise , Estudos Retrospectivos , Tamoxifeno/administração & dosagem
6.
Sensors (Basel) ; 21(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065481

RESUMO

Human epididymis protein 4 (HE4) is an ovarian cancer marker. Various cut-off values of the marker in blood are recommended, depending on the method used for its determination. An alternative biosensor for HE4 determination in blood plasma has been developed. It consists of rabbit polyclonal antibody against HE4, covalently attached to a gold chip via cysteamine linker. The biosensor is used with the non-fluidic array SPRi technique. The linear range of the analytical signal response was found to be 2-120 pM, and the biosensor can be used for the determination of the HE4 marker in the plasma of both healthy subjects and ovarian cancer patients after suitable dilution with a PBS buffer. Precision (6-10%) and recovery (101.8-103.5%) were found to be acceptable, and the LOD was equal to 2 pM. The biosensor was validated by the parallel determination of a series of plasma samples from ovarian cancer patients using the Elecsys HE4 test and the developed biosensor, with a good agreement of the results (a Pearson coefficient of 0.989). An example of the diagnostic application of the developed biosensor is given-the influence of ovarian tumor resection on the level of HE4 in blood serum.


Assuntos
Técnicas Biossensoriais , Neoplasias Ovarianas , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Biomarcadores Tumorais/análise , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Plasma
7.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068143

RESUMO

Immune checkpoint inhibitor (ICI) therapies have shown great promise in cancer treatment. However, the intra-heterogeneity is a major barrier to reasonably classifying the potential benefited patients. Comprehensive heterogeneity analysis is needed to solve these clinical issues. In this study, the samples from pan-cancer and independent breast cancer datasets were divided into four tumor immune microenvironment (TIME) subtypes based on tumor programmed death ligand 1 (PD-L1) expression level and tumor-infiltrating lymphocyte (TIL) state. As the combination of the TIL Z score and PD-L1 expression showed superior prediction of response to ICI in multiple data sets compared to other methods, we used the TIL Z score and PD-L1 to classify samples. Therefore, samples were divided by combined TIL Z score and PD-L1 to identify four TIME subtypes, including type I (3.24%), type II (43.24%), type III (6.76%), and type IV (46.76%). Type I was associated with favorable prognosis with more T and DC cells, while type III had the poorest condition and composed a higher level of activated mast cells. Furthermore, TIME subtypes exhibited a distinct genetic and transcriptional feature: type III was observed to have the highest mutation rate (77.92%), while co-mutations patterns were characteristic in type I, and the PD-L1 positive subgroup showed higher carbohydrates, lipids, and xenobiotics metabolism compared to others. Overall, we developed a robust method to classify TIME and analyze the divergence of prognosis, immune cell composition, genomics, and transcriptomics patterns among TIME subtypes, which potentially provides insight for classification of TIME and a referrable theoretical basis for the screening benefited groups in the ICI immunotherapy.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Feminino , Seguimentos , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico , Taxa de Sobrevida
8.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069262

RESUMO

Aberrant glycosylation has long been known to be associated with cancer, since it is involved in key mechanisms such as tumour onset, development and progression. This review will focus on protein glycosylation studies in cells, tissue, urine and serum in the context of prostate cancer. A dedicated section will cover the glycoforms of prostate specific antigen, the molecule that, despite some important limitations, is routinely tested for helping prostate cancer diagnosis. Our aim is to provide readers with an overview of mass spectrometry-based glycoproteomics of prostate cancer. From this perspective, the first part of this review will illustrate the main strategies for glycopeptide enrichment and mass spectrometric analysis. The molecular information obtained by glycoproteomic analysis performed by mass spectrometry has led to new insights into the mechanism linking aberrant glycosylation to cancer cell proliferation, migration and immunoescape.


Assuntos
Biomarcadores Tumorais/análise , Espectrometria de Massas/métodos , Neoplasias da Próstata/metabolismo , Proteômica/métodos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/urina , Glicosilação , Humanos , Masculino , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina
9.
Science ; 372(6547)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112666

RESUMO

Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this "AstroPath" whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti-programmed cell death-1 (PD-1)-based therapy, including CD163+PD-L1- myeloid cells and CD8+FoxP3+PD-1low/mid T cells. These features were combined to stratify long-term survival after anti-PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/análise , Imunofluorescência , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígeno B7-H1/análise , Antígenos CD8/análise , Feminino , Fatores de Transcrição Forkhead/análise , Humanos , Proteínas de Checkpoint Imunológico/análise , Macrófagos/química , Masculino , Melanoma/química , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/análise , Intervalo Livre de Progressão , Receptores de Superfície Celular/análise , Fatores de Transcrição SOXE/análise , Análise de Célula Única , Subpopulações de Linfócitos T/química , Subpopulações de Linfócitos T/imunologia , Resultado do Tratamento , Microambiente Tumoral
10.
Nat Commun ; 12(1): 3515, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112774

RESUMO

MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 µl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.


Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Detecção Precoce de Câncer/métodos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias da Próstata/diagnóstico , Imagem Individual de Molécula/métodos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , MicroRNA Circulante/análise , MicroRNA Circulante/sangue , Detecção Precoce de Câncer/instrumentação , Fluorescência , Perfilação da Expressão Gênica , Humanos , Biópsia Líquida , Masculino , MicroRNAs/análise , MicroRNAs/sangue , MicroRNAs/genética , Nanoporos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
11.
J Clin Pathol ; 74(7): 429-434, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34117103

RESUMO

Clinical workflows in oncology depend on predictive and prognostic biomarkers. However, the growing number of complex biomarkers contributes to costly and delayed decision-making in routine oncology care and treatment. As cancer is expected to rank as the leading cause of death and the single most important barrier to increasing life expectancy in the 21st century, there is a major emphasis on precision medicine, particularly individualisation of treatment through better prediction of patient outcome. Over the past few years, both surgical and pathology specialties have suffered cutbacks and a low uptake of pathology specialists means a solution is required to enable high-throughput screening and personalised treatment in this area to alleviate bottlenecks. Digital imaging in pathology has undergone an exponential period of growth. Deep-learning (DL) platforms for hematoxylin and eosin (H&E) image analysis, with preliminary artificial intelligence (AI)-based grading capabilities of specimens, can evaluate image characteristics which may not be visually apparent to a pathologist and offer new possibilities for better modelling of disease appearance and possibly improve the prediction of disease stage and patient outcome. Although digital pathology and AI are still emerging areas, they are the critical components for advancing personalised medicine. Integration of transcriptomic analysis, clinical information and AI-based image analysis is yet an uncultivated field by which healthcare professionals can make improved treatment decisions in cancer. This short review describes the potential application of integrative AI in offering better detection, quantification, classification, prognosis and prediction of breast and prostate cancer and also highlights the utilisation of machine learning systems in biomarker evaluation.


Assuntos
Inteligência Artificial , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico , Inteligência Artificial/tendências , Feminino , Humanos , Masculino , Oncologia/métodos , Oncologia/tendências , Patologia Clínica/métodos , Patologia Clínica/tendências , Medicina de Precisão/métodos , Medicina de Precisão/tendências
12.
Medicine (Baltimore) ; 100(18): e25545, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950928

RESUMO

BACKGROUND: Breast cancer is a common malignant tumor in women. In recent years, its incidence is increasing year by year, and its morbidity and mortality rank the first place among female malignant tumors. Some key enzymes and intermediates in glycolysis are closely related to tumor development. Pyruvate kinase M2 (PKM2) is an important rate-limiting enzyme in glycolysis pathway. Meanwhile, it is highly expressed in proliferative cells, especially in tumor cells, and plays an important role in the formation of Warburg effect and tumorigenesis. Previous studies have explored the effects of PKM2 expression on the prognosis and clinical significance of breast cancer patients, while the results are contradictory and uncertain. This study uses controversial data for meta-analysis to accurately evaluate the problem. We collected relevant Oncomine and The Cancer Genome Atlas (TCGA) data to further verify the results. Through bioinformatics analysis, the mechanism and related pathways of PKM2 in breast cancer are explored. METHODS: We searched Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases from inception to March 2021. The language restrictions are Chinese and English. The published literatures on PKM2 expression and prognosis or clinicopathological characteristics of breast cancer patients were statistically analyzed. Combined hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (95% CIs) were used to evaluate the effects of PKM2 on the prognosis and clinicopathological features of breast cancer. Stata 14.0 software was applied for meta-analysis. Oncomine and TCGA databases were used to meta-analyze the differences of PKM2 mRNA expression between breast cancer and normal breast tissues. The expression of PKM2 protein was verified by Human Protein Atlas (HPA) database. The relationship between the gene and the survival of breast cancer patients was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). The relationship between PKM2 gene and clinicopathological characteristics was analyzed by using LinkedOmics, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis was performed by using Metascape. Protein-protein interaction (PPI) network was constructed by String website. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study provides high-quality medical evidence for the correlation between the expression of PKM2 and the prognosis and clinicopathological features of breast cancer. Through bioinformatics analysis, this study further deepens the understanding of the mechanism and related pathways of PKM2 in breast cancer. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W52HB.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Mama/patologia , Carcinogênese/patologia , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Proteínas de Transporte/análise , Biologia Computacional , Intervalo Livre de Doença , Feminino , Humanos , Proteínas de Membrana/análise , Metanálise como Assunto , Prognóstico , Medição de Risco/métodos , Hormônios Tireóideos/análise , Efeito Warburg em Oncologia
13.
Bull Cancer ; 108(7-8): 771-778, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34023063

RESUMO

Hairy cell leukemia is a rare form of leukemia: three hundred new cases are diagnosed each year in France. The diagnosis is based on: (1) morphological examination of the blood and bone marrow smear, (2) analysis by flow cytometry of hairy cells, which express three or the four following markers: CD11c, CD25, CD103 and CD123, (3) identification of the BRAFV600E mutation, a true molecular marker of the disease. The management of treatment has evolved considerably in recent years. As of today, the purine analogues remain the standard treatment in the first line. Relapses are however observed in about 40% of cases. In the event of a first relapse, the preferred option is treatment with immunochemotherapy i.e. a combination of cladribine plus rituximab. Subsequent relapses are treated with moxetumomab pasudotox or BRAF inhibitors which provide indisputable benefits if third-line treatment is required. We will discuss in patients with relapsed/refractory hairy cell leukemia the needs for personalized medicine and the advantages and disadvantages of each treatment modality. The good prognosis for LT requires treatments that are not immunosuppressive, non-myelotoxic, and do not increase the risk of secondary cancers.


Assuntos
Leucemia de Células Pilosas/terapia , Doenças Raras/terapia , Antígenos de Neoplasias/análise , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Toxinas Bacterianas/uso terapêutico , Biomarcadores Tumorais/análise , Cladribina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Exotoxinas/uso terapêutico , Humanos , Imunoterapia/métodos , Leucemia de Células Pilosas/diagnóstico , Mansonelose , Mutação , Segunda Neoplasia Primária/prevenção & controle , Pentostatina/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Doenças Raras/diagnóstico , Recidiva , Rituximab/uso terapêutico
14.
J Cancer Res Clin Oncol ; 147(8): 2301-2307, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34003366

RESUMO

PURPOSE: Monitoring mutation status in circulating free DNA (cfDNA) during target therapy could hold significant clinical importance in non-small cell lung cancer (NSCLC). Our aim is to establish if EGFR mutational status change on cfDNA has predictive value that can impact clinical management of NSCLC patients care. METHODS: This study included 30 patients with EGFR-mutated NSCLC. Blood samples were collected at diagnosis (T0) and in 19 patients during therapy (T1). RESULTS: Concordance between T0 and T1 EGFR mutation status for patients evaluable for both samples (n = 19) was 79%, with a sensitivity of 100% (95% CI: 55.5-100.0) and specificity of 60.0% (95% CI: 26.2-86.8). For the patients in oncological therapy with targeted drug and with T1 sample available (n = 18), survival outcomes were evaluated. For both mutation-negative T0 and T1 patients, 12-month progression-free survival (PFS) was 66.7% (95% CI: 27.2-100.0) and 12-month overall survival (OS) was 100% (95% CI: 1.00-1.00); for patients mutated both at T0 and T1, PFS was 22.2% (95% CI: 6.5-75.4%) and OS was 55.6% (95% CI: 20.4-96.1%). CONCLUSION: EGFR mutation status can be assessed using cfDNA for routine purposes and longitudinal assessment of plasma mutation is an easy approach to monitor the therapeutic response or resistance onset.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/genética , Análise Mutacional de DNA/métodos , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Receptores ErbB/análise , Receptores ErbB/genética , Feminino , Humanos , Itália/epidemiologia , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos
15.
Medicine (Baltimore) ; 100(21): e25861, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032698

RESUMO

RATIONALE: Gastric adenocarcinoma of fundic gland (chief cell predominant type) (GA-FG-CCP) is a new, rare variant of gastric adenocarcinoma, which is characterized by mild nuclear atypia and specific immunohistochemical markers. PATIENT CONCERNS: An 84-year-old Chinese man was referred to our hospital for endoscopic resection of a gastric lesion. INTERVENTIONS: We performed endoscopic submucosal dissection, and successfully removed the lesion. DIAGNOSIS: Esophago gastroduodenoscopy showed a slightly elevated lesion with a diameter of 22 mm in the posterior wall of cardia. Magnifying endoscopy with narrow band imaging revealed an abnormal microsurface and microvessels on the tumor surface. Endoscopic ultrasonography revealed a hypoechoic mass located in the first layer. The pathological diagnosis of the biopsy specimens indicated that the tumor was high grade intraepithelial neoplasia. The pathological diagnosis differed between the superficial and deeper part of the lesion. The superficial part was composed of a tubular structure with prominent atypia and was diagnosed as well differentiated intestinal adenocarcinoma. The deeper part was composed of a well-differentiated tubular adenocarcinoma mimicking the fundic gland cells, mainly the chief cells. The tumor cells showed mild nuclear atypia and was positive for pepsinogen-I (PG-I) and mucin-6 (MUC6). This deeper part was diagnosed as GA-FG-CCP. OUTCOMES: The tumor was successfully removed. This patient had no discomfort during the follow-up period (10 months). LESSONS: We present a rare case of GA-FG-CCP coexisted with well-differentiated tubular adenocarcinoma. GA-FG-CCP exists in the deep mucosal layer and the muscularis mucosa, which could not be found under endoscopy, but could be discerned in pathology with mild nuclear atypia and special biomarkers.


Assuntos
Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma/diagnóstico , Fundo Gástrico/patologia , Neoplasias Complexas Mistas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/cirurgia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Celulas Principais Gástricas/patologia , Endoscopia do Sistema Digestório , Endossonografia , Gastrectomia , Fundo Gástrico/citologia , Fundo Gástrico/diagnóstico por imagem , Fundo Gástrico/cirurgia , Humanos , Mucosa Intestinal/patologia , Masculino , Mucina-6/análise , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/cirurgia , Pepsinogênio A/análise , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
16.
Medicine (Baltimore) ; 100(21): e25993, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032716

RESUMO

ABSTRACT: Guanine nucleotide-binding protein-like-3-like (GNL3L) is required for processing ribosomal pre-rRNA and cell proliferation and is upregulated in many types of cancer. This study is aimed to investigate the clinical significance of GNL3L in esophageal cancer. The mRNA and protein expression levels of GNL3L were determined by using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. GNL3L was localized in both cytoplasm and nucleus. The expression levels of GNL3L in esophageal cancer tissues were significantly higher than those in adjacent nonmalignant tissues. High GNL3L expression was associated with pathologic type and poor differentiation. Patients with high GNL3L expression had shorter overall survival (OS) than those with low GNL3L expression. Multivariate Cox regression analysis revealed that GNL3L expression was an independently predictive factor for the OS of patient with esophageal cancer. The Gene Expression Profiling Interactive Analysis (GEPIA) databases also showed that GNL3L was upregulated in esophageal cancer, which was closely associated with an unfavorable prognosis of patients with esophageal cancer. Taken together, our findings suggest that GNL3L is upregulated in esophageal cancer, which is linked to the progression of the disease. As a result, GNL3L could be used as a biomarker for esophageal cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Proteínas de Ligação ao GTP/metabolismo , Proteínas Nucleares/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Núcleo Celular/patologia , Proliferação de Células , Quimioterapia Adjuvante/métodos , Citoplasma/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia , Esôfago/citologia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Proteínas de Ligação ao GTP/análise , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Prognóstico , Regulação para Cima
17.
Medicine (Baltimore) ; 100(21): e26068, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032736

RESUMO

ABSTRACT: Some patients with advanced colon adenocarcinoma (COAD) are not sensitive to radiotherapy and chemotherapy, and as such, immunotherapy has become the most popular option for these patients. However, different patients respond differently to immunotherapy. Tumor mutational burden (TMB) has been used as a predictor of the response of advanced COAD patients to immunotherapy. A high TMB typically indicates that the patient's immune system will respond well to immunotherapy. In addition, while microRNAs (miRNA) have been shown to play an important role in treatment responses associated with the immune system, the relationship between miRNA expression levels and TMB has not been clarified in COAD.We downloaded miRNA data and mutational files of COAD from the Cancer Genome Atlas database. Differentially expressed miRNAs were screened in the training group, and miRNAs used to construct the model were further identified using the LASSO logistic regression method. After building the miRNA-based model, we explored the correlation between the model and TMB. The model was verified by a receiver operating characteristic curve, and the correlation between it and 3 widely used immune checkpoints (programmed death receptor-1, programmed death-ligand 1, and cytotoxic T-lymphocyte associated protein-4) was explored. Functional enrichment analysis of the selected miRNAs was performed, and these respective miRNA target genes were predicted using online tools.Our results showed that a total of 32 differentially expressed miRNAs were used in the construction of the model. The accuracies of the models of the 2 datasets (training and test sets) were 0.987 and 0.934, respectively. Correlation analysis showed that the correlation of the model with programmed death-ligand 1 and cytotoxic T-lymphocyte associated protein-4, as well as TMB, was high, but there was no correlation with programmed death receptor-1. The results of functional enrichment analysis indicated that these 32 miRNAs were involved in many immune-related biological processes and tumor-related pathways.Therefore, this study demonstrated that differentially expressed miRNAs can be used to predict the TMB level, which can help identify advanced COAD patients who will respond well to immunotherapy. The miRNA-based model may be used as a tool to predict the TMB level in patients with advanced COAD.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/genética , MicroRNAs/metabolismo , Modelos Genéticos , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Análise Mutacional de DNA , Conjuntos de Dados como Assunto , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Logísticos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Curva ROC , Tolerância a Radiação/genética
18.
Medicine (Baltimore) ; 100(20): e25932, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011067

RESUMO

ABSTRACT: Platelet-derived growth factor A (PDGFA), the most known member of PDGF family, plays a crucial role in occurrence and progression of different tumors. However, PDGFA expression and its clinical significance in esophageal squamous cell carcinoma (ESCC) are not clear. The present study aimed to assess the expression and prognostic value of PDGFA in ESCC.The Gene Expression Omnibus databases (GSE53625, GSE23400, and GSE67269) and fresh clinical samples were employed for detecting PDGFA messenger RNA expression in ESCC. The associations of PDGFA expression with clinicopathological characteristics were evaluated by chi-square test. Kaplan-Meier analysis and Cox proportional hazard regression model were performed to determine the prognostic value of PDGFA in ESCC patients. PDGFA-related signaling pathways were defined by gene set enrichment analysis based on Gene Expression Omnibus databases.The PDGFA messenger RNA expression was upregulated in ESCC tissues compared with paired adjacent noncancerous tissues (P < .05) and was positively correlated with T stage (P < .05). Kaplan-Meier survival analysis suggested that ESCC patients with high PDGFA expression were associated with poorer overall survival compared to those with low PDGFA expression (P < .05), especially in advanced T stage (P < .05). Cox analyses showed that high expression of PDGFA was an independent predictor for poor prognosis in ESCC patients. Gene set enrichment analysis identified 3 signaling pathways (extracellular matrix receptor interaction, focal adhesion, and glycosaminoglycan biosynthesis chondroitin sulfate) that were enriched in PDGFA high expression phenotype (all P < .01).PDGFA may serve as an oncogene in ESCC and represent an independent molecular biomarker for prognosis of ESCC patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Conjuntos de Dados como Assunto , Mucosa Esofágica/patologia , Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Fator de Crescimento Derivado de Plaquetas , Prognóstico , Regulação para Cima
19.
Medicine (Baltimore) ; 100(20): e25952, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011074

RESUMO

BACKGROUND: Osteosarcoma represents the most common malignant bone tumor with high metastatic potential and inferior prognosis. RNA methylation (N6-methyladenosine [m6A]) is a prevalent RNA modification that epigenetically influences numerous biological processes including tumorigenesis. This study aims to determine that m6A regulators are significant biomarkers for osteosarcoma, and establish a prognostic model to predict the survival of patients. METHODS: In this study, we comprehensively analyzed the underlying associations between m6A regulators' mRNA expressions and metastasis as well as prognosis of osteosarcoma patients in the Cancer Genome Atlas. Multivariate Cox-regression analysis was used to screen regulators that were significantly associated with overall survival of osteosarcoma patients. Least absolute shrinkage and selection operator (LASSO) Cox-regression analysis was used for constructing m6A regulator-based osteosarcoma prognostic signature. RESULTS: Some of the regulators exhibited aberrant mRNA levels between osteosarcoma samples with and without metastasis. Multivariate Cox-regression analysis identified several regulators with potential prognostic significance. A risk score formula consisted of methyltransferase-like 3, YTH domains of Homo sapiens, and fat mass and obesity-associated protein was obtained through which patients could be prognostically stratified independently of potential confounding factors. The signature was also significantly associated with the metastatic potential of osteosarcoma. All the analyses could be well reproduced in another independent osteosarcoma cohort from the Gene Expression Omnibus. CONCLUSIONS: In conclusion, this study first revealed potential roles of m6A regulators in osteosarcoma metastasis and prognosis, which should be helpful for its clinical decision-making.


Assuntos
Biomarcadores Tumorais/genética , Osteossarcoma/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/análise , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Conjuntos de Dados como Assunto , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metilação , Metiltransferases/análise , Metiltransferases/genética , Metiltransferases/metabolismo , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Osteossarcoma/mortalidade , Osteossarcoma/secundário , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Processamento de RNA/análise , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , RNA-Seq
20.
Medicine (Baltimore) ; 100(20): e25994, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011092

RESUMO

ABSTRACT: In precision oncology, immune check point blockade therapy has quickly emerged as novel strategy by its efficacy, where programmed death ligand 1 (PD-L1) expression is used as a clinically validated predictive biomarker of response for the therapy. Automating pathological image analysis and accelerating pathology evaluation is becoming an unmet need. Artificial Intelligence and deep learning tools in digital pathology have been studied in order to evaluate PD-L1 expression in PD-L1 immunohistochemistry image. We proposed a Dual-scale Categorization (DSC)-based deep learning method that employed 2 VGG16 neural networks, 1 network for 1 scale, to critically evaluate PD-L1 expression. The DSC-based deep learning method was tested in a cohort of 110 patients diagnosed as non-small cell lung cancer. This method showed a concordance of 88% with pathologist, which was higher than concordance of 83% of 1-scale categorization-based method. Our results show that the DSCbased method can empower the deep learning application in digital pathology and facilitate computer-aided diagnosis.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Diagnóstico por Computador/métodos , Neoplasias Pulmonares/diagnóstico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Aprendizado Profundo , Regulação Neoplásica da Expressão Gênica , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imuno-Histoquímica , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Seleção de Pacientes , Medicina de Precisão/métodos
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