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1.
Sci Rep ; 14(1): 1568, 2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238494

RESUMO

This study aimed to develop and validate prognostic nomograms that can estimate the probability of 1-, 3- and 5-year overall survival (OS) as well as cancer-specific survival (CSS) for Intrahepatic cholangiocarcinoma (ICCA) patients. Clinical data of 1446 patients diagnosed with ICCA between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. In both the OS and the CSS group, the training cohort and validation cohort were divided into a 7:3 ratio. Age, sex, AJCC T stage, AJCC N stage, AJCC M stage, surgical status, and tumor grade were selected as independent prognostic risk factors to build the nomograms. To compare the efficacy of predicting 1-, 3-, and 5-year OS and CSS rates of the nomogram with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, we evaluated the Harrell's index of concordance (C-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) in both cohorts. The results showed the nomogram for 1-, 3-, and 5-year OS and CSS prediction performed better than the AJCC staging system. In the subgroup analysis for patients could not receive surgery as the primary treatment. We developed two nomograms for predicting the 1-, and 2-year OS and CSS rates following the same analysis procedure. Results indicate that the performance of both nomograms, which contained sex, AJCC T stage, AJCC M stage, chemotherapy, and tumor grade and prognostic factors, was also superior to the AJCC staging system. Meanwhile, four dynamic network-based nomograms were published. The survival analysis showed the survival rate of patients classified as high-risk based on the nomogram score was significantly lower compared to those categorized as low-risk (P < 0.0001). Finally, accurate and convenient nomograms were established to assist clinicians in making more personalized prognosis predictions for ICCA patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Nomogramas , Colangiocarcinoma/cirurgia , Fatores de Risco , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Internet , Programa de SEER , Prognóstico , Estadiamento de Neoplasias
2.
Int J Surg ; 110(3): 1699-1710, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38181123

RESUMO

Various immunotherapy has been greatly applied to comprehensive treatment of malignant cancer under different degrees of tumor burden. Scientific researchers have gained considerable progress in the relationship between immunotherapy and tumor burden in recent years. This review aimed to explore the prospect and developing trends in the field of tumor burden and immunotherapy from a bibliometric perspective. Articles about tumor burden and immunotherapy were collected from the Web of Science Core Collection (WoSCC) (retrieved on 3 January 2023). The R package 'Bibliometrix' analyzed the primary bibliometric features and created a three-filed plot to display the relationship between institutions, countries, and keywords. VOSviewer was used for co-authorship analysis, co-occurrence analysis, and their visualization. And CiteSpace calculated the citation burst references and keywords. A total of 1030 publications were retrieved from 35 years of scientific researches. The United States (US) and China published the most articles. The most productive journals were Cancer Immunology Immunotherapy and Journal for ImmunoTherapy of Cancer . The top one institution of the highest output was University of Texas MD Anderson Cancer Center. The hot keywords of strong citation burst strength in recent years were 'nivolumab', 'tumor microenvironment', and 'immune checkpoint inhibitor'. The most popular tumor type is melanoma. This bibliometric analysis mapped a basic knowledge structure. The field of tumor burden and immunotherapy is entering a rapid growing stage and keeping it value for future research.


Assuntos
Imunoterapia , Melanoma , Humanos , Carga Tumoral , Autoria , Bibliometria , Microambiente Tumoral
3.
Eur J Med Res ; 28(1): 229, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37430294

RESUMO

BACKGROUND: As the complexity and diversity of the tumor immune microenvironment (TIME) are becoming better understood, burgeoning research has progressed in this field. However, there is a scarcity of literature specifically focused on the bibliometric analysis of this topic. This study sought to investigate the development pattern of TIME-related research from 2006 to September 14, 2022, from a bibliometric perspective. METHODS: We acquired both articles and reviews related to TIME from the Web of Science Core Collection (WoSCC) (retrieved on September 14, 2022). R package "Bibliometrix" was used to calculate the basic bibliometric features, present the collaborative conditions of countries and authors, and generate a three-field plot to show the relationships among authors, affiliations, and keywords. VOSviewer was utilized for co-authorship analysis of country and institution and keyword co-occurrence analysis. CiteSpace was used for citation burst analysis of keywords and cited references. In addition, Microsoft Office Excel 2019 was used to develop an exponential model to fit the cumulative publication numbers. RESULTS: A total of 2545 publications on TIME were included, and the annual publication trend exhibited a significant increase over time. China and Fudan University were the most productive country and institution, with the highest number of publications of 1495 and 396, respectively. Frontiers in Oncology held the highest number of publications. A number of authors were recognized as the main contributors in this field. The clustering analysis revealed six clusters of keywords that highlighted the research hot spots in the fields of basic medical research, immunotherapy, and various cancer types separately. CONCLUSIONS: This research analyzed 16 years of TIME-related research and sketched out a basic knowledge framework that includes publications, countries, journals, authors, institutions, and keywords. The finding revealed that the current research hot spots of the TIME domain lie in "TIME and cancer prognosis", "cancer immunotherapy", and "immune checkpoint". Our researchers identified the following areas: "immune checkpoint-based immunotherapy", "precise immunotherapy" and "immunocyte pattern", which may emerge as frontiers and focal points in the upcoming years, offering valuable avenues for further exploration.


Assuntos
Pesquisa Biomédica , Dermatite , Humanos , Bibliometria , China , Imunoterapia
4.
Quant Imaging Med Surg ; 13(6): 3902-3914, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37284072

RESUMO

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

5.
Front Oncol ; 13: 1279766, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38357423

RESUMO

Background: Primary gallbladder gastrinoma is an exceptionally uncommon tumor and is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma and rare cases of primary gastrinoma from the biliary system have been reported. Case presentation: We report a case of a 50-year-old woman with watery diarrhea who intermittently received proton pump inhibitors (PPIs) as treatment. A serum gastrin level of 711 pg/ml was recorded after the withdrawal of PPI over 1 week. Enhanced computed tomography (CT) imaging and octreotide imaging uncovered a solitary tumor at the hepatic hilar region. During the laparoscopic surgery, it was determined that the tumor had its origin in the wall of the gallbladder neck, prompting the implementation of a laparoscopic cholecystectomy. Histological analysis revealed a primary neuroendocrine tumor from the neck of the gallbladder. The patient's symptoms disappeared after the surgery with a follow-up of 6 months. Conclusions: This case confirmed that primary gallbladder gastrinoma represents a distinct nosological entity. Immunohistochemical analysis plays a pivotal role in the diagnostic process. Given the limited understanding of primary gallbladder gastrinoma, our objective is to offer novel insights into this rare disease by delivering distinctive information and highlighting the therapeutic significance of surgical intervention.

6.
Front Immunol ; 13: 1096806, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36591239

RESUMO

Background: Despite providing clinical benefit, immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in a number of patients. This study explored the development pattern in irAEs research from a bibliometric perspective. Methods: We obtained articles and reviews related to irAEs from the Web of Science Core Collection (WoSCC) (retrieved on September 13, 2022). Using the R package "Bibliometrix", the main bibliometric features were calculated, and a three-filed plot was generated to show the relationship between authors, institutions, and topics. VOSviewer was used for co-authorship and keyword co-occurrence analysis and visualization. CiteSpace was used to detect burst references and keywords. Results: A total of 3995 publications on irAEs were included. The United States (US), Japan, and China had the highest publications. The Journal for ImmunoTherapy of Cancer had the highest number of publications. In addition to "immune-related adverse events", "immune checkpoint inhibitors", "immunotherapy", and "nivolumab" were the most frequently used keywords. Conclusions: A bibliometric analysis of 17 years of irAEs research was conducted to map a basic knowledge structure including countries, institutions, authors, journals, and publications. The findings provided a comprehensive perspective on the broad future of this research area.


Assuntos
Autoria , Bibliometria , Humanos , China , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia
8.
Int Immunopharmacol ; 90: 107164, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33172741

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy exhibiting the highest lethality. The present study aimed to identify different immune-related clusters in HCC and a robust tumor gene signature to facilitate the prognosis prediction for HCC patients. METHODS: For the 375 HCC cases collected from the dataset of Cancer Genome Atlas (TCGA), their overall survival (OS) and immune-related genes (IRGs) expression patterns were collected. Thereafter, consensus clustering was employed for grouping and functional enrichment, whereas the ESTIMATE algorithm and the CIBERSORT algorithm were used in subsequent assessment. Immunohistochemistry (IHC) was conducted to verify the protein expression of model genes in HCC and adjacent tissues. RESULTS: According to consensus clustering with 93-survival related IRGs, a total of five subgroups were found. These five clusters had different prognoses, immune statuses, and expression of immune checkpoints. Afterwards, 11 genes were enrolled for constructing the OS-related prediction model for TCGA HCC cases, which was then validated using the database of International Cancer Genome Consortium (ICGC). The protein expression of LCN2, S100A10, FABP6, PLXNA1, KITLG and OXTR were enhanced in HCC tissues relative to that in normal hepatic tissues, while the protein expression of S100A1, CCL26, CMTM4, IL1RN and RARG were reduced in HCC compared with normal tissues. In addition, different immunocyte infiltration levels between low- and high- groups were further examined. CONCLUSIONS: According to our results, the IRGs-based classifications assist in explaining the HCC heterogeneity, which may help to develop the more efficient individualized treatments.


Assuntos
Carcinoma Hepatocelular/genética , Bases de Dados Genéticas/estatística & dados numéricos , Perfilação da Expressão Gênica/métodos , Prognóstico , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Biologia Computacional , Conjuntos de Dados como Assunto , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Transcriptoma
9.
Aging (Albany NY) ; 13(2): 2626-2639, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33318318

RESUMO

We aimed to investigate whether lncRNA CYTOR could sponge miR-125b-5p to affect hepatocellular carcinoma (HCC) cells through targeting KIAA1522. The expression of CYTOR, miR-125b-5p and KIAA1522 in HCC cells was detected by Real-time quantitative polymerase chain reaction (RT-qPCR) analysis. KIAA1522 expression in HCC tissues was detected by immunohistochemistry. The proliferation, cell cycle and apoptosis of HCC cells after transfection were respectively detected by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, and related protein expression was determined by Western blot analysis. As a result, The Cancer Genome Atlas (TCGA) database indicated that expression of CYTOR and KIAA1522 was increased in HCC tissues and high expression of CYTOR and KIAA1522 was related to worse overall survival. MiR-125b-5p expression was decreased in HCC tissues, which was negatively correlated with the expression of CYTOR and KIAA1522. The proliferation and cell cycle of HCC cells were suppressed by CYTOR interference while promoted by miR-125b-5p interference and KIAA1522 overexpression. The apoptosis of HCC cells was promoted by CYTOR interference while inhibited by miR-125b-5p interference and KIAA1522 overexpression. In conclusion, CYTOR interference suppressed the proliferation and cell cycle, and promoted the apoptosis of HCC cells by regulating the miR-125b-5p/KIAA1522 axis.


Assuntos
Apoptose/genética , Carcinoma Hepatocelular/genética , Ciclo Celular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética
10.
J Hepatocell Carcinoma ; 7: 315-330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204664

RESUMO

BACKGROUND: It has been widely suggested that the association of hypoxia with the immune status within the microenvironment of hepatocellular carcinoma (HCC) is of great clinical significance. The present work was carried out aiming to establish the hypoxia-related and immune-associated gene signature to stratify the risks in HCC. PATIENTS AND METHODS: The ssGSEA and t-SNE algorithms were utilized to estimate the immune and hypoxia statuses, respectively, using the TCGA database-derived cohort transcriptome profiles. Different immune groups are distinguished according to the ssGSEA scores, while the hypoxia-high and -low groups are inferred based on the distinct overall survival (OS) of the two groups of patients. Moreover, prognostic genes were identified using the Cox regression model in combination with the LASSO approach, which were later used to establish the hypoxia-related and immune-associated gene signature. At the same time, an ICGC cohort was used for external validation. RESULTS: A total of 13 genes, namely, HAVCR1, PSRC1, CCNJL, PDSS1, MEX3A, EID3, EPO, PLOD2, KPNA2, CDCA8, ADAMTS5, SLC1A7 and PIGZ, were discovered by the LASSO approach for constructing a gene signature to stratify the risk of HCC. Those low-risk cases showed superior prognosis (OS) to the high-risk counterparts (p<0.05). Moreover, it was suggested by multivariate analysis that our constructed hypoxia-related and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p<0.001). Patients in high-risk groups had severe hypoxia, higher immune checkpoint expression such as PD-L1, and different immunocyte infiltration states (eg, higher infiltration of regulatory T cells in the high-risk group) compared with those low-risk patients. CONCLUSION: Our as-constructed hypoxia-related and immune-associated prognosis signature can be used as an approach to stratify the risk of HCC.

11.
World J Gastroenterol ; 26(41): 6414-6430, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33244202

RESUMO

BACKGROUND: Gastric cancer (GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early stages. AIM: To identify the specific deoxyribonucleic acid (DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA methylation. METHODS: Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this model. RESULTS: Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper- or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio (HR) = 2.24, 95% confidence interval (CI): 1.28-3.92, P < 0.001] and test (HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) datasets. CONCLUSION: DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.


Assuntos
Neoplasias Gástricas , DNA , Metilação de DNA , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/genética
12.
World J Gastrointest Oncol ; 12(9): 1014-1030, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33005295

RESUMO

BACKGROUND: Gallbladder carcinoma (GBC) carries a poor prognosis and requires a prediction method. Gamma-glutamyl transferase-to-platelet ratio (GPR) is a recently reported cancer prognostic factor. Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear, studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases. AIM: To assess the prognostic value of GPR and to design a prognostic nomogram for GBC. METHODS: The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017. The patients were stratified into a high- or low-GPR group. The predictive ability of GPR was evaluated by Kaplan-Meier analysis and a Cox regression model. We developed a nomogram based on GPR, which we verified using calibration curves. The nomogram and other prognosis prediction models were compared using time-dependent receiver operating characteristic curves and the concordance index. RESULTS: Patients in the high-GPR group had a higher risk of jaundice, were older, and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes. Univariate analysis revealed that GPR, age, body mass index, tumor-node-metastasis (TNM) stage, jaundice, cancer cell differentiation degree, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival (OS). Multivariate analysis confirmed that GPR, body mass index, age, and TNM stage were independent predictors of poor OS. Calibration curves were highly consistent with actual observations. Comparisons of time-dependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging. CONCLUSION: GPR is an independent predictor of GBC prognosis, and nomogram-integrated GPR is a promising predictive model for OS in GBC.

13.
Cancer Med ; 9(20): 7646-7662, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32813933

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. We aimed to identify a robust lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients. METHODS: We analyzed the gene expression profiles of lipid metabolism from Molecular Signatures Database and information of patients from The Cancer Genome Atlas. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and principal component analysis (PCA) were employed for functional annotation. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to verify the expression of model genes in HCC and adjacent tissues. RESULTS: As a result, a lipid metabolism-related signature consisting of acyl-CoA synthetase long-chain family member 6 (ACSL6), lysophosphatidylcholine acyltransferase 1, phospholipase A2 group 1B, lecithin-cholesterol acyltransferase (LCAT), and sphingomyelin phosphodiesterase 4 (SMPD4) was identified among HCC patients. Lysophosphatidylcholine acyltransferase 1, PLA2G1B, and SMPD4 were proved significantly high expression while ACSL6 and LCAT were remarkably low expression in our 15 pairs of matched HCC and normal tissues by qRT-PCR. Under different conditions, the overall survival (OS) of patients in low-risk group was prolonged than that in high-risk group. Moreover, the as-constructed signature was an independent factor, which was remarkably associated with gender, histologic grade, and platelet level of HCC patients. In addition, the receiver operating characteristic (ROC) curve analysis confirmed the good potency of the model. Functional enrichment analysis further revealed that lower fatty acid (FA) oxidation and higher infiltration of immunocytes were detected in patients from the high-risk group compared with those in the low-risk group. CONCLUSIONS: Our findings indicate that the lipid metabolism-related signature shows prognostic significance for HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Suscetibilidade a Doenças , Metabolismo dos Lipídeos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/mortalidade , Estudos de Casos e Controles , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Prognóstico , Curva ROC , Transcriptoma
15.
Aging (Albany NY) ; 12(6): 5010-5030, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191631

RESUMO

Liver hepatocellular carcinoma (LIHC), an inflammation-associated cancer induced by a variety of etiological factors, is still one of the most prevalent and lethal cancers in human population. In this study, the expression profiles of immune-related genes (IRGs) were integrated with the overall survival (OS) of 378 LIHC patients based on the Cancer Genome Atlas (TCGA) dataset. Moreover, the differentially expressed and survival related IRGs among LIHC patients were predicted through the computational difference algorithm and COX regression analysis. As a result, 7 genes, including HSPA4, S100A10, FABP6, CACYBP, HDAC1, FCGR2B and SHC1, were retrieved to construct a predictive model associated with the overall survival (OS) of LIHC patients. Typically, the as-constructed model performed moderately in predicting prognosis, which was also correlated with tumor grade. Functional enrichment analysis revealed that the genes of high-risk group were actively involved in mRNA binding and the spliceosome pathway. Intriguingly, the prognostic index established based on IRGs reflected infiltration by multiple types of immunocytes. Our findings screen several IRGs with clinical significance, reveal the drivers of immune repertoire, and illustrate the importance of a personalized, IRG-based immune signature in LIHC recognition, surveillance, and prognosis prediction.


Assuntos
Carcinoma Hepatocelular/imunologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Prognóstico
16.
Cell Prolif ; 53(4): e12791, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32162380

RESUMO

Hepatocellular carcinoma (HCC) is a primary liver malignancy with a high global prevalence and a dismal prognosis. Studies are urgently needed to examine the molecular pathogenesis and biological characteristics of HCC. Chromatin remodelling, an integral component of the DNA damage response, protects against DNA damage-induced genome instability and tumorigenesis by triggering the signalling events that activate the interconnected DNA repair pathways. The SWI/SNF complexes are one of the most extensively investigated adenosine triphosphate-dependent chromatin remodelling complexes, and mutations in genes encoding SWI/SNF subunits are frequently observed in various human cancers, including HCC. The mutated SWI/SNF complex subunits exert dual functions by accelerating or inhibiting HCC initiation and progression. Furthermore, the abnormal SWI/SNF complexes influence the transcription of interferon-stimulated genes, as well as the differentiation, activation and recruitment of several immune cell types. In addition, they exhibit synergistic effects with immune checkpoint inhibitors in the treatment of diverse tumour types. Therefore, understanding the mutations and deficiencies of the SMI/SNF complexes, together with the associated functional mechanisms, may provide a novel strategy to treat HCC through targeting the related genes or modulating the tumour microenvironment.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Mutação , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Animais , Carcinogênese/genética , Carcinogênese/imunologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Montagem e Desmontagem da Cromatina , Dano ao DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Regulação Neoplásica da Expressão Gênica , Instabilidade Genômica , Humanos , Imunidade , Imunoterapia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Proteínas Nucleares/imunologia , Fatores de Transcrição/imunologia
17.
Cell Prolif ; 53(3): e12772, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32003505

RESUMO

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high worldwide prevalence and poor prognosis. Researches are urgently needed on its molecular pathogenesis and biological characteristics. Metabolic reprogramming for adaptation to the tumour microenvironment (TME) has been recognized as a hallmark of cancer. Dysregulation of lipid metabolism especially fatty acid (FA) metabolism, which involved in the alternations of the expression and activity of lipid-metabolizing enzymes, is a hotspot in recent study, and it may be involved in HCC development and progression. Meanwhile, immune cells are also known as key players in the HCC microenvironment and show complicated crosstalk with cancer cells. Emerging evidence has shown that the functions of immune cells in TME are closely related to abnormal lipid metabolism. In this review, we summarize the recent findings of lipid metabolic reprogramming in TME and relate these findings to HCC progression. Our understanding of dysregulated lipid metabolism and associated signalling pathways may suggest a novel strategy to treat HCC by reprogramming cell lipid metabolism or modulating TME.


Assuntos
Carcinoma Hepatocelular/metabolismo , Metabolismo dos Lipídeos , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Humanos , Imunidade Celular , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/patologia
18.
World J Gastroenterol ; 25(39): 6016-6024, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660037

RESUMO

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been adopted by liver surgeons in recent years. However, high morbidity and mortality rates have limited the promotion of this technique. Some recent studies have suggested that ALPPS with a partial split can effectively induce the growth of future liver remnant (FLR) similar to a complete split with better postoperative safety profiles. However, some others have suggested that ALPPS can induce more rapid and adequate FLR growth, but with the same postoperative morbidity and mortality rates as in partial split of the liver parenchyma in ALPPS (p-ALPPS). AIM: To perform a systematic review and meta-analysis on ALPPS and p-ALPPS. METHODS: A systematic literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was performed for articles published until June 2019. Studies comparing the outcomes of p-ALPPS and ALPPS for a small FLR in consecutive patients were included. Our main endpoints were the morbidity, mortality, and FLR hypertrophy rates. We performed a subgroup analysis to evaluate patients with and without liver cirrhosis. We assessed pooled data using a random-effects model. RESULTS: Four studies met the inclusion criteria. Four studies reported data on morbidity and mortality, and two studies reported the FLR hypertrophy rate and one study involved patients with cirrhosis. In the non-cirrhotic group, p-ALPPS-treated patients had significantly lower morbidity and mortality rates than ALPPS-treated patients [odds ratio (OR) = 0.2; 95% confidence interval (CI): 0.07-0.57; P = 0.003 and OR = 0.16; 95%CI: 0.03-0.9; P = 0.04]. No significant difference in the FLR hypertrophy rate was observed between the two groups (P > 0.05). The total effects indicated no difference in the FLR hypertrophy rate or perioperative morbidity and mortality rates between the ALPPS and p-ALPPS groups. In contrast, ALPPS seemed to have a better outcome in the cirrhotic group. CONCLUSION: The findings of our study suggest that p-ALPPS is safer than ALPPS in patients without cirrhosis and exhibits the same rate of FLR hypertrophy.


Assuntos
Hepatectomia/métodos , Hepatomegalia/epidemiologia , Regeneração Hepática , Veia Porta/cirurgia , Complicações Pós-Operatórias/epidemiologia , Hepatectomia/efeitos adversos , Hepatomegalia/etiologia , Humanos , Ligadura/efeitos adversos , Ligadura/métodos , Fígado/irrigação sanguínea , Fígado/fisiologia , Fígado/cirurgia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Análise de Sobrevida , Resultado do Tratamento
19.
Med Oncol ; 36(11): 94, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605245

RESUMO

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a variety of solid tumors; nonetheless, they have not been well investigated and are still recognized as a relative contraindication for patients with a liver transplantation (LT) history, since ICIs treatment might potentially lead to graft rejection. The program death-1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways are implicated in the tolerance of transplanted organ, as well as blockade of the pathways, which contribute to eliminating tumors and may inadvertently lead to peripheral transplant rejection. Currently, no guidelines are available regarding the treatment for ICIs patients with a prior LT history. Therefore, this study was carried out to review the recent studies, attempting to introduce the ICIs-related graft rejection after LT from various aspects. We believed that ICIs could be given for the well-informed patients receiving LT and developed recurrence in a controlled setting. Typically, these patients should be treated according to a clinical care path or a prospective clinical trial, so as obtain a persistent anti-tumor immune response in the meantime of avoiding graft rejection, adjust the immunosuppression, reduce the possibility of graft loss following rejection, and have the opportunity to develop biomarkers for tumor response and transplant rejection.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Transplante de Fígado , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Rejeição de Enxerto/imunologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
20.
World J Clin Cases ; 7(11): 1330-1336, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31236397

RESUMO

BACKGROUND: Sarcomatoid hepatocellular carcinoma (SHC) combined with paraneoplastic leukemoid reaction (PLR), which is associated with a poor prognosis, is rarely seen in the clinic. Here, we report the case of a patient in the above situation. CASE SUMMARY: A 75-year-old female patient with a past medical history of hypertension and cerebral infarction paid a hospital visit as a result of right upper quadrant abdominal pain and anorexia for two months. Laboratory examination revealed a white blood cell (WBC) count of 43790/µL, which was then increased up to 77050/µL. In addition, the results of bone marrow examination suggested a leukemoid reaction. Computed tomography (CT) revealed a focal hepatic mass, which was confirmed through pathological examination to be an SHC postoperatively. In addition, the WBC count had fallen to a normal level before she left the hospital. However, the patient died two and a half months after the second hospital admission. CONCLUSION: This is a rare case of SHC combined with PLR, both of which have an extremely poor prognosis.

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