scholarly journals Pan-Cancer Analysis Reveals FH as a Potential Prognostic and Immunological Biomarker in Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Heng Zhang ◽  
Qiang Ju ◽  
Jing Ji ◽  
Yanjie Zhao
Keyword(s):  
T Cells ◽  
Lung Adenocarcinoma ◽  
Tricarboxylic Acid Cycle ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Fumarate Hydratase ◽  
Lung Squamous Cell Carcinoma ◽  
Testicular Germ Cell ◽  
Cancer Types ◽  
Liver Hepatocellular Carcinoma

Fumarate hydratase (FH) is an important enzymatic component in the tricarboxylic acid cycle. Studies have reported that FH plays an important role in hereditary leiomyomatosis and renal cell cancer (HLRCC). However, the role of FH in human different cancers remains unknown. This study is aimed at analyzing the prognostic value of FH and demonstrating the correlation between FH expression and tumor immunity. Results showed that FH was mutated or copy number varied in 27 types of cancer. FH mRNA was abnormally upregulated across various cancers. Survival analysis suggested high expression of FH was associated with poor prognosis in many cancer types, including lung adenocarcinoma (LUAD). Additionally, FH expression was associated with immune infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, especially in liver hepatocellular carcinoma (LIHC), LUAD, and lung squamous cell carcinoma (LUSC). Moreover, FH expression showed a strong correlation with immune checkpoint markers in LUAD and testicular germ cell tumors (TGCT). These results indicate that FH is an immunotherapeutic target and a potential prognostic biomarker in LUAD.

Frequent expression of PD-L1 in testicular germ cell tumors.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 379-379 ◽  
Author(s):  
Christian Daniel Fankhauser ◽  
Alessandra Curioni Fontecedro ◽  
Joerg Beyer ◽  
Verena Tischler ◽  
Tullio Sulser ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Germ Cell ◽  
Single Case ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Germ Cell Cancer ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Major Interest

379 Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity . The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.

scholarly journals Expression and prognosis analysis of JMJD5 in human cancers

2020 ◽  
Author(s):  
Hui Li ◽  
Qun Li ◽  
Hong Jing ◽  
Jianghai Zhao ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Lung Adenocarcinoma ◽  
Immune Cells ◽  
Prognostic Value ◽  
Normal Tissues ◽  
Human Cancers ◽  
Stomach Adenocarcinoma ◽  
Liver Hepatocellular Carcinoma

Abstract BackgroundJumonjiC (JmjC) domain-containing protein 5 (JMJD5) plays an important role in cancer metabolism. However, the prognostic value of JMJD5 in most human cancers is still unknown. In this study, we aim to investigate the expression and prognostic value of JMJD5, immune cells infiltration, and the correlations among them. MethodsWe performed a detailed cancer vs. normal analysis of JMJD5 mRNA expression via online Tumor Immune Estimation Resource (TIMER). The protein expressions of JMJD5 in various cancers vs. adjacent normal tissues were examined by immunohistochemistry (IHC) of tissue microarray sections (TMAs). Moreover, the Kaplan-Meier Plotter databases were used to evaluate the prognostic values in above cancers. The correlations between JMJD5 expression level and abundances of six immune infiltrating cells (B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils and dendritic cells) were explored by TIMER database in breast cancer (BRCA), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and stomach adenocarcinoma (STAD). The prognostic values of tumor- infiltrating immune cells were also investigated by TIMER in above four cancers. Finally, the COX proportional hazards model was used to investigate the correlations among clinical outcome, the abundance of immune cell infiltrates and the expression of JMJD5 in above four cancer types.ResultsThe expression of JMJD5 was significantly lower in human breast carcinoma (BRCA), cholangiocarcinoma (CHOL), liver hepatocellular carcinoma (LIHC) and lung cancer (LUC) but higher in prostate adenocarcinoma (PRAD) and stomach adenocarcinoma (STAD) comparing to their respective normal tissues. And high expression of JMJD5 has better prognosis only in BRCA, LIHC, LUC but the opposite effect in STAD. JMJD5 expression is significant correlation with the abundance of six immune cells infiltration in above four cancers. Both the BRCA or lung adenocarcinoma (LUAD) patients with abundance of B cell and the STAD patients with low level of macrophage have a better cumulative survival. ConclusionsWe provided novel evidence of JMJD5 as an essential prognostic biomarker in cancers through analyses the correlation of the JMJD5 expression, tumor-infiltrating B cells and macrophages and prognostic value. This study offers new perspectives therapeutic target in BRCA, LUAD and STAD.

scholarly journals CENPF driven lung adenocarcinoma and lung squamous cell carcinoma with immune infiltrates

2020 ◽  
Author(s):  
Lei Li ◽  
Pengchao Zheng
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cd8 T Cells ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Marker

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods : CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5,P=0.01) and disease-free survival (DFS HR=1.4,P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS(OS HR=0.78,P=0.071) and DFS(DFS HR=1,P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

scholarly journals CENPF driven lung adenocarcinoma and lung squamous cell carcinoma with immune infiltrates

2020 ◽  
Author(s):  
Lei Li ◽  
Pengfei Zheng
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cd8 T Cells ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Marker

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods: CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5,P=0.01) and disease-free survival (DFS HR=1.4,P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS(OS HR=0.78,P=0.071) and DFS(DFS HR=1,P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

Sub-centimeter lymphadenopathy in germ cell testicular cancer: An ongoing surveillance challenge.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17011-e17011
Author(s):  
Ruth Kieran ◽  
Iseult Browne ◽  
John McCaffrey
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Specificity ◽  
Cancer Center ◽  
Correct Identification ◽  
Embryonal Tumors ◽  
Testicular Germ Cell ◽  
Landing Zone ◽  
Mixed Tumors

e17011 Background: Correct identification of retroperitoneal disease is essential for proper staging and management in germ cell tumors. A size threshold of a 10mm diameter has high specificity in assessing nodal metastases, but sensitivity can be poor at this level and many patients have sub-centimeter lymphadenopathy on post-orchidectomy staging. As many staging scans are done soon after surgery, these may represent reactive lymph nodes. We aimed to assess the prevalence of sub-centimeter lymphadenopathy on baseline imaging in our patients, and its association with recurrence. Methods: Records of patients diagnosed with testicular germ cell cancer in a tertiary cancer center (n = 55, 2015-2020) were reviewed (median followup of 26 months, range 1-59). Lymphadenopathy size measurements were taken from the scan report, which had been authorized by a radiology consultant. Results: Patients had a median age of 34 (range 19-63). 37 (67%) had pure seminomas, 2 (4%) pure embryonal tumors, 12 (22%) mixed tumors with a primarily (> 50%) embryonal component, and 4 (7%) other mixed types. 48 (87%) had stage 1 disease, 3 (6%) stage 2 and 4 (7%) stage 3 disease. 26 (47%) had CT staging preoperatively, of the remainder 69% (n = 20) were staged in the first 48 postoperative hours. 28 (51%) had no lymphadenopathy, 15 (27%) had sub-centimeter lymphadenopathy within the landing zone, 8 (15%) had lymphadenopathy measuring > 1 cm within the landing zone, 4 (7%) had lymphadenopathy elsewhere. 7 had immediate chemotherapy, 48 entered surveillance. For the 14 with sub-centimeter lymphadenopathy within the landing zone who did not have immediate chemotherapy, 3 regressed, 8 were stable. 2 underwent a PET for further assessment, 1 a biopsy. 3 increased in size. 6 patients on surveillance had a recurrence – of these 2 had seminomas with no baseline lymphadenopathy, 4 had mixed primarily embryonal tumors (3 with sub-centimeter lymphadenopathy (0.6, 0.7 and 0.9 cm each), one with a 1.3cm para-aortic lymph node). Of those 4, only 1 had significantly elevated HCG pre-operatively, all recurred in the sites of previously noted lymphadenopathy. Those with mixed, primarily embryonal disease with lymphadenopathy (representing 50% of such patients on surveillance) had a higher recurrence risk than other patients on surveillance (OR: 153, 95% CI 6-3709, p= 0.002) Those undergoing preoperative/delayed postoperative imaging (n = 28) were equally likely to have lymphadenopathy to those having imaging in the first 7 postoperative days ( X2 (3, N= 27) = 2.9, p= 0.4). 1 patient had died (unrelated causes), all others were disease-free at most recent followup. Conclusions: Sub-centimeter lymphadenopathy is more likely to be benign in those with seminomas, but even small volume lymphadenopathy in those with mixed tumors with a primarily embryonal component may represent metastatic disease, and should be monitored closely.

scholarly journals Overexpression of p75NTR in Human Seminoma: A New Biomarker?

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 629
Author(s):  
Anna Perri ◽  
Vittoria Rago ◽  
Rocco Malivindi ◽  
Lorenza Maltese ◽  
Danilo Lofaro ◽  
...  
Keyword(s):  
Human Cancer ◽  
Germ Cell Tumors ◽  
Receptor Protein ◽  
Specific Marker ◽  
Nuclear Staining ◽  
Trka Receptor ◽  
Testicular Germ Cell ◽  
Cancer Types ◽  
First Time

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.

Testicular Cancer

2017 ◽  
Author(s):  
Katherine A. McGlynn ◽  
Ewa Rajpert-De Meyts ◽  
Andreas Stang
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Developed Countries ◽  
Mortality Rates ◽  
Incidence Rates ◽  
European Ancestry ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Cancer Types

Testicular cancer is a rare cancer in the general population, but is the most common neoplasm among young men in many countries. It has one of the highest heritabilities of all cancer types. The vast majority of testicular cancers are germ cell tumors; thus the terms “testicular cancer” and “testicular germ cell tumors” (TGCTs) are often used interchangeably. Globally, the incidence of testicular cancer is highest among men of European ancestry and lowest among men of African and Asian ancestries. Incidence rates have been increasing in many countries since at least the mid-twentieth century. Mortality rates, however, have sharply declined in developed countries. While the reason for the decline in mortality rates is well known, reasons for the increase in incidence remain poorly understood. Accumulating evidence supports the hypothesis that most TGCTs are linked to disturbed development of the testes, beginning in utero, but fostered by postnatal events.

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