scholarly journals TREM2 is a prognostic biomarker and correlates in immune infiltrates in kidney renal papillary cell carcinoma and liver hepatocellular carcinoma

2021 ◽  
Author(s):  
bin wen Xiang ◽  
Sha Fang ◽  
peng yan Ding ◽  
min nuo Liu ◽  
chao hua Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Mrna Levels ◽  
Limited Information ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Positive Correlations ◽  
Liver Hepatocellular Carcinoma ◽  
Infiltrating Lymphocytes

Abstract Background: TREM2 was identified as a marker for tumor-associated macrophages (TAMs) and monocytes. However, there is limited information concerning the TREM2 mRNA levels correlated with the outcome and tumor-infiltrating lymphocytes in different cancers.Methods: To explore the expression pattern and prognostic value of TREM2 in pan-cancer, We use multiple databases, including ONCOMINE, PrognoScan, Kaplan-Meier Plotter, GEPIA, and TIMER. we investigated the correlations between TREM1 expression and immune infiltration in cancers, especially kidney renal papillary cell carcinoma (KIRP), and liver hepatocellular carcinoma (LIHC)Results: According to the results from Oncomine and TIMER datasets, in a general way, TREM2 mRNA expression is higher in the majority of the tumor and is lower in lung cancer, compared with normal adjacent tissues. A high expression level of TREM2 was beneficial to the survival of LIHC patients. Both in KIRP and LIHC, TREM2 expression levels showed significant positive correlations with infiltrating levels of macrophages and dendritic cells. It also correlated with diverse immune marker sets. We can also find that TREM2 expression was modestly associated with CD8+T cells in KIRP. However, it is related to the Treg in LIHC.Conclusions: TREM2 may be a prognostic marker in the multitudinous tumor. Furthermore, TREM2 may interact with immune infiltration to influence patient survival in cancers like LIHC and KIRP.

scholarly journals Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

2021 ◽  
Vol 11 ◽  
Author(s):  
Chuanxi Yang ◽  
Tingting Wu ◽  
Jing Zhang ◽  
Jinhui Liu ◽  
Kun Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Carcinoma ◽  
Marker Gene ◽  
Gene Marker ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Positive Correlations ◽  
Liver Hepatocellular Carcinoma ◽  
Pan Cancer

BackgroundNAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.MethodsIn this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2.ResultsCompared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.ConclusionNAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

scholarly journals Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

2020 ◽  
Author(s):  
Chuanxi Yang ◽  
Tingting Wu ◽  
Jing Zhang ◽  
Jinghui Liu ◽  
Kun Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Carcinoma ◽  
Marker Gene ◽  
Gene Marker ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Positive Correlations ◽  
Liver Hepatocellular Carcinoma ◽  
Pan Cancer

Abstract BackgroundNAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.MethodsIn this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA.ResultsCompared with normal tissues, NAT10 showed higher expression in 26 of 27 cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.ConclusionNAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.

scholarly journals Nuclear Respiratory Factor 1 Associated with Prognosis and Immune Infiltration in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Dan Wang ◽  
Linlin Huang ◽  
Xiaojing Zhang ◽  
Pingping Sun ◽  
Yapeng Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Chronic Hepatitis ◽  
Mrna Expression ◽  
Tumor Infiltrating Lymphocytes ◽  
Cox Regression Analysis ◽  
Nuclear Respiratory Factor ◽  
Immune Infiltration ◽  
Nuclear Respiratory Factor 1 ◽  
Infiltrating Lymphocytes

Abstract Background: Recent studies have shown that functional mitochondria are essential for cancer cells. Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates mitochondrial biogenesis and the expression of the respiratory chain, but little is known about its prognostic value and tumor-infiltrating lymphocytes association. Here, we evaluated the association among expression of NRF1, clinicopathological characteristics, survival and immune infiltration in hepatocellular carcinoma (HCC).Methods: We used the Tumor Immune Estimation Resource (TIMER) to analyze the difference of NRF1 mRNA expression in human cancers. Clinical-pathological information and follow-up data were collected from HCC (n = 171) and chronic hepatitis (n = 113) patients. NRF1 expression were scored based on the percentage and intensity of immunohistochemical staining in pathological slides. Correlations between clinical features and the expression of NRF1 were evaluated by Chi-square test, Kaplan-Meier curves, logrank tests and multivariate Cox regression analysis. The correlations between NRF1 expression and gene marker sets of tumor infiltrating lymphocytes (TILs) were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Results: NRF1 mRNA expression was significantly higher in HCC than in normal tissue. Compared with chronic hepatitis, more frequency of NRF1 high expression are found in HCC (31.58 % vs 13.27 %, P < 0.001, P < 0.001). In addition, the NRF1 expression was significantly associated with hepatic cirrhosis (P = 0.021) and vascular invasion (P = 0.025). NRF1 expression was also a significant independent predictor of survival in HCC (P = 0.003; HRadj = 0.20; 95% CI = 0.09 – 0.44). NRF1 showed positively correlated with TILs, including B cell (r = 0.384, P = 1.68e-13), CD8+ T cells (r = 0.246, P = 3.99e-06), CD4+ T cells (r = 0.535, P = 6.90e-27), macrophage (r = 0.506, P = 1.52e-23), neutrophils (r = 0.465, P = 6.08e-20) and dendritic cell (r = 0.404, P = 8.61e-15). The marker genes of TILs correlated significantly with NRF1 expression.Conclusions: NRF1 expression was a useful independent prognostic factor and correlated with tumor immune infiltration in HCC.

Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection

2007 ◽  
Vol 25 (18) ◽  
pp. 2586-2593 ◽  
Author(s):  
Qiang Gao ◽  
Shuang-Jian Qiu ◽  
Jia Fan ◽  
Jian Zhou ◽  
Xiao-Ying Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Cox Regression ◽  
Independent Predictor ◽  
Cytotoxic T Cells ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Kaplan Meier ◽  
Infiltrating Lymphocytes

Purpose To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. Patients and Methods CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. Results CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8+ cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P < .0001). Five-year OS and DFS rates were only 24.1% and 19.8% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0% and 59.4% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P = .032) and presence of tumor vascular invasion (P = .031). Conclusion Tregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery.

Multi-factor Evaluation of Tumor-infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma and its Prognostic Value

2021 ◽  
Author(s):  
susheng miao ◽  
xueying wang ◽  
Erliang Guo ◽  
Lunhua Guo ◽  
Changming An ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Tumor Infiltrating Lymphocytes ◽  
Clinicopathological Characteristics ◽  
Kaplan Meier ◽  
Factor Evaluation ◽  
Infiltrating Lymphocytes

Abstract Background: Laryngeal squamous cell carcinoma (LSCC) is a heterogeneous disease. In clinical practice, patients with similar clinicopathological characteristics often show different outcomes. This study evaluated the levels of primary LSCC intratumoral infiltrating lymphocytes (iTILs), tumor-infiltrating lymphocyte volume (TILV), frontier tumor-infiltrating lymphocytes (fTILs), and their relations to the patient's clinical outcome. Materials and methods: According to the 2017 study of the International TILs Working Group, hematoxyline and eosin-stained slides from 412 patients were evaluated for their morphology of tumor immune infiltration status.Results: Kaplan-Meier analysis showed that high levels of iTILs, TILV, and fTILs were significantly correlated with OS (all P<0.05). Cox regression model analysis showed that high levels of iTILs, TILV, and fTILs were independently associated with better OS (all P<0.05). Conclusion: Local inflammatory markers in patients with laryngeal squamous cell carcinoma, especially the levels of iTILs, TILV, and fTILs, are reliable prognostic factors.

scholarly journals Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma

2015 ◽  
Vol 22 (3) ◽  
pp. 704-713 ◽  
Author(s):  
Maria Vassilakopoulou ◽  
Margaritis Avgeris ◽  
Vamsidhar Velcheti ◽  
Vassiliki Kotoula ◽  
Theodore Rampias ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Huijuan Ge ◽  
Yaoxin Xiao ◽  
Guangqi Qin ◽  
Yanzi Gu ◽  
Xu Cai ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Ovarian Clear Cell Carcinoma ◽  
Repair Deficiency ◽  
Ovarian Epithelial Carcinoma ◽  
Histological Characteristics ◽  
Infiltrating Lymphocytes

Abstract Background Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency. Methods A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays. Results dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %). Conclusions Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.

scholarly journals Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 486
Author(s):  
Juan P. Rodrigo ◽  
Mario Sánchez-Canteli ◽  
Fernando López ◽  
Gregory T. Wolf ◽  
Juan C. Hernández-Prera ◽  
...  
Keyword(s):  
Systematic Review ◽  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36–0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34–0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4–0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34–0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16–0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10–0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome.

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