scholarly journals CCL20/TNF/VEGFA Cytokine Secretory Phenotype of Tumor-Associated Macrophages Is a Negative Prognostic Factor in Cutaneous Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3943
Author(s):  
Alba Gutiérrez-Seijo ◽  
Elena García-Martínez ◽  
Celia Barrio-Alonso ◽  
Miriam Pareja-Malagón ◽  
Alejandra Acosta-Ocampo ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Large Fraction ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Rna Seq ◽  
Primary Cutaneous Melanoma ◽  
Kaplan Meier ◽  
Intracellular Cytokines ◽  
Negative Prognostic Factor

TAMs constitute a large fraction of infiltrating immune cells in melanoma tissues, but their significance for clinical outcomes remains unclear. We explored diverse TAM parameters in clinically relevant primary cutaneous melanoma samples, including density, location, size, and polarization marker expression; in addition, because cytokine production is a hallmark of macrophages function, we measured CCL20, TNF, and VEGFA intracellular cytokines by single-cell multiparametric confocal microscopy. The Kaplan–Meier method was used to analyze correlation with melanoma-specific disease-free survival and overall survival. No significant correlations with clinical parameters were observed for TAM density, morphology, or location. Significantly, higher contents of the intracellular cytokines CCL20, TNF, and VEGFA were quantified in TAMs infiltrating metastasizing compared to non-metastasizing skin primary melanomas (p < 0.001). To mechanistically explore cytokine up-regulation, we performed in vitro studies with melanoma-conditioned macrophages, using RNA-seq to explore involved pathways and specific inhibitors. We show that p53 and NF-κB coregulate CCL20, TNF, and VEGFA in melanoma-conditioned macrophages. These results delineate a clinically relevant pro-oncogenic cytokine profile of TAMs with prognostic significance in primary melanomas and point to the combined therapeutic targeting of NF-kB/p53 pathways to control the deviation of TAMs in melanoma.

Prognostic Significance of Nuclear Receptor Coactivator-3 Overexpression in Primary Cutaneous Melanoma

2006 ◽  
Vol 24 (28) ◽  
pp. 4565-4569 ◽  
Author(s):  
Javier Rangel ◽  
Sima Torabian ◽  
Ladan Shaikh ◽  
Mehdi Nosrati ◽  
Frederick L. Baehner ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Nuclear Receptor ◽  
Cutaneous Melanoma ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Primary Cutaneous Melanoma ◽  
Nuclear Receptor Coactivator ◽  
Kaplan Meier ◽  
The Impact

Purpose To assess the prognostic significance of nuclear receptor coactivator-3 (NCOA3) overexpression in primary cutaneous melanoma. Patients and Methods NCOA3 expression was assessed using immunohistochemical analysis of a melanoma tissue microarray (TMA) containing primary melanomas from 343 patients with defined histology and follow-up. The impact of the presence or absence of various prognostic factors on relapse-free survival (RFS) and disease-specific survival (DSS) of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. The impact of presence or absence of various factors on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. Results Increasing degree of NCOA3 expression was significantly predictive of SLN metastasis (P = .013) and the mean number of SLN metastases (P = .031). Kaplan-Meier analysis demonstrated a significant association between NCOA3 overexpression and reduced RFS (P = .021) and DSS (P = .030). Logistic regression analysis revealed increasing degree of NCOA3 expression to be an independent predictor of SLN status (P = .017). Multivariate Cox regression analysis showed the independent impact of NCOA3 expression on RFS (P = .0095) and DSS (P = .021). NCOA3 was the most powerful factor predicting DSS, outperforming tumor thickness and ulceration. Conclusion These results identify NCOA3 as a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS, and DSS.

Prognostic Significance of Tumor Infiltrating Lymphocytes in Melanoma

2011 ◽  
Vol 77 (2) ◽  
pp. 188-192 ◽  
Author(s):  
Alison L. Burton ◽  
Brent A. Roach ◽  
Michael P. Mays ◽  
Andrea F. Chen ◽  
Brooke A.R. Ginter ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Survival ◽  
Kaplan Meier ◽  
Major Predictor ◽  
Significant Independent Factor ◽  
Infiltrating Lymphocytes

The prognostic significance of tumor infiltrating lymphocyte (TIL) response in cutaneous melanoma is controversial. This analysis of data from a prospective, randomized trial included patients with cutaneous melanoma ≥ 1.0 mm Breslow thickness who underwent wide local excision and sentinel lymph node (SLN) biopsy. Univariate and multivariate analyses were performed to determine factors associated with TIL response, disease-free survival (DFS), and overall survival (OS). A total of 515 patients were included; TIL response was classified as “brisk” (n = 100; 19.4%) or “non-brisk” (n = 415; 80.6%). Patients in the nonbrisk TIL group were more likely to have tumor-positive SLN (17.6% vs 7%; P = 0.0087). On multivariate analysis, nonbrisk TIL response, increased tumor thickness, and ulceration were significant independent predictors of tumor-positive SLN. By Kaplan-Meier analysis, 5-year DFS rate was 91 per cent for those with a brisk TIL response compared with 86 per cent in the nonbrisk group ( P = 0.41). The 5-year OS rates were 95 per cent versus 84 per cent in the brisk versus nonbrisk TIL groups, respectively ( P = 0.0083). However, on multivariate analysis, TIL response was not a significant independent factor predicting DFS or OS. TIL response is a significant predictor of SLN metastasis but is not a major predictor of DFS or OS.

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

2021 ◽  
Vol 53 (5) ◽  
pp. 547-557
Author(s):  
Ya’nan Yang ◽  
Chenchen Wang ◽  
Congqi Dai ◽  
Xinyang Liu ◽  
Wenhua Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Positive Association ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Met Amplification ◽  
Amplification Rate ◽  
Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

Tumor-Infiltrating Lymphocytes Predict Sentinel Lymph Node Positivity in Patients With Cutaneous Melanoma

2007 ◽  
Vol 25 (7) ◽  
pp. 869-875 ◽  
Author(s):  
Rebecca C. Taylor ◽  
Ami Patel ◽  
Katherine S. Panageas ◽  
Klaus J. Busam ◽  
Mary S. Brady
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Breslow Thickness ◽  
Anatomic Site ◽  
Primary Cutaneous Melanoma ◽  
Male Sex ◽  
Infiltrating Lymphocytes

Purpose Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the influence of TILs on outcome remains controversial. Studies evaluating the prognostic significance of TILs were published before routine examination of draining lymph nodes by sentinel lymph node (SLN) biopsy, the most important predictor of survival in patients with melanoma. The prognostic implications of TILs were re-evaluated in a large group of patients undergoing SLN biopsy at our institution. Patients and Methods All patients who underwent SLN mapping for primary cutaneous melanoma between January 1996 and July 2005 were evaluated. Univariate and multivariate analyses were performed to assess factors that predict SLN positivity and survival. Factors analyzed included Breslow thickness, ulceration, anatomic site, sex, Clark level, age, mitotic rate, and the presence (brisk or nonbrisk) or absence of TIL. Results Eight hundred eighty-seven patients underwent SLN mapping, and a SLN was identified in 875 patients (98.8%). The SLN was positive for tumor in 156 patients (17.6%). Multivariate analysis revealed that only Breslow thickness (P < .0001), ulceration (P = .0004), male sex (P = .03), and absent TILs (P = .0003) were independently predictive of the presence of SLN metastases. In melanomas with a brisk TIL infiltrate, the probability of a positive SLN was 3.9% as compared with 26.2% for melanomas in which TILs were absent. TILs were not an independent predictive factor for survival. Conclusion The absence of TILs, together with increasing Breslow thickness, presence of ulceration and male sex, predicts SLN metastasis in patients undergoing SLN biopsy for primary cutaneous melanoma.

scholarly journals The prognostic significance and impact of the CXCR4-CXCR7-CXCL12 axis in primary cutaneous melanoma

2016 ◽  
Vol 175 (6) ◽  
pp. 1210-1220 ◽  
Author(s):  
A.T. McConnell ◽  
R. Ellis ◽  
B. Pathy ◽  
R. Plummer ◽  
P.E. Lovat ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
Primary Cutaneous Melanoma

scholarly journals Clinical characteristics and prognostic value of MEX3A mRNA in liver cancer

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8252 ◽  
Author(s):  
Dingquan Yang ◽  
Yan Jiao ◽  
Yanqing Li ◽  
Xuedong Fang
Keyword(s):  
Liver Cancer ◽  
Clinical Data ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Rna Seq ◽  
Diagnostic Ability ◽  
Kaplan Meier ◽  
Cox Analysis

Background MEX3A is an RNA-binding proteins (RBPs) that promotes the proliferation, invasion, migration and viability of cancer cells. The aim of this study was to explore the clinicopathological characteristics and prognostic significance of MEX3A mRNA expression in liver cancer. Methods RNA-Seq and clinical data were collected from The Cancer Genome Atlas (TCGA). Boxplots were used to represent discrete variables of MEX3A. Chi-square tests were used to analyze the correlation between clinical features and MEX3A expression. Receiver operating characteristic (ROC) curves were used to confirm diagnostic ability. Independent prognostic ability and values were assessed using Kaplan–Meier curves and Cox analysis. Results We acquired MEX3A RNA-Seq from 50 normal liver tissues and 373 liver cancer patients along with clinical data. We found that MEX3A was up-regulated in liver cancer which increased according to histological grade (p < 0.001). MEX3A showed moderate diagnostic ability for liver cancer (AUC = 0.837). Kaplan–Meier curves and Cox analysis revealed that the high expression of MEX3A was significantly associated with poor survival (OS and RFS) (p < 0.001). Moreover, MEX3A was identified as an independent prognostic factor of liver cancer (p < 0.001). Conclusions MEX3A expression shows promise as an independent predictor of liver cancer prognosis.

scholarly journals Relationship between Melanoma Stage at the Diagnosis and Survival During a period of 30 Years (1982-2011)

2018 ◽  
Vol 5 ◽  
Author(s):  
Talal M Alkhaldi ◽  
Sakhr A Dawari ◽  
Sami A Aldaham
Keyword(s):  
Cutaneous Melanoma ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Chi Square ◽  
Primary Cutaneous Melanoma ◽  
Kaplan Meier ◽  
Hispanic Patients ◽  
The U.S

Melanoma is a malignant tumor of melanocytes, and is a potentially aggressive cancer. The incidence of melanoma is rising at a greater rate than any other cancer in the U.S. The aim of this study was to examine the association between melanoma stage at the time of diagnosis and survival among U.S. adult melanoma patients during 1982-2011. This was a secondary analysis of a non-concurrent cohort study conducted on 185219 U.S. adult patients who were diagnosed with primary cutaneous melanoma between 1982-2011. Chi-square, Kaplan-Meier, and Cox proportional hazards regression were used to analyze the data. Significance was assessed using p-value and 95% confidence interval. Men had more cutaneous melanoma. Black non-Hispanic patients were diagnosed less frequently. Patients who were married or in a domestic partnership were most likely to be diagnosed. The adjusted HR for distant melanoma was 141-fold that of in situ (95% CI 126.38-157.19). The adjusted HR was the highest in the first decade of diagnosis (1.7; 95% CI 1.6 1.75). In conclusion, survival is highly affected by melanoma stage at diagnosis. Black non-Hispanic patients had the lowest hazard ratio of all races. The sample size was large, which enhances the generalizability to the U.S. population.

Prognostic significance of MAGE-A10 and NY-ESO-1 cancer-testis antigen in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21126-e21126
Author(s):  
Tanja Badovinac Crnjevic ◽  
Jasminka Jakic Razumovic ◽  
Giulio C Spagnoli ◽  
Paula Podolski ◽  
Nera Saric ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Curative Surgery ◽  
Kaplan Meier ◽  
Expression Score ◽  
Cancer Testis

e21126 Background: Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors. In normal adult tissues CTA expression is restricted predominantly to germs cells of the adult testis and placenta. Based on their tumor-restricted expression pattern, CTAs are regarded as valuable targets for cancer immunotherapy. The prognostic significance of CTAs in breast cancer has not been analyzed previously. Methods: To evaluate the potential prognostic significance of two member of this family, MAGE-A10 and NY-ESO-1 antigens, we examined their expression in breast cancer patients who underwent curative surgery at our hospital between 2002 and 2003. Paraffin embedded tumor sections were collected retrospectively from 165 breast cancer patients and immunohistochemical staining for MAGE-A10 and NY-ESO-1 was performed. Impact of MAGE-A10 and NY-ESO-1 expression on disease free survival (DFS) and overall survival (OS) was analyzed by the Kaplan-Meier method using 8-year follow up data. Results: MAGE-A10 expression (score ≥2+) was detected in 105/164 (64%) and NY-ESO-1 expression (score ≥2+) was observed in 14/164 (8.5%) patients. 8-year DFS for MAGE-A10 positive patients was 69% and 73% for MAGE-A10 negative (p=0.452). 8-year OS for MAGE-A10 positive patients was 80% and 90% for MAGE-A10 negative (p=0.134). For NY-ESO-1 positive patients 8-year DFS was 67% and 70% for NY-ESO-1 negative patients (p=0.837). 8-year OS for NY-ESO-1 positive patients was 83% and 84% for NY-ESO-1 negative patients. (p=0.991) Conclusions: To our knowledge this is the first study analyzing prognostic significance CTAs in breast cancer. In this retrospective study we did not show statistically significant correlation between MAGE-A10 and NY-ESO-1 expression and clinical outcome. Additional studies are warranted to determine weather this antigens might have prognostic value in breast cancer patients.

Concurrent deletion of BRCA2 and RB1 and aggressive prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 241-241
Author(s):  
Goutam Chakraborty ◽  
Joshua Armenia ◽  
Ying Zhang Mazzu ◽  
Gouri Nanjangud ◽  
Kalyani Chadalavada ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Free Survival ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Rapid Progression ◽  
Rna Seq ◽  
Castration Resistance ◽  
Null Cell ◽  
Enhanced Sensitivity

241 Background: Pathogenic variants of BRCA2 have been observed in a substantial subset of men with metastatic castration resistance prostate cancer (mCRPC). Prostate cancer (PC) patients with germline mutations of BRCA2 experience more rapid progression of their localized PC to mCRPC. This stands in contrast to other cancers where BRCA2 alterations do not appear to be associated with a worse prognosis. We identified homozygous and hemizygous deletions of BRCA2 in a subset of primary PC, which had been previously unrecognized. BRCA2 deletion in PC more frequently co-exists with RB1 deletion rather than alone. BRCA2-RB1 co-deletion in primary PC (TCGA and Taylor cohort) is associated with a shorter disease free survival and increased genomic instability in patients, indicating that BRCA2-RB1 null tumors are likely very aggressive in nature. Methods: To determine the underlying molecular and genomic consequences of BRCA2- RB1 loss, we CRISPR/shRNA-out these genes from human PC cell lines and subjected them to various in vitro assays, RNA-seq and kinase arrays. We applied a 3-color FISH assay to identify the deletion of BRCA2 and RB1 in PC. Results: BRCA2-RB1 null LNCaP cells exhibit androgen independence as evidenced by relative resistance to enzalutamide, and increased growth in absence of androgen but show enhanced sensitivity towards PARPi or platinum. Moreover, the null cell induces an aggressive EMT like phenotype, which is associated with enhanced migration and invasion. RNA-seq and array results show significant activation of EMT related signaling pathways including an unexpected activation of WNK1 upon co-deletion of BRCA2-RB1. FISH assay revealed significant co-deletion of BRCA2-RB1 in ADT resistant aggressive PC tumor cells. More importantly these cells also show greater sensitivity towards PARPi or platinum. Conclusions: Our finding suggests that concurrent deletion of BRCA2-RB1 is most likely is a driver of therapy resistant aggressive PC rather than the consequence of exposure to therapy. We propose that screening for BRCA2-RB1 deletion early could be implemented to identify those at highest risk of aggressive PC and provide an opportunity for early intervention and alternative treatments.

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