The prognostic significance of infiltrating immune cells subtypes in invasive ductal carcinoma of the breast.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23177-e23177
Author(s):  
Qiuhong Zheng

e23177 Background: To explore the correlation between tumour infiltrating immune cell subsets and breast cancer prognosis. Methods: Specimens of 102 patients with invasive breast ductal carcinoma were analyzed for immune -related markers (CD8, CD20, FoxP3 and CD68). The number of positive cells in 3 most highly-stained intratumoural stroma areas of the primary tumour was counted. The mean number of each marker was calculated and used to divide patients into two groups respectively (CD8high/CD8low group, CD20high/CD20low group, FOXP3high/ FOXP3 low group and CD68high/CD68 low group). Results: Kaplan–Meier survival analysis showed : (A) For all patients, high tumour-infiltrating CD8+ and CD20+ B lymphocytes , low tumour-infiltrating FoxP3+ Treg and CD68+ macrophages all increased the OS and DFS (P < 0.05); (B) For both the 35 ER negative and the 45 lymphonode negative patients, high CD8+ CTLs increased the OS and DFS(P < 0.05). Multivariate analysis of OS and DFS showed for all patients, high CD8+ CTLs and low FoxP3+ Treg were related to good OS and DFS(P < 0.05). Conclusions: high number of tumour-infiltrating CD8 and low FoxP3 T lymphocytes both could function as potential independent prognostic markers for invasive ductal breast carcinoma .

2018 ◽  
Vol 104 (3) ◽  
pp. 196-201 ◽  
Author(s):  
Yangmei Xu ◽  
Suzhen Lan ◽  
Qiuhong Zheng

Purpose: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. Materials and methods: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low). Results: Kaplan-Meier survival analysis showed (a) for all patients that high tumor-infiltrating CD8+ and CD20+ B lymphocytes, low tumor-infiltrating FOXP3+ regulatory T cells (Tregs), and CD68+ macrophages all increased OS and DFS (p<0.05); (b) for both the 35 ER-negative and 45 lymph–node-negative patients, high CD8+ cytotoxic T lymphocytes (CTLs) increased OS and DFS (p<0.05). Multivariate analysis of OS and DFS showed that for all patients high CD8+ CTLs and low FOXP3+ Tregs were related to good OS and DFS (p<0.05). Conclusion: High numbers of tumor-infiltrating CD8+ and low numbers of FOXP3+ T lymphocytes both could function as potential independent prognostic markers for invasive ductal breast carcinoma.


2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.


2016 ◽  
Vol 19 (4) ◽  
pp. 351-357 ◽  
Author(s):  
Gabriel Chamel ◽  
Jérôme Abadie ◽  
Olivier Albaric ◽  
Sophie Labrut ◽  
Frédérique Ponce ◽  
...  

Objectives The aim of the study was to describe the clinical outcome of 30 cats with non-ocular melanomas and to evaluate the association between clinical or pathological parameters and overall survival time. Methods The database of the animal histopathological laboratory of the National Veterinary School of Nantes (Oniris, Nantes, France) was retrospectively searched to identify cases of feline non-ocular melanomas between December 2009 and April 2014. For each case, clinical data, including signalment, location of the primary tumour, staging, treatment and outcome, were collected from the medical records or via interviews with referring veterinarians. Histological and immunohistochemical evaluation included mitotic index, cytonuclear atypias, junctional activity, Melan A and S100 immunostaining, and surgical margins. Univariate analysis to test the prognostic value of the different variables was performed by the Kaplan–Meier product limit method using the log-rank test of significance. Results Thirty cats were included in the study. Eleven had a cutaneous non-auricular melanoma, six had a tumour located on the pinna and 13 had a tumour in the oral cavity. Cats with auricular melanomas were significantly younger than cats with tumours in other locations. Location and presence of clinical signs were not of prognostic significance, but the achromic phenotype was significantly associated with a poorer prognosis. Twenty cats were treated with surgery and survived significantly longer than cats that received only medical treatment or that did not receive any treatment. According to our data, mitotic index, cytonuclear atypias, junctional activity, Melan A or S100 expression, and surgical margins were not associated with survival. Conclusions and relevance We show for the first time, in a large series, that the auricular form of melanoma affected significantly younger cats than other extraocular forms. Most feline non-ocular melanomas are malignant and achromic tumours are associated with a poorer prognosis. According to this study, surgery should be considered as a priority.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Hui Lee ◽  
Jason Chia-Hsun Hsieh ◽  
Tyler Min-Hsien Wu ◽  
Ting-Shiuan Yeh ◽  
Hung-Ming Wang ◽  
...  

Abstract Background Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. Methods Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45– cells and cCSCs as CD133+EpCAM+Hoechst+CD45– cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. Results We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. Conclusions Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16256-e16256
Author(s):  
Xianghou Xia ◽  
Yang Yu ◽  
Hongjian Yang ◽  
Dehong Zou ◽  
Canming Wang ◽  
...  

e16256 Background: Although pyroptosis is critical for macrophages against pathogen infection, its role in cancer cells remains elusive. GSDMC is a pyroptosis executioner newly identified in cancer cells and have been shown to facilitate inflammatory tumor death. However, the expression of GSDMC in Pancreatic Ductal Adenocarcinoma (PDAC), its prognostic significance and possible impact on reshaping tumor immune microenviroment in PDAC is still unknown. Methods: We investigated the expression level of GSDMC using TNM plotter with TCGA and GTEx databases, the prognostic value of GSDMC in PDAC using Kaplan-Meier plotter with TCGA, GTEx and TCGA databases. The correlations between GSDMC and immune infiltration in PDAC were calculated using TIMER2.0 and TIDE with TCGA database. We further validated the prognostic value of GSDMC with immunohistochemistry(IHC) staining on a tissue microarray of 172 cases of PDAC patients receiving treatment in our institution. Correlations between expression of GSDMC and tumor infiltration lymphacytes(TILs) cells were also analyzed on tissue samples of those 172 PDAC patients. Results: TNM plotter analysis shows that the expression of GSDMC in PDAC tumor tissue is 10.49 folds higher than it is in pancreatic normal tissues (p = 8.86*e-56). Results from Kaplan-Meier plotter analysis shows high expression of GSDMC is significantly correlated with poorer overall survival(OS), HR = 1.8(1.19−2.71) logrank P = 0.004 and shorter relapse free survival (RFS), HR = 4.6(1.94−10.88), Logrank P = 0.00014 in PDAC. Analysis with TIMER2.0 and TIDE platform shows that expression of GSDMC is positively correlated with immunosuppressive cells, Cancer Associated Fiberblast (CAF) and Meyloid Derived Tumor Suprresso Cells(MDTSC). IHC staining analysis results is also consistent with aformentioned bioinformatic analysis, showing that high GSDMC expression correlated with shorter OS and reduced Tils infiltration. Conclusions: Our findings suggest that high expression of GSDMC is related to poor prognosis and compromised immune cell infiltration in PDAC. GSDMC holds promise for serving as a valuable prognostic marker and therapeutic target in PDAC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qian Chen ◽  
Bingqing Qiu ◽  
Xiaoyun Zeng ◽  
Lang Hu ◽  
Dongping Huang ◽  
...  

Abstract Background Previous studies have found that the microenvironment of cervical cancer (CESC) affects the progression and treatment of this disease. Thus, we constructed a multigene model to assess the survival of patients with cervical cancer. Methods We scored 307 CESC samples from The Cancer Genome Atlas (TCGA) and divided them into high and low matrix and immune scores using the ESTIMATE algorithm for differential gene analysis. Cervical cancer patients were randomly divided into a training group, testing group and combined group. The multigene signature prognostic model was constructed by Cox analyses. Multivariate Cox analysis was applied to evaluate the significance of the multigene signature for cervical cancer prognosis. Prognosis was assessed by Kaplan–Meier curves comparing the different groups, and the accuracy of the prognostic model was analyzed by receiver operating characteristic-area under the curve (ROC-AUC) analysis and calibration curve. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between the multigene signature and immune cell infiltration. Results We obtained 420 differentially expressed genes in the tumor microenvironment from 307 patients with cervical cancer. A three-gene signature (SLAMF1, CD27, SELL) model related to the tumor microenvironment was constructed to assess patient survival. Kaplan–Meier analysis showed that patients with high risk scores had a poor prognosis. The ROC-AUC value indicated that the model was an accurate predictor of cervical cancer prognosis. Multivariate cox analysis showed the three-gene signature to be an independent risk factor for the prognosis of cervical cancer. A nomogram combining the three-gene signature and clinical features was constructed, and calibration plots showed that the nomogram resulted in an accurate prognosis for patients. The three-gene signature was associated with T stage, M stage and degree of immune infiltration in patients with cervical cancer. Conclusions This research suggests that the developed three-gene signature may be applied as a biomarker to predict the prognosis of and personalized therapy for CESC.


2020 ◽  
Vol 21 (14) ◽  
pp. 5098 ◽  
Author(s):  
Jessica L. Bell ◽  
Sven Hagemann ◽  
Jessica K. Holien ◽  
Tao Liu ◽  
Zsuzsanna Nagy ◽  
...  

Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.


2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Zhicheng Liu ◽  
Dingquan Yang ◽  
Yanqing Li ◽  
Yan Jiao ◽  
Guangchao Lv

Abstract Background: The present study aimed to examine the diagnostic and prognostic value of HN1 in terms of overall survival (OS) and recurrence-free survival (RFS) in liver cancer and its potential regulatory signaling pathway. Methods: We obtained clinical data and HN1 RNA-seq expression data of liver cancer patients from The Cancer Genome Atlas database, and analyzed the differences and clinical association of HN1 expression in different clinical features. We uesd receiver-operating characteristic curve to evaluate the diagnosis capability of HN1. We analyzed and evaluated the prognostic significance of HN1 by Kaplan–Meier curves and Cox analysis. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways related to HN1 expression. Results: HN1 mRNA was up-regulated in liver cancer, and was associated with age, histologic grade, stage, T classification, M classification, and vital status. HN1 mRNA had ideal specificity and sensitivity for the diagnosis (AUC = 0.855). Besides, the analysis of Kaplan–Meier curves and Cox model showed that HN1 mRNA was strongly associated with the overall survival and could be well-predicted liver cancer prognosis, as an independent prognostic variable. GSEA analysis identified three signaling pathways that were enriched in the presence of high HN1 expression. Conclusion: HN1 serves as a biomarker of diagnosis and prognosis in liver cancer.


2021 ◽  
Author(s):  
Lijuan Jian ◽  
Min Zhang ◽  
Qi Wu ◽  
Xinping Min ◽  
Bowen Li ◽  
...  

Abstract Background: GLUT10 is encoded by SLC2A10 gene. Recent investigations have shown that GLUT10 is not only involved in glucose metabolism, but also involved in the body's immune response to cancer cells. However, the correlations between GLUT10 expression and prognosis, immune cells infiltrating of different cancers remain unclear.Methods: We Knocked down SLC2A10 and performed transcriptome sequencing to analyze the biological function of GLUT10. The SLC2A10 expression level was analyzed by the Oncomine databases and Tumor immune Estimation Resource (TIMER) site. We evaluated the prognostic potential of SLC2A10 in different cancers using the Kaplan-Meier plotter database and the PrognoScan online software. The correlations between SLC2A10 expression and immune infiltrates were analyzed by TIMER. In addition, correlations between SLC2A10 expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.Results: Knocking down of SLC2A10 widely activated immune and inflammatory signaling. SLC2A10 was abnormally expressed in several tumors. The expression level of SLC2A10 was closely correlated with cancer prognosis. Low SLC2A10 expression was related to poorer prognosis and increased malignancy of lung cancer. Lung cancer patients with low expression of SLC2A10 have a much shorter median survival time than patients with high expression of SLC2A10. SLC2A10 expression is closely related to different types of immune cell infiltration, particularly with macrophages.Conclusions: By using various databases and analysis software, we found that GLUT10 is involved in tumor immunity and is expected to serve as a therapeutic target in the future. Down-regulation of SLC2A10 expression predicts poor prognosis of lung cancer. GLUT10 may be a new important immune regulating molecular thus worth further focusing.


2020 ◽  
Author(s):  
Yali Wang ◽  
Kun Zheng ◽  
Xiuqiong Chen ◽  
Rui Chen ◽  
Yanmei Zou

Background This study aimed to use bioinformatics tools to explore pivotal genes associated with the occurrence of gastric cancer (GC) and assess their prognostic significance, and link with clinicopathological parameters. We also investigated the predictive role of COL1A1, THBS2, and SPP1 in immunotherapy. Materials and methods We identified differential genes (DEGs) that were up- and down-regulated in the three datasets (GSE26942, GSE13911, and GSE118916) and created protein-protein interaction (PPI) networks from the overlapping DEGs. We then investigated the potential functions of the hub genes in cancer prognosis using PPI networks, and explored the influence of such genes in the immune environment. Results Overall, 268 overlapping DEGs were identified, of which 230 were up-regulated and 38 were down-regulated. CytoHubba selected the top ten hub genes, which included SPP1, TIMP1, SERPINE1, MMP3, COL1A1, BGN, THBS2, CDH2, CXCL8, and THY1. With the exception of SPP1, survival analysis using the Kaplan-Meier database showed that the levels of expression of these genes were associated with overall survival. Genes in the most dominant module explored by MCODE, COL1A1, THBS2, and SPP1, were primarily enriched for two KEGG pathways. Further analysis showed that all three genes could influence clinicopathological parameters and immune microenvironment, and there was a significant correlation between COL1A1, THBS2, SPP1, and PD-L1 expression, thus indicating a potential predictive role for GC response to immunotherapy. Conclusion ECM-receptor interactions and focal adhesion pathways are of great significance in the progression of GC. COL1A1, THBS2 and SPP1 may help predict immunotherapy response in GC patients.


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