scholarly journals E-Cadherin, Integrin Alpha2 (Cd49b), and Transferrin Receptor-1 (Tfr1) Are Promising Immunohistochemical Markers of Selected Adverse Pathological Features in Patients Treated with Radical Prostatectomy

2021 ◽  
Vol 10 (23) ◽  
pp. 5587
Author(s):  
Piotr Zapała ◽  
Łukasz Fus ◽  
Zbigniew Lewandowski ◽  
Karolina Garbas ◽  
Łukasz Zapała ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Locally Advanced ◽  
The Cancer Genome Atlas ◽  
Nerve Sparing ◽  
Immunohistochemical Markers ◽  
Transferrin Receptor 1 ◽  
Pathologic Features ◽  
High Discrimination ◽  
Cancer Genome Atlas ◽  
E Cadherin

In patients treated for prostate cancer (PCa) with radical prostatectomy (RP), determining the risk of extraprostatic extension (EPE) and nodal involvement (NI) remains crucial for planning nerve-sparing and extended lymphadenectomy. The study aimed to determine proteins that could serve as immunohistochemical markers of locally advanced PCa. To select candidate proteins associated with adverse pathologic features (APF) reverse-phase protein array data of 498 patients was retrieved from The Cancer Genome Atlas. The analysis yielded 6 proteins which were then validated as predictors of APF utilizing immunohistochemistry in a randomly selected retrospective cohort of 53 patients. For univariate and multivariate analysis, logistic regression was used. Positive expression of TfR1 (OR 13.74; p = 0.015), reduced expression of CD49b (OR 10.15; p = 0.013), and PSA (OR 1.29; p = 0.013) constituted independent predictors of EPE, whereas reduced expression of e-cadherin (OR 10.22; p = 0.005), reduced expression of CD49b (OR 24.44; p = 0.017), and PSA (OR 1.18; p = 0.002) were independently associated with NI. Both models achieved high discrimination (AUROC 0.879 and 0.888, respectively). Immunohistochemistry constitutes a straightforward tool that might be easily utilized before RP. Expression of TfR1 and CD49b is associated with EPE, whereas expression of e-cadherin and CD49b is associated with NI. Since following immunohistochemical markers predicts respective APFs independently from PSA, in the future they might supplement existing preoperative nomograms or be implemented in novel tools.

scholarly journals Downstream Neighbor of SON (DONSON) Expression Is Enhanced in Phenotypically Aggressive Prostate Cancers

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3439 ◽  
Author(s):  
Niklas Klümper ◽  
Marthe von Danwitz ◽  
Johannes Stein ◽  
Doris Schmidt ◽  
Anja Schmidt ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Locally Advanced ◽  
Metastatic Potential ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Prostate Cancers ◽  
Migration Capacity

Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods: DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.

scholarly journals Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jean Paul Nshizirungu ◽  
Sanae Bennis ◽  
Ihsane Mellouki ◽  
Mohammed Sekal ◽  
Dafr-Allah Benajah ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Research ◽  
Overall Survival ◽  
Molecular Subtypes ◽  
Clinicopathological Features ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Gastric Cancer Patients ◽  
Genome Atlas ◽  
E Cadherin

Introduction. The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. Methods. Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). Results. Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.

The impact of race on adverse pathologic features at the time of radical prostatectomy in men with prostate cancer and implications for adjuvant radiotherapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 75-75
Author(s):  
Gregory Arthur Jordan ◽  
Richa Bhasin ◽  
Alec Block ◽  
Alex Gorbonos ◽  
Marcus Lee Quek ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Black Men ◽  
Adjuvant Radiotherapy ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Positive Margins ◽  
Advanced Tumor ◽  
Pathologic Features ◽  
The Impact

75 Background: Patients with adverse pathologic features (≥pT3 disease or positive margins) at the time of radical prostatectomy (RP) have higher biochemical recurrence (BR). Adjuvant radiotherapy (ART) reduces BR, but has potential toxicities. Also, studies suggest Black men are more likely to have aggressive prostate cancer. Our objective was to identify whether black men undergoing RP are more likely to have adverse pathologic features (APF) that lead to an indication for ART. Methods: We conducted a retrospective cohort study of men with cT1-4 Nx/0 Mx/0 prostate adenocarcinoma in the National Cancer Database who underwent RP. Race was divided into 3 groups (Caucasian, Black, Other). Chi-square tests and analysis of variance (ANOVA) tests were used to compare clinical and socioeconomic covariates between race groups. Univariate (UVA) and multivariable analysis (MVA) were performed using logistic regression (LR) to identify covariates predicting for APF. LR was performed to identify the impact of race on pT3 disease and positive margins. Results: A total of 313,013 patients diagnosed between 2004-2014 and undergoing RP were included. 256,315 (85%) were Caucasian, 33,725 (11%) were Black, and 12,973 (4%) were Other race. Fewer Black men had Gleason group 1 (33% vs. 41%) but more had Gleason group 2 disease (46% vs. 38%, p < 0.001). Black men more frequently had PSA ≥10 ng/ml (18% vs. 16%, p < 0.001) and ≥cT2b disease (18% vs. 14%, p < 0.001). On UVA, Black men were more likely to have APF (Odds Ratio [OR] 1.18; 95% Confidence Interval [CI] 1.15-1.21; [p < 0.001]). On MVA, black race was independently associated with having APF (OR 1.21; 95% CI 1.18-1.24; p < 0.001). Black men were more likely to have positive margins (OR 1.26; 95% CI 1.22-1.29; p < 0.001) but less likely to have ≥pT3 disease (OR 0.77; 95% CI 0.74-0.79; p < 0.001). Conclusions: Independent of socioeconomic and clinical factors, Black men undergoing RP are more likely to have APF, increasing the risk of BR in this group, and more frequently creating an indication for ART. This appears to be more due to positive margins than locally advanced tumor. The underlying cause of this disparity warrants further exploration.

scholarly journals Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Lecai Xiong ◽  
Xiao Zhou ◽  
Yi Cai ◽  
Peng Dai ◽  
Jinping Zhao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Locally Advanced ◽  
Gene Signature ◽  
Treg Cells ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Prognostic Models ◽  
Competing Endogenous Rnas ◽  
Cancer Genome Atlas

Abstract Background: Lung adenocarcinoma (LUAD) is the most common form of non-small-cell lung cancer (NSCLC). Hypoxia has been found in 50 – 60% of locally advanced solid tumors and shown to be associated with poor prognosis in a variety of tumors, including NSCLC. The study focused on the hypoxia associated molecular hallmarks in LUAD.Methods: 15 hypoxia related genes were selected to define the hypoxia status of LUAD by ConsensusClusterPlus based on the data from The Cancer Genome Atlas(TCGA). Then, we investigate the immune status under different hypoxia status. Subsequently, we constructed prognostic models based on hypoxic-related differentially expressed genes (DEGs), identified hypoxia-related microRNAs, lncRNAs and mRNAs, and built a network based on the competing endogenous RNAs (ceRNAs) theory.Results: Two clusters (cluster1 and cluster2) were identified with different hypoxia status, cluster 1 was defined as the hypoxia subgroup, in which all 15 hypoxia-associated genes were upregulated. The infiltration of CD4 + T cells and Tfh cells was lower, while the infiltration of regulatory T (Treg) cells, the expression of PD-1/PD-L1 and TMB were higher in cluster 1, which indicated immunosuppressive status. Based on the DEGs, a risk signature containing 7 genes was established. Furthermore, three differentially expressed microRNAs (hsa-miR-9, hsa-miR-31, hsa-miR-196b) associated prognostic under different hypoxia clusters and its related mRNAs, lncRNAs were identified, then built a ceRNAs network.Conclusion: This study showed that hypoxia was associated with poor prognosis in LUAD and explored the potential mechanism from the perspective of gene signature and ceRNA theory.

scholarly journals Gene Expression Changes and Associated Pathways Involved in the Progression of Prostate Cancer Advanced Stages

2021 ◽  
Vol 11 ◽  
Author(s):  
Elena A. Pudova ◽  
George S. Krasnov ◽  
Anastasiya A. Kobelyatskaya ◽  
Maria V. Savvateeva ◽  
Maria S. Fedorova ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Markers ◽  
Interaction Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Bioinformatic Analysis ◽  
Early Recurrence ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Positive Correlations

Prostate cancer (PC) is one of the most common cancers among men worldwide, and advanced PCs, such as locally advanced PC (LAPC) and castration-resistant PC (CRPC), present the greatest challenges in clinical management. Current indicators have limited capacity to predict the disease course; therefore, better prognostic markers are greatly needed. In this study, we performed a bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets, including RNA-Seq data from the prostate adenocarcinoma (PRAD; n = 55) and West Coast Dream Team – metastatic CRPC (WCDT-MCRPC; n = 84) projects, to evaluate the transcriptome changes associated with progression-free survival (PFS) for LAPC and CRPC, respectively. We identified the genes whose expression was positively/negatively correlated with PFS. In LAPC, the genes with the most significant negative correlations were ZC2HC1A, SQLE, and KIF11, and the genes with the most significant positive correlations were SOD3, LRRC26, MIR22HG, MEG3, and MIR29B2CHG. In CRPC, the most significant positive correlations were found for BET1, CTAGE5, IFNGR1, and GIMAP6, and the most significant negative correlations were found for CLPB, PRPF19, ZNF610, MPST, and LINC02001. In addition, we performed a gene network interaction analysis using STRINGdb, which revealed a significant relationship between genes predominantly involved in the cell cycle and characterized by upregulated expression in early recurrence. Based on the results, we propose several genes that can be used as potential prognostic markers.

scholarly journals Clusterization in head and neck squamous carcinomas based on lncRNA expression: molecular and clinical correlates

2017 ◽  
Author(s):  
Pelayo G. de Lena ◽  
Abel Paz-Gallardo ◽  
Jesús M. Paramio ◽  
Ramón García-Escudero
Keyword(s):  
Head And Neck ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Anatomical Location ◽  
Sequencing Technologies ◽  
Papillomavirus Infection ◽  
Pathologic Features ◽  
Genetic Features ◽  
Cancer Genome Atlas ◽  
Cancer Types

AbstractBackgroundLong non-coding RNAs (lncRNAs) have emerged as key players in a remarkably variety of biological processes and pathologic conditions, including cancer. Next-generation sequencing technologies and bioinformatics procedures predict the existence of tens of thousands of lncRNAs, from which we know the functions of only a handful of them, and very little is known in cancer types such as head and neck squamous cell carcinomas (HNSCCs).ResultsHere, we use RNA-seq expression data from The Cancer Genome Atlas (TCGA) and various statistic and software tools in order to get insight about the lncRNome in HNSCC. Based on lncRNAs expression across 426 samples, we discover five distinct tumor clusters that we compare with reported clusters based on various genomic/genetic features. Results demonstrate significant associations between lncRNA-based clustering and DNA-methylation, TP53 mutation, and human papillomavirus infection. Using “guilt by association” procedures, we infer the possible biological functions of representative lncRNAs of each cluster. Furthermore, we found that lncRNA clustering is correlated with some important clinical and pathologic features, including patient survival after treatment, tumor grade or sub-anatomical location.ConclusionsWe present a landscape of lncRNAs in HNSCC, and provide associations with important genotypic and phenotypic features that may help to understand the disease.

Evaluation of preoperative prostate magnetic resonance imaging for cancer control and neurovascular tissue preservation during robotic radical prostatectomy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 101-101
Author(s):  
Samuel A Gold ◽  
Amir H Lebastchi ◽  
Jonathan Bloom ◽  
Sherif Mehralivand ◽  
Patrick H Gomella ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Radical Prostatectomy ◽  
Multivariable Analysis ◽  
Surgical Margin ◽  
Nerve Sparing ◽  
Positive Surgical Margin ◽  
Resonance Imaging ◽  
Pathologic Features ◽  
Neurovascular Bundles

101 Background: Prostate multi-parametric magnetic resonance imaging (mpMRI) can precisely depict prostate cancer (PCa) location and adverse pathologic features. Surgeons can utilize this information to maximize sparing of the neurovascular bundles (NVBs) during radical prostatectomy (RP) while avoiding a positive surgical margin (PSM). We detail the technique of using preoperative mpMRI to quantify its effect regarding nerve-sparing and rates of PSMs. Methods: A prospectively maintained database was queried for robotic-assisted RPs (RARPs) with preoperative mpMRI between 2007-2017. Imaging margin risk factors (iMRF) were defined on mpMRI as frank extraprostatic extension (EPE), possible EPE, and capsular irregularity (capsular bulge, lesion-capsule contact, or lesion adjacency to the neurovascular bundles). Surgical adjustments to nerve-sparing technique (full sparing, partial sparing, and wide excision) were made based on these findings. Results: Five hundred thirty-two patients comprising 1041 prostate sides were included for analysis. Overall, PSM rate was found in 80/1041 (7.7%) sides of the prostate. iMRF were seen in 313/1041 (30.1%) prostate sides, for which adjustments were made in 244/313 (78.0%) of these. In the 69/244 (22.0%) cases where full nerve-sparing was performed despite iMRF, PSM rate was 20/69 (29%) compared to 33/244 (13.5%), p = 0.002. MRI-guided surgical adjustments decreased PSM risk by 68% and 15% in pT3 and pT2 cases, respectively. On multivariable analysis, logPSA (odds ratio [OR] 4.06, [95% CI 2.40-12.3], p < 0.001) and iMRF (OR 1.78, [95% CI 1.01-3.16], p = 0.047) were significantly associated with PSM while nerve-sparing adjustment was significantly associated with decreased risk of PSM (OR 0.38 [95% CI 0.22-0.66], p = 0.001). Conclusions: MRI effectively detects risks for PSM and guides surgical adjustments to decrease PSM rates. As prostate MRI is more frequently acquired for PCa screening and biopsy, we show its additional value for RP planning and potentially improved outcomes.

scholarly journals The Landscape of Whole-genome Alterations and Pathologic Features in Genitourinary Malignancies: An Analysis of the Cancer Genome Atlas

2017 ◽  
Vol 3 (6) ◽  
pp. 584-589 ◽  
Author(s):  
Mark W. Ball ◽  
Michael A. Gorin ◽  
Charles G. Drake ◽  
Hans J. Hammers ◽  
Mohamad E. Allaf
Keyword(s):  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Whole Genome ◽  
Pathologic Features ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Combination of Radiosensitivity Gene Signature and PD-L1 Status Predicts Clinical Outcome of Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma: A Study Based on The Cancer Genome Atlas Dataset

2021 ◽  
Vol 8 ◽  
Author(s):  
Dongjun Dai ◽  
Yinglu Guo ◽  
Yongjie Shui ◽  
Jinfan Li ◽  
Biao Jiang ◽  
...  
Keyword(s):  
Risk Score ◽  
Cox Model ◽  
Trichostatin A ◽  
Locally Advanced ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
High Group ◽  
Cancer Genome Atlas ◽  
Score Model ◽  
Genome Atlas

Aim: The aim of our study was to investigate the potential predictive value of the combination of radiosensitivity gene signature and PD-L1 expression for the prognosis of locally advanced head and neck squamous cell carcinoma (HNSCC).Methods: The cohort was selected from The Cancer Genome Atlas (TCGA) and classified into the radiosensitive (RS) group and radioresistant (RR) group by a radiosensitivity-related gene signature. The cohort was also grouped as PD-L1-high or PD-L1-low based on PD-L1 mRNA expression. The least absolute shrinkage and selection operator (lasso)-based Cox model was used to select hub survival genes. An independent validation cohort was obtained from the Gene Expression Omnibus (GEO) database.Results: We selected 288 locally advanced HNSCC patients from TCGA. The Kaplan–Meier method found that the RR and PD-L1-high group had a worse survival than others (p = 0.033). The differentially expressed gene (DEG) analysis identified 553 upregulated genes and 486 downregulated genes (p &lt; 0.05, fold change &gt;2) between the RR and PD-L1-high group and others. The univariate Cox analysis of each DEG and subsequent lasso-based Cox model revealed five hub survival genes (POU4F1, IL34, HLF, CBS, and RNF165). A further hub survival gene-based risk score model was constructed, which was validated by an external cohort. We observed that a higher risk score predicted a worse prognosis (p = 0.0013). The area under the receiver operating characteristic curve (AUC) plots showed that this risk score model had good prediction value (1-year AUC = 0.684, 2-year AUC = 0.702, and 3-year AUC = 0.688). Five different deconvolution methods all showed that the B cells were lower in the RR and PD-L1-high group (p &lt; 0.05). Finally, connectivity mapping analysis showed that the histone deacetylase (HDAC) inhibitor trichostatin A might have the potential to reverse the phenotype of RR and PD-L1-high in locally advanced HNSCC (p &lt; 0.05, false discovery rate &lt;0.1).Conclusion: The combination of 31-gene signature and the PD-L1 mRNA expression had a potential predictive value for the prognosis of locally advanced HNSCC who had RT. The B cells were lower in the RR and PD-L1-high group. The identified risk gene signature of locally advanced HNSCC and the potential therapeutic drug trichostatin A for the RR and PD-L1-high group are worth being further studied in a prospective homogenous cohort.

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