CD274 (PD-L1), CDKN2A (p16), TP53, and EGFR immunohistochemical profile in primary, recurrent and metastatic vulvar cancer

Lérias, Sofia; Esteves, Susana; Silva, Fernanda; Cunha, Mário; Cochicho, Daniela; Martins, Luciana; Félix, Ana

doi:10.1038/s41379-019-0429-z

Cited by 19 publications

(36 citation statements)

References 52 publications

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“…Additionally, a high FCER1G expression was observed more in the right side of the colon than in the left side of the colon. In addition, a previous study demonstrated a similar association of CD274 and CD3G considering lymph node metastases [ 27 ] and hypermutation [ 28 ], respectively.…”

Section: Resultsmentioning

confidence: 72%

The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer

et al. 2022

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The impact of germline variants on the regulation of the expression of tumor microenvironment (TME)-based immune response genes remains unclear. Expression quantitative trait loci (eQTL) provide insight into the effect of downstream target genes (eGenes) regulated by germline-associated variants (eVariants). Through eQTL analyses, we illustrated the relationships between germline eVariants, TME-based immune response eGenes, and clinical outcomes. In this study, both RNA sequencing data from primary tumor and germline whole-genome sequencing data were collected from patients with stage III colorectal cancer (CRC). Ninety-nine high-risk subjects were subjected to immune response gene expression analyses. Seventy-seven subjects remained for further analysis after quality control, of which twenty-two patients (28.5%) experienced tumor recurrence. We found that 65 eQTL, including 60 germline eVariants and 22 TME-based eGenes, impacted the survival of cancer patients. For the recurrence prediction model, 41 differentially expressed genes (DEGs) achieved the best area under the receiver operating characteristic curve of 0.93. In total, 19 survival-associated eGenes were identified among the DEGs. Most of these genes were related to the regulation of lymphocytes and cytokines. A high expression of HGF, CCR5, IL18, FCER1G, TDO2, IFITM2, and LAPTM5 was significantly associated with a poor prognosis. In addition, the FCER1G eGene was associated with tumor invasion, tumor nodal stage, and tumor site. The eVariants that regulate the TME-based expression of FCER1G, including rs2118867 and rs12124509, were determined to influence survival and chromatin binding preferences. We also demonstrated that FCER1G and co-expressed genes in TME were related to the aggregation of leukocytes via pathway analysis. By analyzing the eQTL from the cancer genome using germline variants and TME-based RNA sequencing, we identified the eQTL in immune response genes that impact colorectal cancer characteristics and survival.

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Section: Resultsmentioning

confidence: 72%

The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer

et al. 2022

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“…According to the literature, AEC2 and 3CL proteins serve as direct targets for blocking COVID-19 [1]. Meanwhile, the proteins of CFS2 and PTGS2 are associated with inflammation [45], and EGFR and TP53 regulate the immune response [46]. Based on the aforementioned molecular docking results, the scores of emodin with the key targets were all less than −5.0 kcal/mol, of which 6 targets had a score less than −7.0 kcal/mol.…”

Section: Results Of Molecular Dockingmentioning

confidence: 99%

Revealing the therapeutic targets and molecular mechanisms of emodin-treated coronavirus disease 2019 via a systematic study of network pharmacology

Zhu

Chen

et al. 2021

Aging

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Emodin has shown pharmacological effects in the treatment of infection with severe acute respiratory syndrome coronavirus-2, which leads to coronavirus disease 2019 (COVID-19). Thus, we speculated that emodin may possess anti-COVID-19 activity. In this study, using bioinformatics databases, we screened and harvested the candidate genes or targets of emodin and COVID-19 prior to the determination of pharmacological targets and molecular mechanisms of emodin against COVID-19. We discovered core targets for the treatment of COVID-19, including mitogen-activated protein kinase 1 (MAPK1), tumor protein (TP53), tumor necrosis factor (TNF), caspase-3 (CASP3), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), interleukin 1B (IL1B), mitogen-activated protein kinase 14 (MAPK14), prostaglandinendoperoxide synthase 2 (PTGS2), B-cell lymphoma-2-like protein 1 (BCL2L1), interleukin-8 (CXCL8), myeloid cell leukemia-1 (MCL1), and colony stimulating factor 2 (CSF2). The GO analysis of emodin against COVID-19 mainly included cytokine-mediated signaling pathway, response to lipopolysaccharide, response to molecule of bacterial origin, developmental process involved in reproduction, and reproductive structure development. The KEGG results exhibited that the molecular pathways mainly included IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, pertussis, proteoglycans in cancer, pathways in cancer, MAPK signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, etc. Also, molecular docking results revealed the docking capability between emodin and COVID-19 and the potential pharmacological activity of emodin against COVID-19. Taken together, these findings uncovered the targets and pharmacological mechanisms of emodin for treating COVID-19 and suggested that the vital targets might be used as biomarkers against COVID-19.

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“…GBF1 is required for the trans-Golgi network localization of HPV16 infection (35), which inactivates tumor suppressor protein p53 in penile carcinoma. It has been found that specific mutations or changes in expression of TP53 are correlated with LNM in various cutaneous squamous cell carcinomas (36)(37)(38), and alterations in TP53 were significantly associated with shorter event-free survival (10). In addition, higher prevalence in positive-node patients along with the tendency towards shorter survival were observed in PIK3CA and LAMC3 mutants.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between the Evolution of Somatic Alterations During Lymphatic Metastasis and Clinical Outcome in Penile Squamous Cell Carcinoma

et al. 2021

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Penile squamous cell carcinoma (PSCC) is a rare malignancy with poor survival after standard treatment. Although genomic alterations of PSCC have been characterized in several latest studies, the association between the formation of somatic landscape and regional lymph node metastasis (LNM), an important predictor for patient survival, has not been comprehensively investigated. Here, we collected formalin-fixed paraffin-embedded tumor tissue and matched normal samples of 32 PSCC patients, including 14 LNM patients and 18 clinically node-negative patients, to implement a whole-exome sequencing. Comparison of genomic features among different lymph node status subgroups was conducted after genomic profiling and its effects on patient survival were explored. Top-ranked recurrent gene mutants in our PSCC cohort were TP53 (13/32), NOTCH1 (12/32), CDKN2A (11/32), TTN (9/32) and FAT1 (8/32), mainly identified in the Notch, Hippo, cell cycle, TP53, RTK-RAS and PI3K pathways. While CDKN2A was confirmed to be the driver gene in all PSCC patients, certain gene mutants were significantly enriched in LNM involved patients, including TP53 (9/14 vs. 4/18, p = 0.029) and GBF1 (4/14 vs. 0/18, p = 0.028). Overall survival stratification of PSCC patients were found to be significantly correlated with mutations of three genes, including PIK3CA (Hazard ratio [HR] = 4.15, p = 0.029), CHD7 (HR = 4.82, p = 0.032) and LAMC3 (HR = 15.9, p < 0.001). PIK3CA and LAMC3 held a higher prevalence in patients with LNM compared to those without LNM (PIK3CA: 3/14 vs. 1/18, LAMC3: 2/14 vs. 1/18). Our finding demonstrated that genomic divergence exists across PSCC patients with different lymph node statuses, and it may be correlated with their survival outcome. It helps delineate somatic evolution during tumor progression and perfect potential therapeutic intervention in this disease.

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CD274 (PD-L1), CDKN2A (p16), TP53, and EGFR immunohistochemical profile in primary, recurrent and metastatic vulvar cancer

Cited by 19 publications

References 52 publications

The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer

The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer

Revealing the therapeutic targets and molecular mechanisms of emodin-treated coronavirus disease 2019 via a systematic study of network pharmacology

Correlation Between the Evolution of Somatic Alterations During Lymphatic Metastasis and Clinical Outcome in Penile Squamous Cell Carcinoma

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