scholarly journals Decreased Expression of PACSIN1 in Brain Glioma Samples Predicts Poor Prognosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhou Zimu ◽  
Zhang Jia ◽  
Fu Xian ◽  
Ma Rui ◽  
Ren Yuting ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Poor Prognosis ◽  
Molecular Subtype ◽  
Neurological Diseases ◽  
Postoperative Radiotherapy ◽  
Clinical Indicators ◽  
Kinase Substrate ◽  
Functional Annotations ◽  
Tissue Specimens ◽  
Brain Gliomas

Gliomas are the most severe brain tumours with a poor prognosis. Although surgery, postoperative radiotherapy and chemotherapy can improve the survival rate of glioma patients, the prognosis of most glioma patients is still poor. In recent years, the influence of gene-targeted therapy on gliomas has been gradually discovered, and intervening the occurrence and development of brain gliomas from the perspective of the gene will significantly improve treatment prognosis. Protein Kinase C and Casein Kinase Substrate in Neurons 1 (PACSIN1) is a member of the conserved peripheral membrane protein family in eukaryotes. Improper expression of PACSIN1 can lead to neurological diseases such as Huntington’s disease and schizophrenia. However, its relationship with tumours or even gliomas has not been explored. The study aims to explore PACSIN1 as a prognostic factor that can predict overall survival (OS) for gliomas. We collected the data from CGGA, TCGA, GEO databases and the pathological glioma tissue specimens from 15 clinical glioma patients surgically resected. The differential expression of PACSIN1 in various clinical indicators, the genes related to PACSIN1 expression, the prognostic value of PACSIN1 and the functional annotations and pathway analysis of differently expressed genes (DEGs) were analysed. The results revealed that PACSIN1 had low expression levels in grade IV, IDH1 wild-type and 1p/19q non-codel group gliomas, and PACSIN1 was considered a mesenchymal molecular subtype marker. PACSIN1 expression is positively correlated with OS in all gliomas and it was found that PACSIN1 influenced the occurrence and development of gliomas through synaptic transmission. The PACSIN1 expression is negatively correlated with the malignant degree of gliomas and positively associated with the OS, indicating that PACSIN1 would play an essential role in the occurrence and development of gliomas and might be a potential new biomarker and targeted therapy site for gliomas.

Co-expression of VEGF-B and FLT-1 correlates with malignancy and prognosis of gastric cancer

2021 ◽  
Author(s):  
Yanpeng Ma ◽  
Wenyao Wang ◽  
Longlong Liu ◽  
Yang liu ◽  
Wei Bi
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Targeted Therapy ◽  
Correlation Analysis ◽  
Detailed Analysis ◽  
Poor Prognosis ◽  
Rank Correlation ◽  
Spearman’S Rank Correlation

Background: This study aims to investigate the correlation of VEGF-B and FLT-1 co-expression with the prognosis of gastric cancer (GC). Materials & methods: Primary GC samples and adjacent tissues were obtained from 96 patients. Results: Both VEGF-B and FLT-1 were testified to be upregulated in the human GC compared with adjacent tissues. Spearman’s rank correlation analysis indicated that VEGF-B and FLT-1 expression were correlated (r = 0.321, p = 0.0015). High VEGF-B and FLT-1 co-expression patients showed poor prognosis when compared with low VEGF-B and FLT-1 co-expression patients (p = 0.0169). Conclusion: The high co-expression of VEGF-B and FLT-1 in GC shows a poor prognosis of overall survival, and targeted therapy against the interaction between VEGF-B and FLT-1 is worth further detailed analysis.

scholarly journals Postoperative Radiotherapy in Head and Neck Cancer

2010 ◽  
Vol 2 (1) ◽  
pp. 43-51
Author(s):  
Vedang Murthy ◽  
Sayan Kundu ◽  
Tanweer Shahid ◽  
Ashwini Budrukkar ◽  
Tejpal Gupta ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Targeted Therapy ◽  
Head And Neck ◽  
Neck Cancer ◽  
Early Stage ◽  
Postoperative Radiotherapy ◽  
Locally Advanced ◽  
Head And Neck Cancers ◽  
Advanced Head ◽  
Locoregional Failure

Abstract Though early stage head and neck cancers can be cured either by surgery or radiation, patients with locally advanced disease continues to pose a therapeutic challenge. Locoregional failure is the major cause of death in head and neck cancers. As the outcome of locally advanced head and neck cancer is less than promising, a combined modality approach is generally undertaken in this group of patients. The combination of surgery, radiation and more recently, chemotherapy and targeted therapy can improve outcomes in locally advanced head and neck cancer patients. This overview discusses the rationale and role of postoperative radiotherapy (PORT) in advanced head and neck cancers, the radiotherapy technique in brief and methods of enhancing the efficacy of postoperative RT by altering the fractionation schedules and adding chemotherapy and targeted therapy.

scholarly journals Decoding Clinical Biomarker Space of COVID-19: Exploring Matrix Factorization-based Feature Selection Methods

2021 ◽  
Author(s):  
Farshad Saberi-Movahed ◽  
Mahyar Mohammadifard ◽  
Adel Mehrpooya ◽  
Mohammad Rezaei-Ravari ◽  
Kamal Berahmand ◽  
...  
Keyword(s):  
Feature Selection ◽  
Poor Prognosis ◽  
Clinical Decision Making ◽  
Unmet Need ◽  
Clinical Decision ◽  
Clinical Indicators ◽  
Arterial Blood Gas ◽  
Clinical Biomarkers ◽  
Arterial Blood ◽  
Global Pandemic

One of the most critical challenges in managing complex diseases like COVID-19 is to establish an intelligent triage system that can optimize the clinical decision-making at the time of a global pandemic. The clinical presentation and patients' characteristics are usually utilized to identify those patients who need more critical care. However, the clinical evidence shows an unmet need to determine more accurate and optimal clinical biomarkers to triage patients under a condition like the COVID-19 crisis. Here we have presented a machine learning approach to find a group of clinical indicators from the blood tests of a set of COVID-19 patients that are predictive of poor prognosis and morbidity. Our approach consists of two interconnected schemes: Feature Selection and Prognosis Classification. The former is based on different Ma- trix Factorization (MF)-based methods, and the latter is performed using Random Forest algorithm. Our model reveals that Arterial Blood Gas (ABG) O2 Saturation and C-Reactive Protein (CRP) are the most important clinical biomarkers determining the poor prognosis in these patients. Our approach paves the path of building quantitative and optimized clinical management systems for COVID-19 and similar diseases.

Cancer-associated fibroblasts of colorectal cancer and their markers: updates, challenges and translational outlook

2020 ◽  
Vol 16 (29) ◽  
pp. 2329-2344 ◽  
Author(s):  
Marahaini Musa ◽  
Adli Ali
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Poor Prognosis ◽  
Mortality Rates ◽  
Colorectal Carcinogenesis ◽  
Detection Methods ◽  
Cancer Associated Fibroblasts ◽  
Marker Detection ◽  
Efficient Screening ◽  
Marker Identification

Accumulation of cancer-associated fibroblasts (CAFs) in the tumor microenvironment is associated with poor prognosis and recurrence of colorectal cancer (CRC). Despite their prominent roles in colorectal carcinogenesis, there is a lack of robust and specific markers to classify the heterogeneous and highly complex CAF populations. This has resulted in confusing and misleading definitions of CAFs in cancer niche. Advancements in molecular biology approaches have open doors to reliable CAF marker detection methods in various solid tumors. These discoveries would contribute to more efficient screening, monitoring and targeted therapy of CRC thus potentially will reduce cancer morbidity and mortality rates. This review highlights current scenarios, dilemma, translational potentials of CAF biomarker and future therapeutic applications involving CAF marker identification in CRC.

CD30 Immunohistochemical Expression In Diffuse Large B-Cell Lymphoma Is Associated With Decreased Overall Survival and The Non-Germinal Center Molecular Subtype

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4318-4318 ◽  
Author(s):  
Angela M. B. Collie ◽  
Brian T. Hill ◽  
Elena A. Manilich ◽  
Mitchell R Smith ◽  
Eric D. Hsi
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Poor Prognosis ◽  
De Novo ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Immunohistochemical Expression ◽  
Large B Cell Lymphoma

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity with multiple potential prognostic biomarkers. Cell of origin (COO) molecular subtype classification using gene expression profiling with microarrays and immunohistochemical expression of CD30 have been examined as potential prognostic markers, often with conflicting results. A recent study demonstrated that patients with CD30-positive DLBCL had better prognosis compared to patients with CD30-negative DLBCL and had a distinct gene expression profile (Hu S et al. Blood. 121(14): 2715-24, 2013). In addition, due to the development of targeted therapies such as an anti-CD30 monoclonal antibody drug conjugate, the identification and prognostic relevance of this biomarker has potential therapeutic impact. We evaluated CD30 expression, determined by immunohistochemistry, in a cohort of de novo DLBCL cases at our institution and examined cell of origin molecular subtype in the CD30-positive and CD30-negative groups. Design 94 adult patients with de novo DLBCL uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) as first line therapy were identified at The Cleveland Clinic. Clinical data was collected for these patients. A tissue microarray was created and stained with antibodies to CD10, CD20, CD30, BCL-6, and MUM-1. COO subtype was determined for the Hans algorithm in all cases. CD30 was considered positive when expression was seen in ≥ 20% of tumor cells. Results There were no significant differences in sex, age, IPI score, or stage between patients in the CD30-positive and CD30-negative groups. The median age of the DLBCL cohort was 63 years (range 17-91 years) with a male : female ratio of 1:1.1. 54% of patients had stage III or IV disease. Median follow-up was 58 months. 9 of 94 DLBCL samples (9.6%) were positive for CD30 by immunohistochemistry. By Kaplan-Meier analysis, the CD30-positive cases showed a decreased overall survival compared to the CD30-negative cases (Figure 1, p=0.044). Multivariate analysis using a Cox proportional hazard model confirmed that CD30 expression was independent of IPI and a significant factor for overall survival (hazard ratio = 3.05; 95% confidence interval = 1.12-8.30; p = 0.0291). All 9 of the CD30-positive DLBCL samples were of the non-germinal center B-cell-like (NGC) subtype using the Hans immunohistochemical algorithm, which was significantly more than the CD30-negative samples (42/85) (p = 0.003). Conclusion CD30 expression was associated with poor prognosis in our cohort, in contrast to recent studies. However, CD30 expression was highly associated with the NGC subtype of DLBCL and might contribute to the pathogenesis of these lymphomas through NF-κB activation. Given the poor prognosis of NGC DLBCLs, targeting CD30 in DLBCL should be explored. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Metastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor

2011 ◽  
Vol 68 (4) ◽  
pp. 359-362 ◽  
Author(s):  
Daniela Kolarevic ◽  
Zorica Tomasevic ◽  
Ivan Boricic ◽  
Dejan Rasic ◽  
Natasa Andjelic-Dekic ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Lymph Nodes ◽  
Maxillary Sinus ◽  
Poor Prognosis ◽  
Postoperative Radiotherapy ◽  
Extrahepatic Metastasis ◽  
Histopathological Analysis ◽  
Dental Surgery ◽  
Tumor Mass ◽  
The Right

Introduction. Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of the liver. It is usually seen in the 6th and 7th decades of life and chronic hepatitis B is the most frequent cause. Extrahepatic metastasis of HCC is an indicator of a poor prognosis and the most common sites are lungs, bones, lymph nodes, kidneys and adrenal glands. We reported a case of isolated metastasis in the right maxilla, which had been found initially, before the tumor in the liver was diagnosed. Case report. A 70-year-old man underwent dental surgery of the upper right molar. Prolonged bleeding control was difficult for up to two weeks, so the biopsy was performed. Histopathological analysis revealed a metastatic hepatocellular carcinoma. Computerized tomography (CT) of the abdomen revealed a diffusely heterogeneous liver parenchyma with irregular borders and two foci of mass lesions. There were metastasis in the spleen and also two pathological retroperitoneal lymph nodes were detected, but no ascit, liver cirrhosis, cholestasis or portal vein thrombosis were seen. CT of the orbital and maxillary regions revealed a tumor mass in the right maxillary sinus, spreading to the alveolar sinus, nasal cavity and partially infratemporal space. A tumor mass was in the right orbit as well, infiltrating the surrounding bones and muscles. Clinically, there was proptosis of the right eye accompanied by amaurosis. The treatment started with chemotherapy based on 5-fluorouracil (sorafenib was not available). After three cycles, control CTs showed a stable disease in the liver, but progression in the right maxillary sinus and orbit. Enucleation of the right eye was performed and postoperative radiotherapy was planed. The patient deteriorated rapidly and died, about 6 months after the disease had been diagnosed. Conclusion. Extrahepatic metastasis of HCC represents a progressive phase of the disease with poor prognosis, so the main aim of the treatment should be palliation and care of symptoms.

scholarly journals Overexpression of SKA3 correlates with poor prognosis in female early breast cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12506
Author(s):  
Yue Zhong ◽  
Zhenjie Zhuang ◽  
Peiju Mo ◽  
Mandi Lin ◽  
Jiaqian Gong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Molecular Subtype ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Chi Square ◽  
Exact Test ◽  
Chi Square Test

Background Spindle and kinetochore associated complex subunit 3 (SKA3) plays an important role in tumorigenesis and the progression of various tumors. But the relationship between SKA3 and early breast cancer remains unclear. The study aimed to explore the prognostic significance of SKA3 in breast cancer. Methods In the study, SKA3 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas database (TCGA). Then, we presented validation results for RT-qPCR (quantitative reverse transcription PCR) and ELISA (enzyme-linked immunosorbent assay). The relationship between clinical characteristics and SKA3 expression was assessed by Chi-square test and Fisher’s exact test. Kaplan–Meier method and Cox regression analysis were conducted to evaluate the prognostic value of SKA3. Gene set enrichment analysis (GSEA) was performed to screen biological pathways using the TCGA dataset. Besides, single sample gene set enrichment analysis (ssGSEA) was utilized to identify immune infiltration cells about SKA3. Results SKA3 mRNA was expressed at high levels in breast cancer tissues compared with normal tissues. Chi-square test and Fisher’s exact test showed SKA3 expression was related to age, tumor (T) classification, node (N) classification, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PR), molecular subtype, and race. RT-qPCR results showed that SKA3 expression was overexpressed in ER, PR status, and molecular subtype in Chinese people. Kaplan–Meier curves implicated that high SKA3 expression was related to a poor prognosis in female early breast cancer patients. Cox regression models showed that high SKA3 expression could be used as an independent risk factor for female early breast cancer. Four signaling pathways were enriched in the high SKA3 expression group, including mTORC1 signaling pathway, MYC targets v1, mitotic spindle, estrogen response early. Besides, the SKA3 expression level was associate with infiltrating levels of activated CD4 T cells and eosinophils in breast cancer. Conclusion High SKA3 expression correlates with poor prognosis and immune infiltrates in breast cancer. SKA3 may become a biomarker for the prognosis of breast cancer.

scholarly journals Prognostic implications of cell division cycle protein 45 expression in hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10824
Author(s):  
Chen Yang ◽  
shufang Xie ◽  
Yi Wu ◽  
Guoqing Ru ◽  
Xianglei He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Division ◽  
Dna Replication ◽  
Chemical Carcinogenesis ◽  
Cell Division Cycle ◽  
Functional Enrichment ◽  
Functional Annotations ◽  
Normal Tissues ◽  
Prognostic Implications ◽  
Tissue Specimens

Background The overall prognosis of hepatocellular carcinoma (HCC) is poor and novel prognostic biomarkers might better monitor the progression of HCC. Cell division cycle protein 45 (CDC45) plays a key role in DNA replication and considered to be involved in tumorigenesis. This study investigated CDC45 expression in tumour tissues and defined its prognostic value in HCC patients. Methods We used immunohistochemistry (IHC) staining to examine the expression of CDC45 in tumour tissue specimens and compare them with adjacent normal tissue specimens using a constructed tissue microarray (TMA) and analyzed how clinical features are related to HCC prognosis. Functional enrichment analyses were used to describe significantly involved hallmark pathways of differentially expressed genes (DEGs, which were screened out according to the high or low expression of CDC45 in tumour tissues). Results Our findings showed that the proteome expression of CDC45 was evidently downregulated in HCC tissues compared with matched normal tissues (P < 0.0001). Although we did not find any differences in terms of vascular invasion, metastasis, lymphatic infiltration, or Edmondson grade between patients with high and low CDC45 expression, low CDC45 expression was significantly correlated with microvascular invasion (P = 0.046). Multivariate analysis indicated that CDC45 expression (P = 0.035) was an independent prognostic factor for the overall survival (OS) rate of HCC patients. Patients with CDC45 expression was positively correlated with OS rates among HCC patients (P < 0.05). Functional annotations indicated that CDC45 is involved in the most significant pathways, including the cell cycle, DNA replication, chemical carcinogenesis and drug metabolism–cytochrome P450 pathways. Discussion Our findings showed that low proteomic level of CDC45 was associated with a poor prognosis in HCC patients, indicating that CDC45 might be a novel prognostic marker.

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