scholarly journals High Expression Levels of SLC38A1 Are Correlated with Poor Prognosis and Defective Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yun Liu ◽  
Yong Yang ◽  
Linna Jiang ◽  
Hongrui Xu ◽  
Junwei Wei
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Protein Expression ◽  
Prognostic Significance ◽  
Functional Enrichment ◽  
High Expression ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Mrna And Protein Expression

Solute Carrier Family 38 Member 1 (SLC38A1) is a principal transporter of glutamine and plays a crucial role in the transformation of neoplastic cells. However, the correlation between SLC38A1 expression, prognosis, and immune infiltration in hepatocellular carcinoma (HCC) has yet to be elucidated. We used two independent patient cohorts, namely, a Cancer Genome Atlas (TCGA) cohort and a Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort, to analyze the role of SLC38A1 in HCC at the mRNA and protein levels, respectively. In these two cohorts, SLC38A1 mRNA and protein expression levels were higher in HCC tissues than in adjacent nontumor tissues. Both SLC38A1 mRNA and protein expression were positively associated with clinicopathological characteristics (clinical stage, T stage, pathological grade, tumor size, and tumor thrombus), were negatively associated with survival, and were independent prognostic factors in HCC patients. Functional enrichment analyses further indicated that SLC38A1 was involved in multiple pathways related to amino acid metabolism, tumors, and immunity. High expression levels of SLC38A1 were inversely proportional to CD8+ T cells and directly proportional to macrophages M0, neutrophils, programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Moreover, we used immunohistochemical analysis of tissue samples and other online databases to further validate the expression levels and prognostic significance of SLC38A1 in HCC. Collectively, our study demonstrated that the upregulated expression of SLC38A1 was related to an unfavorable prognosis and defective immune infiltration in HCC.

scholarly journals High Expression of LTBP2 Contributes to Poor Prognosis in Colorectal Cancer Patients and Correlates with the Mesenchymal Colorectal Cancer Subtype

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Huang ◽  
Guihua Wang ◽  
Chunmei Zhao ◽  
Rong Geng ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Protein Expression ◽  
Mrna Expression ◽  
Cell Lines ◽  
Critical Role ◽  
Prognostic Significance ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
Mrna And Protein Expression

Colorectal cancer (CRC) is a complex and heterogeneous disease with four consensus molecular subtypes (CMS1-4). LTBP2 is a member of the fibrillin/LTBP super family and plays a critical role in tumorigenesis by activating TGF-β in the CMS4 CRC subtype. So far, the expression and prognostic significance of LTBP2 in CRC remains obscure. In this study, we aimed to analyze the mRNA and protein expression levels of LTBP2 in CRC tissues and then estimate their values as a potential prognostic biomarker. We detected the mRNA expression of LTBP2 in 28 cases of fresh CRC tissues and 4 CRC cell lines and the protein expression of LTBP2 in 483 samples of CRC tissues, matched tumor-adjacent tissues, and benign colorectal diseases. LTBP2 protein expression was then correlated to patients’ clinical features and overall survival. Both LTBP2 mRNA and protein expression levels in CRC tissues were remarkably superior to those in adjacent normal colorectal tissues (P=0.0071 and P<0.001, respectively), according to TCGA dataset of CRC. High LTBP2 protein expression was correlated with TNM stage (P<0.001), T stage (P<0.001), N stage (P<0.001), and M stage (P<0.001). High LTBP2 protein expression was related to poor overall survival in CRC patients and was an independent prognostic factor for CRC. LTBP2 mRNA expression was especially higher in the CMS4 subtype (P<0.001), which was confirmed in CRC cell lines. Our data suggested that LTBP2 may act as an oncogene in the development of colorectal cancer and have important significance in predicting CRC prognosis. LTBP2 could be a novel biomarker and potential therapeutic target for mesenchymal colorectal cancer and can improve the outcome of high-risk CRC.

scholarly journals Clinical significance of high expression of stanniocalcin-2 in hepatocellular carcinoma

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Yuan Wang ◽  
Jian Wu ◽  
Jiangyan Xu ◽  
Shengyou Lin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Portal Vein ◽  
Protein Expression ◽  
High Expression ◽  
Tumor Diameter ◽  
Tumor Differentiation ◽  
Rt Pcr ◽  
Mrna And Protein Expression ◽  
Stanniocalcin 2

Abstract To investigate the significance of stanniocalcin-2 (STC2) expression in hepatocellular carcinoma (HCC) tissues and adjacent tissues. Levels of STC2 in HCC tissue were detected in 200 HCC patients tissues and adjacent tissues as controls by immunohistochemistry technique (IHC) and reverse transcriptase-PCR (RT-PCR). Single factor analysis was used to study the relationship between expression of STC2 mRNA and protein and clinicopathological features of HCC. Multifactor Cox survival analysis was used to relationship between the expression of STC2 and overall survival of postoperative patients with HCC. IHC staining showed that the expression of STC2 protein rate was 81.00% (163/200). And the positive rate of adjacent tissues was 29.00% (58/200). Western blot showed that the expression of STC2 protein in HCC was significantly higher than that in the adjacent tissues (P<0.05). RT-PCR showed that the positive rates of STC2 mRNA expression in HCC were 75.50% (151/200), which was significantly higher than that in adjacent tissues 14.50% (29/200) (P<0.05). Both STC2 mRNA and protein expression are related to tumor diameter, stage, tumor metastasis, carcinoma emboli in the portal vein and the degree of tumor differentiation in HCC. The HCC patients with higher expression of STC2 had shorter median survival time. STC2 expression, tumor diameter, carcinoma emboli in the portal vein, tumor differentiation degree, and tumor stage were independent factors affecting the overall survival of postoperative patients. The high expression of STC2 mRNA and protein expression in HCC may be associated with the occurrence, development, and prognosis of HCC. STC2 may also be possible to help developing new therapeutic strategies for HCC.

scholarly journals Identification of Therapeutic Targets and Prognostic Biomarkers among Genes from the Mediator Complex Family in the Hepatocellular Carcinoma Tumour-Immune Microenvironment

2022 ◽  
Vol 2022 ◽  
pp. 1-22
Author(s):  
Wei Tan ◽  
Shuai Peng ◽  
Zhuokai Li ◽  
Ruiqian Zhang ◽  
Yangrui Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Functional Enrichment ◽  
High Expression ◽  
Mediator Complex ◽  
Immune Microenvironment ◽  
Expression Levels ◽  
Study Results ◽  
Liver Cancers

Background. Hepatocellular carcinoma (HCC) is predominant among all types of primary liver cancers characterised by high morbidity and mortality. Genes in the mediator complex (MED) family are engaged in the tumour-immune microenvironment and function as regulatory hubs mediating carcinogenesis and progression across diverse cancer types. Whereas research studies have been conducted to examine the mechanisms in several cancers, studies that systematically focused on the therapeutic and prognostic values of MED in patients with HCC are limited. Methods. The online databases ONCOMINE, GEPIA, UALCAN, GeneMANIA, cBioPortal, OmicStudio, STING, Metascape, and TIMER were used in this study. Results. The transcriptional levels of all members of the MED family in HCC presented an aberrant high expression pattern. Significant correlations were found between the MED1, MED6, MED8, MED10, MED12, MED15, MED17, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, and MED27 expression levels and the pathological stage in the patients with HCC. The patients with high expression levels of MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 were significantly associated with poor prognosis. Functional enrichment analysis revealed that the members of the MED family were mainly enriched in the nucleobase-containing compound catabolic process, regulation of chromosome organisation, and transcriptional regulation by TP53. Significant correlations were found between the MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 expression levels and all types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). B cells and MED8 were independent predictors of overall survival. We found significant correlations between the somatic copy number alterations of the MED6, MED8, MED10, MED20, MED21, MED22, MED24, and MED25 molecules and the abundance of immune infiltrates. Conclusions. Our study delineated a thorough landscape to investigate the therapeutic and prognostic potentials of the MED family for HCC cases, which yielded promising results for the development of immunotherapeutic drugs and construction of a prognostic stratification model.

scholarly journals Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Complex ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Prognostic Biomarkers ◽  
High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

scholarly journals Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nghiem Xuan Hoan ◽  
Pham Thi Minh Huyen ◽  
Mai Thanh Binh ◽  
Ngo Tat Trung ◽  
Dao Phuong Giang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Disease Progression ◽  
Infection Risk ◽  
Hbv Infection ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Programmed Cell Death 1

AbstractThe inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.

scholarly journals Study of Gene Expression of Programmed Cell Death Ligand 1 (PD-L1) in Breast Cancer Patients

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 2-2
Author(s):  
H Gadelrab ◽  
M Mokhtar ◽  
H Morsy ◽  
M Elnaggar
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Patients ◽  
Therapeutic Response ◽  
Female Breast Cancer ◽  
Clinicopathological Parameters ◽  
Breast Cancer Patients ◽  
Expression Levels ◽  
Female Breast

Introduction: Breast cancer is the most frequently occurring cancer among females and the second most common cancer overall. Programmed Cell Death Ligand 1 (PD-L1) plays an important role in blocking ‘cancer-immunity cycle’ and is considered as a major inhibitory pathway. The aim of the present study was to clarify the alterations of expression of PD-L1 in peripheral blood mononuclear cytes (PBMCs) of female breast cancer patients and analyze its association with clinico-pathological criteria as well as therapeutic response. Materials and Methods: The study was conducted on 45 female breast cancer patients and 45 female controls. Blood samples were collected followed by PBMCs isolation, total RNA extraction, reverse transcription and finally, quantitative polymerase chain reaction (qPCR) using SYBR Green DNA binding dye. Expression levels of PD-L1 were calculated and then compared with clinicopathological parameters of the patients in addition to initial therapeutic response. Results: A significant difference was detected for PD-L1 expression levels in breast cancer patients compared to controls. A significant association with age, metastatic breast cancer, estrogen receptor (ER) negative status as well as high concentrations of cancer antigen 15-3 (CA15-3) was detected. On the other hand, no significant association was recognized with tumor size, lymph nodal status, histopathological type, grade, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER-2) status, triple negative, among de novo and recurrent metastatic patients and for the number of metastatic sites as well as the therapeutic response. Conclusions: This study paves the way of the use of PD-L1 as a noninvasive prognostic and diagnostic biomarker for poor prognosis of breast cancer.

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