The diagnostic and prognostic significance of small nuclear ribonucleoprotein Sm D1 aberrantly high expression in hepatocellular carcinoma

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.

Download Full-text

Expression of CD24 as a predictor of prognosis of hepatocellular carcinoma after operation

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22043 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22043-e22043 ◽

Cited By ~ 1

Author(s):

J. Fan ◽

X. Yang ◽

Y. Xu ◽

Y. Shi ◽

J. Zhou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Significance ◽

Metastatic Potential ◽

Early Recurrence ◽

High Expression ◽

Nuclear Accumulation ◽

Recurrence Time ◽

Prognostic Information ◽

Tumor Tissues

e22043 Background: CD24 expression has previously been reported in hepatocellular carcinoma (HCC), although little is known about its prognostic significance. The aim of this study is to evaluate the relation of CD24 expression and its prognostic significance in HCC. Methods: CD24 expression in stepwise metastatic HCC cell lines and tumor tissues from 50 HCC patients was investigated by quantitative real-time reverse transcription-PCR and Western blot analyses. The role of CD24 was investigated by depletion CD24 expression in HCC cells through small-interfering RNA. Tumor tissue microarrays of 314 HCC patients who underwent resection between 1997 and 2000 were used to detect the expressions of CD24, β-catenin and PCNA expression. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Results: CD24 was overexpressed in the high metastatic HCC cell line and in tumor tissues of recurrent patients. Depletion of CD24 caused a notable decrease in cell proliferation, migration and invasiveness in vitro. CD24 was confirmed as an independent predictor for overall survival (p<0.001) and relapse-free survival (p<0.001), regardless of recurrence time, AFP level, TNM stage and Edmondson stage. High expression of CD24 in HCC tissues was significantly associated cytoplasmic/nuclear accumulation of β-catenin (p=0.023), high tumor proliferate status (p=0.018) and diffused intrahepatic recurrence and distance metastasis (p=0.026). Adjuvant TACE after operation reduced the early recurrence (≤1 year) in CD24+ HCC patients (p=0.024), while there had no significant changes in CD24- patients (p=0.284). Conclusions: High expression levels of CD24 were related with high invasive and metastatic potential, high tumor proliferation status and activation of Wnt/β-catenin pathway. The expression of CD24 provides new prognostic information about HCC prognosis and targeted therapy to CD24+fraction in HCC may comprise a promising anti-recurrence strategy for HCC patients after surgery. No significant financial relationships to disclose.

Download Full-text

FAM83D is associated with gender, AJCC stage, overall survival and disease-free survival in hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20181640 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 2

Author(s):

Xuling Liu ◽

Hong Gao ◽

Jie Zhang ◽

Dongying Xue

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Sequence Similarity ◽

Prognostic Significance ◽

Disease Free Survival ◽

High Expression ◽

Mrna Levels ◽

Free Survival ◽

Ajcc Stage ◽

Disease Free

AbstractPrognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.

Download Full-text

Enhanced expression of miR-889 forecasts an unfavorable prognosis and facilitates cell progression in hepatocellular carcinoma

Diagnostic Pathology ◽

10.1186/s13000-021-01111-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

He Wang ◽

Huiwen Wang ◽

Wenyu Cui ◽

Qiao Zhang ◽

Jing Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Cell Lines ◽

Cox Regression ◽

Malignant Tumors ◽

Prognostic Significance ◽

High Expression ◽

Migration And Invasion ◽

Pcr Analysis ◽

Cox Regression Analysis

Abstract Background As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma. Methods Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability. Results The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro. Conclusions Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.

Download Full-text

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

Journal of Oncology ◽

10.1155/2021/5680968 ◽

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.

Download Full-text

N6-methyladenosine (m6A) RNA methylation regulator SNRPC is a prognostic biomarker and is correlated with immunotherapy in hepatocellular carcinoma

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02354-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jihao Cai ◽

Minglei Zhou ◽

Jianxin Xu

Keyword(s):

Hepatocellular Carcinoma ◽

Specific Protein ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Rna Methylation ◽

Gene Set ◽

Normal Tissues ◽

Small Nuclear Ribonucleoprotein ◽

Protein Components ◽

Nuclear Ribonucleoprotein

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and due to its complex pathogenic factors, its prognosis is poor. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression, and prognosis of many tumors. The m6A RNA methylation regulator small nuclear ribonucleoprotein polypeptide C (SNRPC), which encodes one of the specific protein components of the U1 small nuclear ribonucleoprotein (snRNP) particle, has been proven to be related to the prognosis of patients with HCC. However, the effect of SNRPC on the tumor microenvironment and immunotherapy in HCC remains unclear. Case presentation The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI-JP samples, respectively, were used in this study. Both the expression of SNRPC in HCC was upregulated in the TCGA and ICGC databases compared to normal tissues. Next, the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By gene set variation (GSVA) analysis and gene set enrichment (GSEA) analysis, we found that SNRPC was mainly related to protein metabolism and the immune process. Furthermore, the estimation of stromal and immune cells in malignant tumor tissues using expression (ESTIMATE), microenvironment cell population counter (MCP-counter), and single sample GSEA (ssGSEA) algorithms revealed that the high-SNRPC group had a lower stromal score, lower abundance of endothelial cells and fibroblasts, and lower immune infiltration. Ultimately, a tumor immune dysfunction and exclusion (TIDE) analysis revealed that patients in the low-SNRPC group may be more sensitive to immune checkpoint inhibitor therapy. Conclusion SNRPC could serve as a promising prognostic and immunotherapeutic marker in HCC and might contribute to new directions and strategies for HCC treatment.

Download Full-text