Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

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NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20180907 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 1

Author(s):

Ji-sheng Jing ◽

Hongbo Li ◽

Shun-cai Wang ◽

Jiu-ming Ma ◽

La-qing Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Survival Curve ◽

Disease Free Survival ◽

Prognostic Indicator ◽

Clinicopathological Characteristics ◽

Pcr Analysis ◽

Kaplan Meier ◽

Tumor Tissues ◽

The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

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Impact of CKLF-like MARVEL Transmembrane Domain Containing 6 (CMTM6) Expression in Gastric Cancer

10.21203/rs.3.rs-48504/v1 ◽

2020 ◽

Author(s):

M Nishi ◽

Mitsuo Shimada ◽

Kozo Yoshikawa ◽

Jun Higashijima ◽

Takuya Tokunaga ◽

...

Keyword(s):

Gastric Cancer ◽

Transmembrane Domain ◽

Disease Free Survival ◽

University Hospital ◽

High Expression ◽

High Expression Group ◽

Group 5 ◽

Relationship Of ◽

The Relationship ◽

Low Expression

Abstract Background: CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1(PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods: A total of 105 patients who had undergone curative surgical resection for stage II/III GC at Tokushima University Hospital were included in this study. The expression of CMTM and PD-L1 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results: CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS: 57.2% vs. 79.2%, respectively; p<0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS: 52.8% vs. 72.4%, respectively; p=0.20). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p<0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p=0.07), and PD-L1 expression was positively correlated with PD-1 expression (p<0.05).Conclusions: CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC.

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High Expression of ANXA2 Pseudogene ANXA2P2 Promotes an Aggressive Phenotype in Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2019/9267046 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Qiu-shuang Wang ◽

Liang-Liang Shi ◽

Fei Sun ◽

Yi-fan Zhang ◽

Ren-Wang Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Disease Free Survival ◽

Annexin A2 ◽

The Cancer Genome Atlas ◽

High Expression ◽

Migration And Invasion ◽

Targeted Drugs ◽

Noncancerous Tissue ◽

Expression Levels ◽

Hcc Cells

Objective. Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2 (annexin A2 pseudogene 2) is one of three pseudogenes of annexin A2 that have recently been shown to be aberrantly transcribed in hepatocellular carcinoma (HCC) cells. However, its clinical meaning and biological function in HCC have remained unclear. Therefore, the present study was aimed at exploring the prognostic value of a high expression of ANXA2P2 in HCC tissue and at identifying whether it can affect the efficacy of targeted drugs (sorafenib, regorafenib, and lenvatinib). Methods. We obtained ANXA2P2 mRNA expression levels from The Cancer Genome Atlas (TCGA) RNA sequence database. The expression levels of ANXA2P2 in 49 pairs of intratumoral and peritumoral liver tissues were examined by RT-PCR. Wound healing and transwell assays were performed to confirm the tumor-promoting properties of ANXA2P2 in HCC cells. CCK8 assay was conducted to identify whether ANXA2P2 can affect the growth of HCC cells when administered with targeted drugs (sorafenib, regorafenib, and lenvatinib). Results. The expression of ANXA2P2 in HCC tissues was significantly higher than that in adjacent cancerous tissues from TCGA database and validation group. Additionally, patients with high ANXA2P2 expression in HCC tissue had a shorter overall survival, whereas no statistically significant correlation was found between ANXA2P2 expression and disease-free survival (p=0.08) as well as other clinical parameters, such as age, gender, histological grade, T classification, stage, albumin level, alpha-fetoprotein, and vascular invasion (p=0.7323, 0.8807, 0.5762, 0.8515, 0.7113, 0.242, 1.0000, and 0.7685, respectively). Furthermore, in vitro experiments showed that knockdown of ANXA2P2 inhibited migration and invasion of HCC cells but did not have an influence on the HCC cell proliferation when treated with targeted drugs (sorafenib, regorafenib, and lenvatinib). Conclusion. Our study confirmed elevated ANXA2P2 expression levels in HCC tissue compared with adjacent noncancerous tissue and a worse prognosis of patients with high ANXA2P2 levels in the HCC tissue. The newly found properties of promoting migration and invasion of ANXA2P2 in HCC help to explain this phenomenon. ANXA2P2 could be a novel and suitable predicative biomarker for the risk assessment of recurrence or metastasis of HCC patients but may not be effective to predict the efficacy of targeted drugs.

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Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

10.21203/rs.3.rs-471663/v1 ◽

2021 ◽

Author(s):

Yanghui Wen ◽

Hui Su ◽

Wuke Wang ◽

Feng Ren ◽

Haitao Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Expression Profiles ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Chi Square ◽

Kaplan Meier ◽

Chi Square Test ◽

Liver Hepatocellular Carcinoma ◽

The Relationship

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.

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Co-expression of CMTM6 and PD-L1: a novel prognostic indicator of gastric cancer

10.21203/rs.2.24485/v1 ◽

2020 ◽

Author(s):

Chao Zhang ◽

Wen An ◽

Yuen Tan ◽

Huimian Xu

Keyword(s):

Gastric Cancer ◽

Survival Data ◽

Transmembrane Domain ◽

Prognostic Indicator ◽

Clinicopathological Characteristics ◽

High Expression ◽

Rank Test ◽

Chi Square ◽

Borrmann Type ◽

Chi Square Test

Abstract Background CKLF Like MARVEL Transmembrane Domain Containing 6 (CMTM6) is involved in the epigenetic regulation of genes and tumorigenesis. Programmed cell death ligand 1 (PD-L1) is closely related to the prognosis of some human cancers. CMTM6 is a key regulator of PD-L1 in many cancers. The purpose of this study was to investigate the expressions of these proteins in gastric cancer and the correlations with clinicopathological features and survival. Methods The expression levels of CMTM6 and PD-L1 were examined in 185 gastric cancer specimens by immunohistochemistry. Chi-square test was used to analyze the relationship between CMTM6 and PD-L1 expressions and clinicopathological characteristics. Kaplan-Meier method and log-rank test were used to analyze the survival data of patients.Results The positive expression rates of CMTM6 and PD-L1 were 78.38% (145/185) and 75.68% (140/185), respectively. High expression of CMTM6 and PD-L1 was correlated with Borrmann type ( P < 0.001), N stage ( P = 0.002), peritoneal metastasis ( P = 0.007) and TNM stage ( P = 0.038). The expression of CMTM6 and PD-L1 in gastric cancer tissues was positively correlated (Pearson's coefficient test, r = 0.260; P < 0.001). High expression of CMTM6 was correlated with poor prognosis (HR = 1.668; 95% CI = 1.032–2.695; P = 0.037). High expression of both CMTM6 and PD-L1 could be used as an independent factor for overall survival (HR = 1.554; 95% CI = 1.011–2.389; P = 0.044). Conclusions The combined detection of CMTM6 and PD-L1 may be used as an indicator for judging the prognosis of gastric cancer.

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Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.637971 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yu Pan ◽

Geng-yuan Hu ◽

Shi Jiang ◽

Shun-jie Xia ◽

Hendi Maher ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Aerobic Glycolysis ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Free Survival ◽

Sorafenib Therapy ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Advanced Stages ◽

Disease Free

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

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Expression and Significance of LncRNA-MINCR and CDK2 mRNA in Primary Hepatocellular Carcinoma

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190404151020 ◽

2019 ◽

Vol 22 (3) ◽

pp. 201-206

Author(s):

Jiangshan Lian ◽

Xiaolin Zhang ◽

Yingfeng Lu ◽

Shaorui Hao ◽

Zhe Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Lymph Node ◽

Survival Rate ◽

Lymph Node Metastasis ◽

Mrna Expression ◽

Primary Hepatocellular Carcinoma ◽

High Expression ◽

Node Metastasis ◽

The Relationship ◽

Low Expression

Objective: To investigate the expression of long-chain non-coding RNA MINCR (LncRNAMINCR) and Cyclin-Dependent Kinase 2 (CDK2) mRNA in primary hepatocellular carcinoma, and to analyze the relationship between its expression and clinical pathological parameters and prognosis of hepatocellular carcinoma. Methods: Seventy-five surgically resected primary hepatocellular carcinoma tissues and paracancerous tissues were selected. Real-time PCR was used to detect the expression of LncRNA-MINCR and CDK2 mRNA in hepatocellular carcinoma tissues and adjacent tissues. The relationship of clinicopathological parameters and prognosis between hepatocellular carcinoma and LncRNA-MINCR and CDK2 mRNA were analyzed. Pearson correlation coefficient describes the correlation between LncRNA-MINCR and CDK2 mRNA. Results: The expression of LncRNA-MINCR and CDK2 mRNA in primary hepatocellular carcinoma tissues was higher than that in the adjacent tissues [(5.51±0.62) vs (1.62±0.51), (4.52±0.73) vs (1.85±0.95), P<0.05]. The expression of LncRNA-MINCR in the primary hepatocellular carcinoma group was positively correlated with CDK2 mRNA (r=0.352, P<0.05), and the expression of LncRNA-MINCR in the paracancerous tissue group was not correlated with CDK2 mRNA (r=0.024, P>0.05). LncRNA-MINCR expression was associated with TNM staging, lymph node metastasis, and cirrhosis (P<0.05). CDK2 mRNA expression was associated with tumor diameter, TNM stage, lymph node metastasis, and serum alpha-fetoprotein levels (P<0.05). The 3-year survival rate of patients with high expression of LncRNAMINCR was lower than that of LncRNA-MINCR low expression group [53.49% vs 77.38%, 2=13.024, P<0.05). The 3-year survival rate of patients with high CDK2 mRNA expression was lower than that of CDK2 mRNA low expression group [51.29] % vs 80.38%, 2 = 10.15, P < 0.05]. Conclusion: The expression of LncRNA-MINCR and CDK2 mRNA in primary hepatocellular carcinoma tissues increased significantly. The two play a synergistic role in the invasion, invasion and metastasis of hepatocarcinoma cells. High expression of LncRNA-MINCR and CDK2 mRNA indicates poor prognosis in patients with hepatocellular carcinoma.

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CDKN3 expression predicates poor prognosis and regulates adriamycin sensitivity in hepatocellular carcinoma in vitro

Journal of International Medical Research ◽

10.1177/0300060520936879 ◽

2020 ◽

Vol 48 (7) ◽

pp. 030006052093687

Author(s):

Wei Dai ◽

Shuo Fang ◽

Guanhe Cai ◽

Jialiang Dai ◽

Guotai Lin ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Prognostic Factor ◽

Therapeutic Target ◽

Bioinformatics Analysis ◽

Kinase Inhibitor ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

The Relationship

Objective Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. This study investigated the relationship between cyclin-dependent kinase inhibitor (CDKN)3 and prognosis and pathological characteristics in HCC patients to determine whether it could be used as a prognostic factor and/or therapeutic target for HCC drug development. Methods We previously showed that CDKN3 is deregulated in HCC tumor samples. Here, bioinformatics analysis was used to assess the relationship between CDKN3 gene expression and the characteristics of HCC patients from Gene Expression Omnibus and The Cancer Genome Atlas databases. Additionally, CDKN3 expression was silenced by small interfering RNA to determine its effect on HCC cell proliferation and on HCC cell sensitivity to adriamycin chemotherapy. Results Bioinformatics analysis showed a negative correlation between CDKN3 expression and both disease-free survival and overall survival. CDKN3 silencing did not significantly suppress the proliferation of HCC cells, but did decrease their sensitivity to adriamycin. Conclusions CDKN3 may have a dual role during the development of HCC, and could be used as an independent prognostic factor and therapeutic target for HCC treatment.

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Prognostic roles of the transcriptional expression of exportins in hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20190827 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 2

Author(s):

Lubiao Chen ◽

Yanlin Huang ◽

Liang Zhou ◽

Yifan Lian ◽

Jialiang Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Survival Data ◽

Disease Free Survival ◽

Dna Amplification ◽

Genetic Alterations ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

High Expression ◽

Poor Overall Survival ◽

Cancer Tissues

Abstract Aims: A large number of studies have suggested that exportins (XPOs) play a pivotal role in human cancers. In the present study, we analyzed XPO mRNA expression in cancer tissues and explored their prognostic value in hepatocellular carcinoma (HCC). Methods: Transcriptional and survival data related to XPO expression in HCC patients were obtained through the ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Gene Expression Profiling Interactive Analysis (GEPIA). Sequence alteration data for XPOs were obtained from The Cancer Genome Atlas (TCGA) database and c-BioPortal. Gene functional enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: Compared with normal liver tissues, significant XPO mRNA overexpression was observed in HCC cancer tissues. There was a trend of higher XPO expression in more advanced clinical stages and lower differentiated pathological grades of HCC. In HCC patients, high expression of XPO1, CSE1L, XPOT, XPO4/5/6 was related to poor overall survival (OS), and XPO1, CSE1L and XPO5/6 were correlated with poor disease-free survival (DFS). The main genetic alterations in XPOs involved mRNA up-regulation, DNA amplification and deletion. General XPO mutations were remarkably associated with worse OS and mostly affected the pathways of RNA transport and oocyte meiosis. Conclusion: High expression of XPOs was associated with a poor prognosis in HCC patients. XPOs may be exploited as good prognostic biomarkers for survival in HCC patients.

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Evaluation of the Therapeutic Effect of Adjuvant Transcatheter Arterial Chemoembolization Based on Ki67 After Hepatocellular Carcinoma Surgery

Frontiers in Oncology ◽

10.3389/fonc.2021.605234 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yu-Fei Zhao ◽

Xiu Xiong ◽

Kai Chen ◽

Wei Tang ◽

Xu Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcatheter Arterial Chemoembolization ◽

Tumor Resection ◽

High Expression ◽

Ki67 Expression ◽

High Expression Group ◽

Significant Difference ◽

The Relationship ◽

Low Expression ◽

Arterial Chemoembolization

Background and aimsThis study aimed to determine the relationship between Ki67 expression and the efficacy of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in patients with hepatocellular carcinoma.MethodsThe Kaplan-Meier method was used to analyze the recurrence-free survival (RFS) and overall survival (OS) rates between the sub-groups in the ki67 low expression group and the ki67 high expression group and analyze the relationship between the expression of Ki67 and the efficacy of TACE.ResultsAfter PSM, there was no significant difference in the RFS and OS between the surgery + TACE and surgery subgroups after 1, 2, or 3 years (RFS: 63.9%, 55.6%, and 42.9% vs. 83.3%, 63.9%, and 55.6%, respectively, P = 0.279; OS: 91.7%, 83.3%, and 74.3% vs. 91.7%, 88.9%, and 71.4%, respectively, P = 0.890) in the Ki67 low-expression group. The RFS and OS were higher in the surgery + TACE subgroup than the surgery subgroup after 1, 2, and 3 years (RFS: 80.0%, 77.5%, and 69.2% vs. 53.5%, 39.5%, and 32.6%, respectively, P<0.001; OS: 97.5%, 85.0%, and 79.5% vs. 79.1%, 48.8%, and 42.9%, respectively, P = 0.001) in the Ki67 high expression group. The RFS was higher in the Ki67 high-expression subgroup than the low-expression subgroup after 1, 2, and 3 years, and OS had no significant difference (RFS: 80.0%, 79.5%, and 69.2% vs. 67.4%, 56.5%, and 46.7%, respectively, P = 0.035; OS: 97.5%, 85.0%, and 79.5% vs. 93.5%, 82.6%, and 75.6%, respectively, P = 0.665) in the surgery + TACE group.ConclusionsFor patients with hepatocellular carcinoma and high expression of Ki67 (Ki67≥20%), adjuvant hepatic artery chemoembolization after radical liver tumor resection effectively reduced the probability of tumor recurrence after surgery and prolonged the OS of patients. High Ki67 expression during the post-operative follow-up evaluation of hepatocellular carcinoma patients is an indicator for adjuvant TACE therapy.

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