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

2019 ◽  
Vol 39 (5) ◽  
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.

scholarly journals Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transmembrane Domain ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Chi Square ◽  
Tumor Tissues ◽  
The Relationship ◽  
Low Expression

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.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
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.

scholarly journals CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Gene Markers ◽  
Free Survival ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

scholarly journals Incidence and Prognostic Significance of PD-L1 Expression in High-Grade Salivary Gland Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Qigen Fang ◽  
Yao Wu ◽  
Wei Du ◽  
Xu Zhang ◽  
Defeng Chen
Keyword(s):  
Salivary Gland ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
High Grade ◽  
Salivary Gland Carcinoma ◽  
Gland Carcinoma ◽  
The Difference

ObjectivePD-L1 is one of the predictors of immunotherapy efficacy. Our goal was to analyze its expression and prognostic significance in high-grade salivary gland carcinoma (SGC).MethodsPD-L1 expression was evaluated using paraffin-embedded specimens from patients with surgically treated high-grade SGC, and it was scored by the tumor proportion score (TPS), combined positive score (CPS), and immune cell (IC) score. Associations between clinicopathological variables, disease-free survival (DFS), overall survival (OS) and PD-L1 expression were assessed.ResultsTPS≥1% occurred in 47 patients with an incidence of 43.1%, and it was significantly related to an advanced tumor stage. In patients with TPS&lt;1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year DFS rates were 36%, 26%, and 13%, respectively, and the difference was significant. In patients with TPS&lt;1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year OS rates were 49%, 24%, and 13%, respectively, and the difference was significant. CPS≥1 occurred in 87 patients with an incidence of 79.8%. IC scores of 0, 1, 2, and 3 were noted in 24 (22.0%), 37 (33.9%), 31 (28.4%), and 17 (15.6%) patients, respectively. Both CPS and IC scores had no impact on DFS or OS.ConclusionsThe expression of PD-L1 in tumor cells of high-grade SGCs was not uncommon, and it was significantly associated with tumor stage. PD-L1 expression in tumor cells rather than in immune cells indicated a poor prognosis.

scholarly journals Novel Value of Preoperative Gamma-Glutamyltransferase Levels in the Prognosis of AFP-Negative Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Liang-He Lu ◽  
Wei-Wei ◽  
Anna Kan ◽  
Jie-Mei ◽  
Yi-Hong Ling ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariable Analysis ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Burden ◽  
Optimal Cutoff ◽  
Gamma Glutamyltransferase ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background. Gamma-glutamyltransferase (GGT) is involved in tumor development and progression, but its prognostic value in α-fetoprotein- (AFP-) negative (AFP<25 ng/mL) hepatocellular carcinoma (HCC) patients remains unknown. Methods. A large cohort of 678 patients with AFP-negative HCC following curative resection who had complete data were enrolled in this study. The optimal cutoff value for the preoperative level of GGT was determined by the X-tile program. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were also identified. Results. The optimal cutoff values for the preoperative levels of GGT were 37.2 U/L and 102.8 U/L, which were used to divide all patients into three subgroups (group 1, GGT<37.2 U/L (n=211, 31.1%); group 2, GGT≥37.2 and <102.8 U/L (n=320, 47.2%); group 3, GGT≥102.8 U/L (n=147, 21.7%)), with distinct OS times (58.5 vs. 53.5 vs. 44.4 months, P<0.001) and DFS times (47.9 vs. 40.3 vs. 30.1 months, P<0.001). Elevated preoperative GGT levels were associated with an unfavorable tumor burden (larger tumor size, multiple tumors, and microvascular invasion) and were selected as independent predictors of a worse OS (group 2 vs. group 1, HR: 1.73 (1.13-2.65), P=0.011; group 3 vs. group 1, HR: 3.28 (2.10-5.13), P<0.001) and DFS (group 2 vs. group 1, HR: 1.52 (1.13-2.05), P=0.006; group 3 vs. group 1, HR: 2.11 (1.49-2.98), P<0.001) in multivariable analysis. Conclusions. Elevated preoperative GGT levels are associated with an unfavorable tumor burden and serve as an independent prognostic marker for worse outcomes in AFP-negative HCC patients following resection.

scholarly journals Elevated Preoperative Serum CA19-9 Levels in Patients with Hepatocellular Carcinoma Is Associated with Poor Prognosis after Resection

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yu-Ling Chen ◽  
Chien-Hung Chen ◽  
Rey-Heng Hu ◽  
Ming-Chih Ho ◽  
Yung-Ming Jeng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Poor Prognosis ◽  
Characteristic Curve ◽  
Tumor Grade ◽  
Serum Levels ◽  
Tumor Stage ◽  
High Serum ◽  
Term Survival ◽  
Preoperative Serum

Serum levels of the tumor marker CA19-9 have been reported to be elevated in patients with hepatocellular carcinoma (HCC), but its clinicopathologic significance is still unknown. A cohort of 304 patients undergoing surgical resection for HCC and having preoperative CA19-9 data was enrolled in this study. Serum CA19-9 levels were correlated with clinicopathologic factors. Univariate and multivariate analyses were performed to determine the predictors of patient survival. On receiver operating characteristic curve analysis, the cut off value of CA19-9 was determined to be 27 U/mL. One hundred and six patients had preoperative CA19-9 values >27 U/mL. High serum CA19-9 levels did not correlate with patient age, sex, viral status,α-fetoprotein level, tumor size, tumor grade, tumor stage, multiplicity, and vascular invasion. Patients with elevated preoperative CA19-9 levels had lower 10-year survival than those without CA19-9 elevation. Multivariate analysis revealed that CA19-9 level, tumor grade, and tumor size are independent prognostic factors for long-term survival. In conclusion, a preoperative CA19-9 value >27 U/mL is associated with poor prognosis after resection for HCC.

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

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22043-e22043 ◽  
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.

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