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

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.

Download Full-text

TINCR expression is associated with unfavorable prognosis in patients with hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20170301 ◽

2017 ◽

Vol 37 (4) ◽

Cited By ~ 21

Author(s):

Feng Tian ◽

Jian Xu ◽

Fangxi Xue ◽

Encui Guan ◽

Xiaoguang Xu

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Disease Free Survival ◽

Prognostic Indicator ◽

Clinicopathological Characteristics ◽

Cox Regression Analysis ◽

Functional Roles ◽

Kaplan Meier ◽

Promising Target ◽

Differentiation Status

Emerging evidence are accumulating that long noncoding RNAs (lncRNAs) have recently been identified to participate in various cellular processes. Terminal differentiation induced ncRNA (TINCR) is a newly identified lncRNA with its functional roles not fully elucidated in human malignancy. The current study aims to identify the clinical significance of TINCR in prognosis and malignant progression of hepatocellular carcinoma (HCC). TINCR expression in HCC specimens at various stages of tumorigenesis were measured by quantitative real-time RT PCR (qRT-PCR). The matched para-carcinoma tissues were used as controls. The associations of TINCR with clinicopathological characteristics, disease-free survival (DFS) and overall survival (OS) of patients were further evaluated. Results revealed that high TINCR expression was significantly correlated with tumor size (P=0.005), tumor differentiation status (P=0.017), TNM stage (P=0.010), and vascular invasion (P=0.004). Moreover, Kaplan–Meier analysis demonstrated that TINCR was correlated to both DFS and OS in HCC cohorts. Patients with high TINCR expression tended to have worse prognosis. Multivariate Cox regression analysis indicated that TINCR was an independent poor prognostic indicator for DFS (HR =1.32, 95% CI: 1.00–1.57, P=0.000) and OS (HR =1.57, 95% CI: 1.30–1.86, P=0.004) in HCC. TINCR was demonstrated as a direct target of miR-137 and miR-133a, and was suppressed by miR-137/miR-133a. These results provide the first evidence that the expression of TINCR in HCC may play an oncogenic role in HCC differentiation, invasion, and metastasis. miR-137/miR-133a-TINCR pathway may serve as a promising target for tumor recurrence and prognosis of patients with HCC.

Download Full-text

Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽

10.1515/med-2021-0221 ◽

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.

Download Full-text

Predictive Value of F-SIRI in Prognosis of Patients with Hepatocellular Carcinoma after Radical Hepatectomy

10.21203/rs.3.rs-651278/v1 ◽

2021 ◽

Author(s):

hu panyi ◽

Yongwei Zhang ◽

yeben qian

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Predictive Value ◽

Cox Regression ◽

Clinicopathological Characteristics ◽

Tumor Diameter ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

High Level ◽

The Relationship

Abstract Background: Objective to evaluate the predictive value of preoperative fibrinogen and systemic inflammatory response index (F-SIRI) in the prognosis of patients with hepatocellular carcinoma after radical hepatectomy. Methods: the clinical data of 298 patients with hepatocellular carcinoma who underwent surgery and confirmed by postoperative pathology in our hospital from January 2015 to December 2017 were retrospectively analyzed. The F-SIRI score was calculated according to FIB and SIRI data of peripheral blood. The relationship between F-SIRI score and clinicopathological characteristics was analyzed. The survival analysis was performed by Kaplan Meier method, Cox regression analysis was used to analyze the prognostic factors. Results: preoperative F-SIRI score was correlated with tumor diameter, FIB and SIRI (P<0.05), but not with age, gender, TNM stage and other clinical features (P>0.05). There were significant differences in the 5-year DFS rate and OS rate among patients with different preoperative F-SIRI scores(P<0.05); Cox regression analysis showed that preoperative tumor diameter, alpha fetoprotein level and F-SIRI score were independent predictors of DFS in patients with HCC (P< 0.05), while preoperative tumor diameter, ALB and F-SIRI score as independent predictors of OS (P<0.05). Conclusion: preoperative F-SIRI is an independent prognostic factor in patients with HCC after radical hepatectomy, with poor prognosis in patients with high level of F-SIRI.

Download Full-text

Role of Autophagy in the Prognosis of Combined Hepatocellular Carcinoma and Cholangiocarcinoma after Surgical Resection

10.21203/rs.3.rs-153575/v1 ◽

2021 ◽

Author(s):

Daw-Shyong Perng ◽

Hung-Yu Lin ◽

Paul Morgan ◽

Tsung-Chin Wu ◽

Chao-Ming Hung ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Clinical Prognosis ◽

Free Survival ◽

Cox Regression Analysis ◽

Tumor Tissues ◽

Related Proteins

Abstract Background: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7% and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2% and 74.6% in high LC3 expression patients and 0% and 0% in those with low LC3 expression. Conclusion: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Download Full-text

Role of autophagy-related protein in the prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgical resection

BMC Cancer ◽

10.1186/s12885-021-08553-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Daw-Shyong Perng ◽

Chao-Ming Hung ◽

Hung-Yu Lin ◽

Paul Morgan ◽

Yao-Chun Hsu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Clinical Prognosis ◽

Free Survival ◽

Cox Regression Analysis ◽

Tumor Tissues ◽

Related Proteins

Abstract Background Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. Conclusion High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Download Full-text

Expression and clinical significance of miR-3615 in hepatocellular carcinoma

Journal of International Medical Research ◽

10.1177/0300060520981547 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098154

Author(s):

Xin Yuan ◽

Yize Zhang ◽

Zujiang Yu

Keyword(s):

Hepatocellular Carcinoma ◽

Survival Curve ◽

Clinicopathological Characteristics ◽

The Cancer Genome Atlas ◽

Prognostic Information ◽

Ki 67 ◽

Tissue Samples ◽

Expression Levels ◽

Kaplan Meier ◽

Serum Alpha Fetoprotein

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.

Download Full-text

Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

10.21203/rs.3.rs-1070685/v1 ◽

2021 ◽

Author(s):

Xinxin Chen ◽

Wenxia Qiu ◽

Xuekun Xie ◽

Zefeng Chen ◽

Zhiwei Han ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Resection ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Tumor Diameter ◽

Cox Regression Analysis ◽

Tumor Capsule ◽

Calibration Curves ◽

Solitary Hepatocellular Carcinoma

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

Download Full-text

Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2019/9691067 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Hai-Ge Zhang ◽

Ping Yang ◽

Tao Jiang ◽

Jian-Ying Zhang ◽

Xue-Juan Jin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

External Beam Radiation ◽

Rank Test ◽

Beam Radiation ◽

Kaplan Meier ◽

Target Volumes ◽

The Relationship

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.

Download Full-text

The Lung Adenocarcinoma Microenvironment Mining and Its Prognostic Merit

Technology in Cancer Research & Treatment ◽

10.1177/1533033820977547 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097754

Author(s):

Rongchang Zhao ◽

Dan Ding ◽

Wenyan Yu ◽

Chunrong Zhu ◽

Yan Ding

Keyword(s):

Lung Adenocarcinoma ◽

Cox Regression ◽

Clinicopathological Characteristics ◽

Survival Prognosis ◽

Kaplan Meier ◽

Relationship Of ◽

Immune Score ◽

The Relationship ◽

Kaplan Meier Plotter ◽

Tumor Topography

Background: As a common pathological type of lung cancer, lung adenocarcinoma (LUAD) is mainly treated by surgery, chemotherapy, targeted therapy and radiotherapy. Although a relatively mature treatment system has been established, there are few studies on the microenvironment of LUAD. Material and Methods: The immune and stromal scores of patients from the LUAD cohort in the TCGA database were obtained by using ESTIMATE. The relationship of immune and stromal scores with the clinicopathological characteristics and overall survival of LUAD patients was assessed by R. GO, KEGG and Cox regression analyses were employed to analyze intersecting genes and to identify reliable prognostic markers. The identified genes were also analyzed in the GEPIA database to assess their correlations with survival, and these relationships were verified with the Kaplan-Meier Plotter database. Results: The immune score was related to the survival time and tumor topography of LUAD patients. There was a significant correlation between stromal score and tumor metastasis. Through multivariate analysis, stage (HR = 1.640, 95% CI = 1.019-2.642, P = 0.042) and risk score (HR = 1.036, 95% CI = 1.026-1.046, P < 0.001). The genes (ARHGAP15, BTLA, CASS4, CLECL1, FAM129C, STAP1, TESPA1, and S100P) showed credible prognostic value in LUAD patients in TCGA through GEPIA database online analysis and verification in the Kaplan-Meier plotter database. Conclusions: In the microenvironment of lung adenocarcinoma, the differentially expressed genes screened by immune score and stromal score have certain value in evaluating the survival/prognosis of patients, as well as the invasion and progression of tumors.

Download Full-text

Crosstalk between Activated and Inactivated c-Src in Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2011/946295 ◽

2011 ◽

Vol 30 (6) ◽

pp. 325-333 ◽

Cited By ~ 8

Author(s):

Mei-Lin Chen ◽

Chee-Yin Chai ◽

Kun-Tu Yeh ◽

Shen-Nien Wang ◽

Chia-Jung Tsai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Rate ◽

Cox Regression ◽

Patient Survival ◽

Survival Curve ◽

Clinicopathological Characteristics ◽

Active State ◽

Overall Survival Rate ◽

Independent Prognostic Marker

C-Src activity is regulated by tyrosine phosphorylation at two distinct sites, Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these sites in human cancers are not well defined. This study aims to determine whether the alterations and crosstalk of these two sites may contribute to hepatocellular carcinoma (HCC). Specimens from 85 patients who had undergone curative hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p-Tyr527-Src, as well as the non-phosphorylated status for each site, were determined using immunohistochemistry and statistically correlated with clinicopathological characteristics and overall survival rate. The active state of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade (P= 0.062) but inversely correlated with vascular invasion (P= 0.071). Its non-phosphorylated status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade (P= 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased in male patients but increased HCV-infected patients (P= 0.044 and 0.033). The Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and decreased non-p-Tyr527-c-Src expression were associated with a poor patient survival rate (P= 0.004 and 0.025). Interestingly, the expression of non-p-Tyr416-c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions (P= 0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and non-p-Tyr527-c-Src expression had a prolonged overall survival rate (P= 0.030). A multivariable COX regression model showed that p-Tyr416-c-Src expression was an effective predictor for patient survival in HCC [OR = 3.78, 95%CI = 1.46–9.76;P= 0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may serve as an independent prognostic marker of patient survival in HCC. Relative levels of other phosphorylated or non-phosphorylated c-Src kinases may also present different statuses during HCC development and require further investigation.

Download Full-text