Crosstalk between Activated and Inactivated c-Src in Hepatocellular Carcinoma

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.

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Prediction of Overall Survival Rate in Patients With Hepatocellular Carcinoma Using an Integrated Model Based on Autophagy Gene Marker

Frontiers in Genetics ◽

10.3389/fgene.2021.647309 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shuaiqun Wang ◽

Dalu Yang ◽

Wei Kong

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Rate ◽

Clinical Data ◽

Cox Regression ◽

Cox Model ◽

Pathway Enrichment Analysis ◽

Gene Marker ◽

Overall Survival Rate ◽

Cox Regression Analysis

The autophagy cell, which can inhibit the formation of tumor in the early stage and can promote the development of tumor in the late stage, plays an important role in the development of tumor. Therefore, it has potential significance to explore the influence of autophagy-related genes (AAGs) on the prognosis of hepatocellular carcinoma (HCC). The differentially expressed AAGs are selected from HCC gene expression profile data and clinical data downloaded from the TCGA database, and human autophagy database (HADB). The role of AAGs in HCC is elucidated by GO functional annotation and KEGG pathway enrichment analysis. Combining with clinical data, we selected age, gender, grade, stage, T state, M state, and N state as Cox model indexes to construct the multivariate Cox model and survival curve of Kaplan Meier (KM) was drawn to estimate patients’ survival between high- and low-risk groups. Through an ROC curve drawn by univariate and multivariate Cox regression analysis, we found that seven genes with high expression levels, including HSP90AB1, SQSTM1, RHEB, HDAC1, ATIC, HSPB8, and BIRC5 were associated with poor prognosis of HCC patients. Then the ICGC database is used to verify the reliability and robustness of the model. Therefore, the prognosis model of HCC constructed by autophagy genes might effectively predict the overall survival rate and help to find the best personalized targeted therapy of patients with HCC, which can provide better prognosis for 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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Treatments for the early stage Hepatocellular Carcinoma: Laparoscopic Liver Resection or Percutaneous Radiofrequency, How to make the decision?

Liver Cancer ◽

10.1159/000521136 ◽

2021 ◽

Author(s):

Jinli Zheng ◽

Wei Xie ◽

Yunfeng Zhu ◽

Li Jiang

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Rate ◽

Liver Resection ◽

Complication Rate ◽

Early Stage ◽

Line Treatment ◽

Overall Survival Rate ◽

First Line ◽

First Line Treatment

Hepatectomy is still as the first-line treatment for the early stage HCC, but the complication rate is higher than p-RFA and the overall survival rate is comparable in these two treatments. Therefore, the patients with small single nodular HCCs could get more benefit from p-RFA, and we need to do further research about p-RFA.

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Decreased Expression of KPNA2 in Hepatocellular Carcinoma Infers Favorable Prognosis and High Immune Infiltrating Level

10.21203/rs.3.rs-691618/v1 ◽

2021 ◽

Author(s):

kangming zhu ◽

yvndi zhang ◽

hui yvan ◽

jing li

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Logistic Regression ◽

Survival Rate ◽

Western Blotting ◽

Good Prognosis ◽

Overall Survival Rate ◽

Pathological Stage ◽

Down Regulation ◽

Immune Infiltration

Abstract BackgroundLiver hepatocellular carcinoma (LIHC) is an important pathological type of liver cancer. The immune infiltration of the tumor microenvironment is negatively correlated with the overall survival rate of LIHC. At present , the role and molecular mechanism of KPNA2 in LIHC have not been elucidated, and the prognostic correlation between the two and the immune infiltration of LIHC are still unclear. Our study evaluated the role of KPNA2 in LIHC through TCGA data.MethodGene expression profiling interactive analysis (GEPIA) is used to analyze the expression of KPNA2 in LIHC. We evaluated the impact of KPNA2 on the survival of LIHC patients through the survival module. Then, We downloaded the LIHC data set from TCGA. Logistic regression was used to analyze the correlation between clinical information and KPNA2 expression. Cox regression analysis was used to analyze the clinicopathological characteristics related to the overall survival rate of TCGA patients. In addition, we used the "correlation" modules of CIBERSORT and GEPIA to explore the correlation between KPNA2 and cancer immune infiltrate. Western blotting was used to detect the expression of KPNA2.ResultUsing logistic regression for univariate analysis, increased KPNA2 expression was significantly correlated with pathological stage, tumor status, and lymph node status. In addition, multivariate analysis showed that down-regulation of KPNA2 expression, negative pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, CIBERSORT analysis was used to establish a negative correlation between the up-regulated expression of KPNA2 and the level of immune infiltration of B cells, NK cells, mast cells, and T cells. In addition, we confirmed this in the "Association" module of GEPIA. The expression of KPNA2 in LIHC tissues was significantly lower than that in adjacent normal tissues by western blotting.ConclusionThe down-regulation of KPNA2 expression is associated with a good prognosis and an increase in the proportion of immune cells in LIHC. These conclusions indicate that KPNA2 is related to the level of immune infiltration of LIHC and can be used as a potential prognostic biomarker of LIHC and a potential target for clinical tumor treatment.

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Clinical factors affecting prognosis of limb osteosarcoma in China: a multicenter retrospective analysis

Journal of International Medical Research ◽

10.1177/0300060520920053 ◽

2020 ◽

Vol 48 (8) ◽

pp. 030006052093085

Author(s):

Jia Han ◽

Yiyang Yu ◽

Sujia Wu ◽

Zhen Wang ◽

Weibin Zhang ◽

...

Keyword(s):

Overall Survival ◽

Survival Rate ◽

Cox Regression ◽

Survival Rates ◽

Treatment Method ◽

Overall Survival Rate ◽

Clinical Factors ◽

Standard Chemotherapy ◽

Factors Affecting ◽

Cox Regression Analysis

Objective This study was performed to explore the relationship between various clinical factors and the prognosis of limb osteosarcoma. Methods We retrospectively analyzed the clinical data of 336 patients with limb osteosarcoma treated from June 2000 to August 2016 at 7 Chinese cancer centers. Data on the patients’ clinical condition, treatment method, complications, recurrences, metastasis, and prognosis were collected and analyzed. Kaplan–Meier analysis and Cox regression models were used to analyze the data. Results The patients comprised 204 males and 132 females ranging in age from 6 to 74 years (average, 21.1 years). The overall 3- and 5-year survival rates were 65.0% and 55.0%, respectively. The 5-year overall survival rate was 64.0% with standard chemotherapy and 45.6% with non-standard chemotherapy. Cox regression analysis demonstrated that standard chemotherapy, surgery, recurrence, and metastasis were independent factors associated with the prognosis of limb osteosarcoma. Conclusion The survival of patients with limb osteosarcoma can be significantly improved by combining standard chemotherapy and surgery. The overall survival rate can also be improved by adding methotrexate to doxorubicin–cisplatin–ifosfamide triple chemotherapy.

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PS02.094: EVALUATION OF ADDITIONAL TREATMENT AFTER NON-CURATIVE ENDOSCOPIC SUBMUCOSAL RESECTION FOR ESOPHAGEAL CANCER

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps02.094 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 147-148

Author(s):

Shinji Ohki ◽

Takuto Hikichi ◽

Leo Yamada ◽

Daisuke Ujiie ◽

Azuma Nirei ◽

...

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Survival Rate ◽

Curative Resection ◽

Clinicopathological Characteristics ◽

Additional Treatment ◽

Overall Survival Rate ◽

Superficial Esophageal Cancer ◽

Node Metastasis ◽

Submucosal Resection

Abstract Background Recently, endoscopic submucosal dissection (ESD) has been used as a less invasive treatment for superficial esophageal cancer. Additional treatment is often required after non-curative resection to prevent local recurrence and lymph node metastasis. Here, we present the outcomes of various additional treatments for patients with superficial esophageal cancer who underwent ESD. Methods Between 2006 and 2017, we performed ESD in 179 patients (210 lesions) with superficial esophageal cancer and 44 cases resulted in the non-curative resection diagnosed by the pathological examination. Among them, 29 patients received additional treatment, whereas 15 patients with no additional treatment were followed up. Additional treatment included esophagectomy (8 patients), chemoradiotherapy (15 patients), ablation using argon plasma coagulation (4 patients), and chemotherapy alone (2 patients). We examined the clinicopathological characteristics and prognosis of patients in the additional esophagectomy group (S group) and chemoradiotherapy group (CRT group). Results Twenty-three patients with pT1a-MM, pT1b, lymphatic invasion, venous invasion, and positive resection margins (both horizontal and vertical) were divided into two treatment groups. Clinicopathological characteristics of patients in the S and CRT groups were not significantly different. Pathological findings after additional esophagectomy showed one residual tumor and one lymph node metastasis. There were no recurrences in the two groups. There was no statistically significant difference in the 5-year overall survival rate between the S group (87.5%) and the CRT group (93.3%). One patient from the S group died due to respiratory pneumonia, and one patient died due to radiation pneumonia. However, five out of the 15 (33.3%) patients who were followed up with no additional treatment developed recurrence. The 5-year overall survival rate was 40.4%, which was not significantly different from that in the additional treatment group. However, the 5-year relapse-free survival rate (30%) was significantly different from that in the additional treatment group (P > 0.05). Conclusion Additional treatment is essential after non-curative endoscopic submucosal resection for esophageal cancer. Additional esophagectomy and chemoradiotherapy were both safe and effective in this cohort. Disclosure All authors have declared no conflicts of interest.

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Nomograms Predicting Long-Term Overall Survival and Cancer-Specific Survival in Metastatic Hepatocellular Carcinoma Patients

10.21203/rs.3.rs-31444/v1 ◽

2020 ◽

Author(s):

Chi Cui ◽

Yaru Duan ◽

Rui Li ◽

Hua Ye ◽

Peng Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

Training Group ◽

Clinicopathological Characteristics ◽

Validation Group ◽

Cancer Specific Survival ◽

Term Survival ◽

Metastatic Hepatocellular Carcinoma

Abstract Background This study aims to evaluate the clinicopathological characteristics of metastatic hepatocellular carcinoma (HCC) patients and develop nomograms to predict their long-term overall survival (OS) and cancer-specific survival (CSS). Methods Information on metastatic HCC from 2010 to 2015 was retrieved from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. The metastatic HCC patients were divided into a long-term survival (LTS) group and a short-term survival (STS) group with 1 year selected as the cut-off value. Then, we compared the demographic and clinicopathological features between the two groups. Next, all patients were randomly divided into a training group and validation group at a 7:3 ratio. Univariate and multivariate Cox regression analyses were used to identify potential predictors for OS and CSS in the training group, and nomograms of OS and CSS were established. These predictive models were further validated in the validation group. Results A total of 2163 patients were included in the current study according to the inclusion and exclusion criteria. Patients with characteristics including lower T stage and N stage; treatment with surgery, radiation or chemotherapy; no lung metastasis; and AFP negative status showed better survival. The concordance index (C-index) of the OS nomogram was 0.72 based on 9 variables. The C-index of the CSS nomogram was 0.71 based on 8 variables. Conclusions These nomograms may help clinicians make better treatment recommendations for metastatic HCC patients.

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EYA4 could be an indicator signifying colorectal cancer sufferers' prognoses

10.21203/rs.3.rs-46920/v1 ◽

2020 ◽

Author(s):

Yang Yan ◽

Xiaohui Du ◽

Shaoyou Xia ◽

Songyan Li ◽

Da Teng ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

Survival Curve ◽

Mrna Level ◽

Clinicopathological Characteristics ◽

Rank Test ◽

Normal Tissues ◽

Log Rank Test ◽

Low Expression

Abstract Background Eyes absent 4 (EYA4) is involved in various biological processes. The aim of this study was to investigate the expression of EYA4 and its prognostic value in colorectal cancer (CRC). Methods The mRNA level of EYA4 in diseased tissues and adjacent normal tissues of CRC patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The association between EYA4 expression and clinicopathological characteristics was analyzed by χ2 test. Kaplan-Meier analysis with log rank test was performed to evaluate the effects of EYA4 expression on overall survival of CRC patients. Cox regression model was applied for prognosis analysis in CRC. Results The mRNA level of EYA4 was significantly decreased in CRC tissues compared with that in the adjacent normal tissue (P < 0.01). And its expression was affected by DUKE stage (P = 0.034), differentiation (P = 0.027) and vascular invasion (P = 0.037). Survival curve showed that patients with low expression of EYA4 had a significantly shorter overall survival than those with high expression (log rank test, P = 0.008). Low expression of EYA4 (HR = 1.989, 95%CI = 1.090-3.62902, P = 0.025) was an independent biomarker for poor prognosis in CRC patients. Conclusion EYA4 expression is decreased in CRC patients and negatively correlated with aggressive tumor progression. EYA4 may be a potential prognostic biomarker for CRC.

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Twenty Years of Renal Transplantation in Children

PEDIATRICS ◽

10.1542/peds.77.4.465 ◽

1986 ◽

Vol 77 (4) ◽

pp. 465-470

Author(s):

Donald Potter ◽

Nicholas Feduska ◽

Juliet Melzer ◽

Marvin Garovoy ◽

Susan Hopper ◽

...

Keyword(s):

Overall Survival ◽

Renal Transplantation ◽

Survival Rate ◽

Living Donor ◽

Patient Survival ◽

Survival Rates ◽

Overall Survival Rate ◽

Creatinine Concentration ◽

The Mean ◽

Cadaver Donor

Two-hundred three children 1 to 16 years of age received kidney transplants during a 20-year period, 100 from living donors and 103 from cadaver donors. The overall survival rate was 79%. Actuarial patient and kidney survival rates at 15 years were 79% and 52%, respectively, for recipients of living donor kidneys and 57% and 19%, respectively, for recipients of cadaver donor kidneys. One of two children who received transplants in 1964 was alive 20½ years later. Twenty-nine children had kidneys that had functioned more than 10 years; their mean serum creatinine concentration was 1.7 mg/dL and 24 were fully rehabilitated. Eighteen were more than 2 SD below the mean height of normal chidren, however. Comparison of survival rates during successive 5-year intervals showed significant improvement in patient survival during the 20-year period and smaller improvements in kidney survival after 1979. Patient survival after living donor transplants during the last 10 years was 100%, and kidney survival during the last 5 years was 92%. Improvement was attributed to the effect of experience, as well as to changes in immunosuppressive therapy in 1972 and the introduction of donor-specific transfusions in 1978.

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