scholarly journals Liprin-β1 is upregulated in human hepatocellular carcinoma and is associated with advanced tumor stage

2019 ◽  
Vol 71 (3) ◽  
pp. 469-474
Author(s):  
Xinying Li ◽  
Jingmei Li ◽  
Jiao Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Stage ◽  
Tumor Stage ◽  
Human Hepatocellular Carcinoma ◽  
Advanced Tumor Stage ◽  
Advanced Clinical Stage ◽  
Advanced Tumor ◽  
Elevated Expression ◽  
Clinicopathological Significance ◽  
Liver Tissues

Liprin-?1 is one of the broadly-expressed liprin family members. Dysregulation of liprin-?1 has been implicated in several types of human cancers. However, the expression of liprin-?1 and its clinicopathological significance in human hepatocellular carcinoma (HCC) remains elusive. We evaluated the protein expression of liprin-?1 in HCC and non-tumor liver tissues by immunohistochemistry, and investigated the relationship between liprin-?1 expression and the clinicopathological attributes of HCC. We found that liprin-?1 expression was significantly higher in HCC than in non-tumor liver tissues. Further analysis showed that higher levels of liprin-?1 in HCC were significantly associated with the advanced clinical stage. Interestingly, liprin-?1 was not detected in cholangiocellular carcinoma specimens. These findings suggest that an elevated expression of liprin-?1 may be involved in HCC progression, providing the rationale that upregulation of liprin-?1 may serve as a novel biomarker for human HCC.

scholarly journals Type III TGF-β Receptor Down-Regulation Promoted Tumor Progression via Complement Component C5a Induction in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1503
Author(s):  
Oscar Wai Ho Yeung ◽  
Xiang Qi ◽  
Li Pang ◽  
Hui Liu ◽  
Kevin Tak Pan Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Tumor Stage ◽  
Complement Component ◽  
Soluble Form ◽  
Advanced Tumor Stage ◽  
Down Regulation ◽  
Type Iii ◽  
Advanced Tumor ◽  
Β Receptor

Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased complement component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting complement C5a.

scholarly journals Prognostic and clinicopathological significance of neutrophil-to-lymphocyte ratio in patients with oral cancer

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yun Yang ◽  
Rongxun Liu ◽  
Feng Ren ◽  
Rui Guo ◽  
Pengfei Zhang
Keyword(s):  
Oral Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Tumor Stage ◽  
Neutrophil To Lymphocyte Ratio ◽  
Advanced Tumor Stage ◽  
Lymphocyte Ratio ◽  
Advanced Tumor ◽  
Oral Cancer Patients ◽  
Clinicopathological Significance

Objectives: Many studies have examined the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in oral cancer; however, the results are contradictory. We, therefore, conducted a meta-analysis aiming to clarify the prognostic value of the NLR in oral cancer patients. Methods: A literature search was conducted in the PubMed, Web of Science, and Embase databases. Stata version 12.0 was used for statistical analysis. Results: A total of 14 studies with 3216 patients were finally included. The results indicated that a high NLR was significantly associated with worse DFS (n=10, HR = 1.73, 95% confidence interval [CI] = 1.44–2.07, P<0.001). Similar results were observed for overall survival (OS) (n=9, HR = 1.61, 95% CI = 1.39–1.86, P<0.001). Moreover, a high NLR was also correlated with lymph node metastasis (n=7, odds ratio [OR] = 1.62, 95% CI = 1.32–1.98, P<0.001), advanced tumor stage (n=7, OR = 2.63, 95% CI = 2.12–3.25, P<0.001), T stage (n=6, OR = 3.22, 95% CI = 2.59–4.01, P<0.001), tumor differentiation (n=5, OR = 1.48, 95% CI = 1.03–2.11, P=0.033), and perineural invasion (n=4, OR = 1.83, 95% CI = 1.4–2.39, P<0.001). However, an elevated NLR was not correlated with gender. Conclusion: This meta-analysis showed that the NLR might be a potential independent prognostic factor in patients with oral cancer.

Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma

2000 ◽  
Vol 89 (4) ◽  
pp. 350-355 ◽  
Author(s):  
Andrea Tannapfel ◽  
Dorothee Grund ◽  
Alexander Katalinic ◽  
Dirk Uhlmann ◽  
Ferdinand K�ckerling ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Advanced Tumor

scholarly journals The interplay of UBE2T and Mule in regulating Wnt/β-catenin activation to promote hepatocellular carcinoma progression

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Nicole Pui Yu Ho ◽  
Carmen Oi Ning Leung ◽  
Tin Lok Wong ◽  
Eunice Yuen Ting Lau ◽  
Martina Mang Leng Lei ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Stage ◽  
Attractive Potential ◽  
Advanced Tumor Stage ◽  
E3 Ligases ◽  
Related Data ◽  
Protein Levels ◽  
Advanced Tumor ◽  
Ubiquitin Conjugating Enzyme

AbstractEmerging evidence indicates the role of cancer stem cells (CSCs) in tumor relapse and therapeutic resistance in patients with hepatocellular carcinoma (HCC). To identify novel targets against liver CSCs, an integrative analysis of publicly available datasets involving HCC clinical and stemness-related data was employed to select genes that play crucial roles in HCC via regulation of liver CSCs. We revealed an enrichment of an interstrand cross-link repair pathway, in which ubiquitin-conjugating enzyme E2 T (UBE2T) was the most significantly upregulated. Consistently, our data showed that UBE2T was upregulated in enriched liver CSC populations. Clinically, UBE2T overexpression in HCC was further confirmed at mRNA and protein levels and was correlated with advanced tumor stage and poor patient survival. UBE2T was found to be critically involved in the regulation of liver CSCs, as evidenced by increases in self-renewal, drug resistance, tumorigenicity, and metastasis abilities. Mule, an E3 ubiquitin ligase, was identified to be the direct protein binding partner of UBE2T. Rather than the canonical role of acting as a mediator to transfer ubiquitin to E3 ligases, UBE2T is surprisingly able to physically bind and regulate the protein expression of Mule via ubiquitination. Mule was found to directly degrade β-catenin protein, and UBE2T was found to mediate liver CSC functions through direct regulation of Mule-mediated β-catenin degradation; this effect was abolished when the E2 activity of UBE2T was impaired. In conclusion, we revealed a novel UBE2T/Mule/β-catenin signaling cascade that is involved in the regulation of liver CSCs, which provides an attractive potential therapeutic target for HCC.

scholarly journals The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

2021 ◽  
Author(s):  
Marica Meroni ◽  
Miriam Longo ◽  
Erika Paolini ◽  
Anna Alisi ◽  
Luca Miele ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Tumor Stage ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver ◽  
Advanced Tumor

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A&gt;G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p&lt;0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p&lt;0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p&lt;0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p&lt;0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p&lt;0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p&lt;0.05). Conclusions: In sum, the rs599839 A&gt;G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

scholarly journals Artificial Intelligent Multi-Modal Point-of-Care System for Predicting Response of Transarterial Chemoembolization in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhongqi Sun ◽  
Zhongxing Shi ◽  
Yanjie Xin ◽  
Sheng Zhao ◽  
Hao Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Large Scale ◽  
Point Of Care ◽  
Tumor Stage ◽  
Interventional Therapy ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Point Of Care System ◽  
Care System

Hepatocellular carcinoma (HCC) ranks the second most lethal tumor globally and is the fourth leading cause of cancer-related death worldwide. Unfortunately, HCC is commonly at intermediate tumor stage or advanced tumor stage, in which only some palliative treatment can be used to offer a limited overall survival. Due to the high heterogeneity of the genetic, molecular, and histological levels, HCC makes the prediction of preoperative transarterial chemoembolization (TACE) efficacy and the development of personalized regimens challenging. In this study, a new multi-modal point-of-care system is employed to predict the response of TACE in HCC by a concept of integrating multi-modal large-scale data of clinical index and computed tomography (CT) images. This multi-modal point-of-care predicting system opens new possibilities for predicting the response of TACE treatment and can help clinicians select the optimal patients with HCC who can benefit from the interventional therapy.

scholarly journals Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma

2018 ◽  
Vol 45 (3) ◽  
pp. 1097-1107 ◽  
Author(s):  
Yufu Tang ◽  
Ruoyu Wang ◽  
Yibing Zhang ◽  
Shenhui Lin ◽  
Na Qiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hazard Analysis ◽  
Survival Rates ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Cox Proportional Hazard ◽  
Advanced Tumor ◽  
Cumulative Recurrence Rate ◽  
Combined Detection

Background/Aims: 14-3-3ζ is involved in the regulation of PI3K/Akt pathway which is closely associated with carcinogenesis. However, the clinical significance of combined detection of 14-3-3ζ and p-Akt in hepatocellular carcinoma (HCC) remains unclear. Methods: Two-hundred pairs of HCC and adjacent liver specimens were subjected to tissue microarray. The association of 14-3-3ζ and p-Akt levels with the postoperative survival and recurrence in HCC patients was analyzed with univariate and multivariate methods. Moreover, the effects of 14-3-3ζ overexpression on the growth of HCC and the expressions of p-Akt and HIF-1α were assessed in a xenograft mouse model. Results: Elevated levels of 14-3-3ζ and p-Akt were detected in HCC and a positive correlation between the levels of 14-3-3ζ and p-Akt was verified. HCC patients with satellite nodules, microvascular invasion, portal vein tumor thrombosis, poor tumor differentiation and an advanced tumor stage tended to have higher levels of 14-3-3ζ and p-Akt. In addition, the postoperative 3-, 5-, and 7-year overall survival rates in HCC patients with 14-3-3ζhigh and p-Akthigh were significantly lower compared with those with 14-3-3ζlow and p-Aktlow, and the cumulative recurrence rate in HCC patients with 14-3-3ζhigh and p-Akthigh was significantly higher than that in those with 14-3-3ζlow and p-Aktlow. The multivariate Cox proportional hazard analysis indicated that concomitant upregulation of 14-3-3ζ and p-Akt was an independent factor that predicted poor survival and high recurrence in HCC patients. Furthermore, animal experiment showed that overexpression of 14-3-3ζ accelerated the growth of HCC xenograft tumors and induced the expressions of p-Akt and HIF-1α in vivo. Conclusion: Co-upregulation of 14-3-3ζ and p-Akt predicts poor prognosis in patients with HCC, and 14-3-3ζ-induced activation of the Akt signaling pathway contributes to HCC progression.

scholarly journals The rs599839 A>G Variant Disentangles Cardiovascular Risk and Hepatocellular Carcinoma in NAFLD Patients

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1783
Author(s):  
Marica Meroni ◽  
Miriam Longo ◽  
Erika Paolini ◽  
Anna Alisi ◽  
Luca Miele ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Tumor Stage ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver ◽  
Advanced Tumor

Background and Aims: Dyslipidemia and cardiovascular diseases (CVD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 gene cluster, has been associated CVD, but its impact on metabolic traits and on the severity liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 had HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC), and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n = 125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p < 0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The minor G allele was associated with higher risk of HCC, independently of fibrosis severity (odds ratio (OR): 5.62; 95% c.i. 1.77–17.84, p = 0.003), poor prognosis and advanced tumor stage (p < 0.05) in the overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p < 0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p < 0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p < 0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p < 0.05). Conclusions: In sum, the rs599839 A>G variant is associated with protection against dyslipidemia and CVD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively.

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