GCNT3 regulated MUC13 to promote the development of hepatocellular carcinoma through the GSK3ß/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Extensive research is currently directed at identifying novel targets for its diagnosis and treatment. AIMS: We investigated the biological functions and clinical significance of mucin-type N-acetylglucosaminyltransferase 3 (GCNT3) in HCC. METHODS: Variations in the mRNA expression of GCNT3 were examined in normal and HCC tissues. Cell function assays and animal models characterized the effects of GCNT3 on the proliferation, invasion, and migration abilities of HCC cells. Western blot and immunofluorescence analyses were performed to explore further the specific mechanisms whereby GCNT3 affects HCC progression. RESULTS: There is a strong correlation between GCNT3 overexpression and tumor formation and metastasis in vivo and in vitro. GCNT3 acted as a regulator of the synthesis of mucin-type O-glycans by interacting with mucin 13 (MUC13) to regulate its expression levels, activating the GSK3ß/ß-catenin signaling pathway. The activation of GSK3ß/ß-catenin signaling by GCNT3 was mitigated by MUC13 knockdown. In clinical HCC specimens, GCNT3 expression was upregulated in HCC tissues compared to non-tumor tissues. Further, there was a significant correlation between high GCNT3 expression and poor patient survival. CONCLUSIONS: GCNT3 regulated tumor progression in HCC through the MUC13/GSK3-ß/ß-catenin signaling pathway.

FEN1 promotes cancer progression of cholangiocarcinoma by regulating the Wnt/ß-catenin signaling pathway.

PURPOSE: Cholangiocarcinoma (CHOL) comprises a cluster of highly heterogeneous malignant biliary tumors. Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. This study aimed to explore the biological functions and mechanisms of FEN1 in CHOL. METHODS: FEN1 expression was analyzed in tissues of patients with CHOL and FEN1 mutations. We observe the influence of FEN1 on cellular proliferation, migration, and invasion, as well as on DNA damage repair and glycolysis. Western blotting was performed to determine the regulatory mechanism of FEN1 in CHOL progression. RESULTS: FEN1 was highly expressed in the cancer tissues of CHOL patients. The high mutation rate of FEN1 in CHOL tissues was mainly due to the amplified repeats. FEN1 promotes the proliferation, migration, and invasion of HUCCT1 and QBC939 cells. In addition, FEN1 induced DNA damage repair and aerobic glycolysis in CHOL cells. FEN1 also promoted xenograft tumor growth in vivo. Moreover, we showed that FEN1 mediated the epithelial-mesenchymal transition (EMT) of CHOL. FEN1-mediated EMT was found to be transduced by the Wnt/ß-catenin signaling pathway. CONCLUSION: FEN1 was significantly overexpressed in CHOL tissues, and FEN1 regulates the progression of CHOL through the Wnt/ß-catenin signaling pathway.

Application value of Hisense computer-assisted surgery system three-dimensional reconstru-tion in precision treatment of pediatric liver tumors / 中华消化外科杂志

Objective:To investigate the application value of Hisense computer-assisted surgery system (CAS) three-dimensional reconstruction in the precision treatment of pediatric liver tumors.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 82 children with liver tumors who were admitted to Affiliated Hospital of Qingdao University from January 2013 to September 2021 were collected. There were 39 males and 43 females, aged 13(19)months. Children underwent upper abdominal dynamic enhanced computed tomography (CT) examination, and three-dimensional reconstruction was performed on CT images of arterial, equili-brium and venous phases with Hisense CAS. Surgical feasibility and scheme were evaluated and conducted based on the results of upper abdominal dynamic enhanced CT examination, and then revised according to three-dimensional reconstruction results of Hisense CAS. Observation indicators: (1) comparison of surgical scheme between two-dimensional enhanced CT images and three-dimensional reconstruction results of Hisense CAS; (2) intraoperative and postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination to detect postoperative compli-cations and residual liver compensation up to November 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were described as absolute numbers or percentages. Results:(1) Comparison of surgical scheme between two-dimensional CT images and three-dimensional reconstruction results of Hisense CAS. ① Based on the two-dimensional CT images, 42 cases of 82 children could undergo one-stage resection and 40 children could not. However, based on the three-dimensional reconstruction results of Hisense CAS, 48 cases of 82 children could undergo one-stage resection and 34 children could not. There were 6 children with one-stage resection feasibility based on the three-dimensional reconstruction results of Hisense CAS rather than the two-dimensional CT images. For the 34 children undergoing chemotherapy firstly, 31 cases had surgical feasibility after chemotherapy based on the two-dimensional CT images and 3 cases could not undergo surgery because of unapparent tumor regression or tumor surrounding impor-tant vessels. However, the 34 children had surgical feasibility after chemotherapy based on the three-dimensional reconstruction results of Hisense CAS. The revision rate of surgical feasibility was 11.0%(9/82) for the 82 children. ② Based on the two-dimensional CT images, 15 cases of 82 children underwent liver left lobectomy, 21 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 13 cases underwent extended left hemihepatectomy, 23 cases underwent extended right hemihepatectomy, 3 cases underwent segmental hepatectomy. However, based on the three-dimensional reconstruction results of Hisense CAS, 20 cases of 82 children underwent liver left lobectomy, 29 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 7 cases underwent extended left hemihepatectomy, 14 cases underwent extended right hemihepatectomy, 5 cases underwent segmental hepatectomy. The revision rate of surgical scheme was 36.6%(30/82) for the 82 children. (2) Intraoperative and postoperative situations. The operation time, volume of intraoperative blood loss, duration of postoperative hospital stay of the 82 children were (182±18)minutes, 20(10)mL, (10.2±1.9)days, respectively. (3) Follow-up. All the 82 children were followed up for 10 (range, 2?18)months. There was no obvious complication occurred to the 82 children after surgery, and the residual liver can satisfy the liver compensation of body. All the children survived well.Conclusion:Three-dimensional reconstruction of Hisense CAS is conducive to judging the surgical feasibility and formulation of accurate surgical plan of children with liver tumors.

Effect of Microvascular Invasion on the Prognosis in Hepatocellular Carcinoma and Analysis of Related Risk Factors: A Two-Center Study.

Objective: Microvascular invasion is considered to initiate intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). We aimed to analyze the effect of MVI on the prognosis in HCC and identify related risk factors for microvascular invasion (MVI). Methods: The clinical data of 553 HCC patients who underwent liver surgery at Qingdao University from January 2014 to December 2018 and 89 patients at Beijing Tsinghua Changgung Hospital treated between October 2014 and October 2019 were collected retrospectively. We explored the impact of MVI on the prognosis of patients with HCC using Kaplan-Meier analysis. We conducted logistic regression analysis to identify variables significantly related to MVI. Results: Pathological examination confirmed the presence of MVI in 265 patients (41.3%). Six factors independently correlated with MVI were incorporated into the multivariate logistic regression analysis: Edmondson-Steiner grade [odds ratio (OR) = 3.244, 95%CI: 2.243-4.692; p < 0.001], liver capsule invasion (OR = 1.755; 95%CI: 1.215-2.535; p = 0.003), bile duct tumor thrombi (OR = 20.926; 95%CI: 2.552-171.553; p = 0.005), α-fetoprotein (> 400 vs. < 400 ng/ml; OR = 1.530; 95%CI: 1.017-2.303; p = 0.041), tumor size (OR = 1.095; 95%CI: 1.027-1.166; p = 0.005), and neutrophil-lymphocyte ratio (OR = 1.086; 95%CI: 1.016-1.162; p = 0.015). The area under the receiver operating characteristic curve (AUC) was 0.743 (95%CI: 0.704-0.781; p < 0.001), indicating that our logistic regression model had significant clinical usefulness. Conclusions: We analyzed the effect of MVI on the prognosis in HCC and evaluated the risk factors for MVI, which could be helpful in making decisions regarding patients with a high risk of recurrence.

From adult to child: the development and prospect of precision liver surgery / 中华消化外科杂志

The concept of precision medicine has brought revolutionary changes to human health and medical treatment. In a broad sense, precision medicine is the application of advanced technologies such as gene sequencing, digital medicine, artificial intelligence, navigation technology, and biomedical engineering to clinical, basic, and public health medical research and practice. The purpose is to promote the continuous development of medical standards. The concept of precision surgery was first proposed by academician Dong Jiahong, who has played an exemplary role in the field of liver surgery for the oncology and other professional fields of surgery. The development and application of computer-assisted surgery systems have promoted the development of precision liver surgery. The digital liver three-dimensional reconstruction provides a new basis for liver vascular anatomy and liver segmentation, assists in the realization of individualized surgical planning, and the measurement of residual liver volume guarantees the safety of operation. The great progress of adult precision liver surgery has provided important help and guidance for the development of pediatric liver surgery. Compared with adults, pediatric liver tumors have their particularities. Pediatric liver tumors are often huge, complex in location, fast growing, and highly malignant. Most children do not have liver cirrhosis and are sensitive to chemotherapy. The liver volume changes greatly with age and weight. These differences determine that the treatment of liver tumors in children needs to adopt different models, and the diagnosis and treatment standards need to be improved. The authors elaborate on the topic of "from adult to child-the development and prospect of precision liver surgery" to promote precision surgery and comprehensive treatment of liver tumors.

Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells.

The programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing PDCD4 were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials.

The role and significance of digital reconstruction technique in liver segments based on portal vein structure / 中华外科杂志

Objective@#To study the segment of liver according to the large amount of three-dimensional(3D) reconstructive images of normal human livers and the vascular system, and to recognize the basic functional liver unit based on the anatomic features of the intrahepatic portal veins.@*Methods@#The enhanced CT primitive DICOM files of 1 260 normal human livers from different age groups who treated from October 2013 to February 2017 provided by 16 hospitals were analyzed using the computer-aided surgery system.The 3D liver and liver vascular system were reconstructed, and the digital liver 3D model was established.The vascular morphology, anatomical features, and anatomical distributions of intrahepatic portal veins were statistically analyzed.@*Results@#The digital liver model obtained from the 3D reconstruction of CAS displayed clear intrahepatic portal vein vessels of level four.Perform a digital liver segments study based on the analysis of level four vascular distribution areas.As the less anatomical variation of left hepatic portal vein, the liver was classified into four types of liver segmentation mainly based on right hepatic portal vein.Type A was similar to Couinaud or Cho′s segmentation, containing 8 segments(537 cases, 42.62%). Type B contained 9 segments as there are three ramifications of right-anterior portal vein(464 cases, 36.82%). The main difference for Type C was the variation of right-posterior portal vein which was sector shape(102 cases, 8.10%). Type D contained the cases with special portal vein variations, which needs three-dimensional simulation to design individualized liver resection plan(157 cases, 12.46%). These results showed that there was no significant difference in liver segmental typing between genders(χ2=2.179, P=0.536) and did not reveal any significant difference in liver segmental typing among the different age groups(χ2=0.357, P=0.949).@*Conclusions@#The 3D digital liver model can demonstrate the true 3D anatomical structures, and its spatial vascular variations.The observation of anatomic features, distribution areas of intrahepatic portal veins and individualized liver segmentation achieved via digital medical 3D visualization technology is of great value for understand the complexity of liver anatomy and to guide the precise hepatectomy.

A classification of types of hepatic vein based on data obtained from a computer-assisted surgery system and its clinical implications in liver surgery / 中华肝胆外科杂志

Objective To classify the types of hepatic vein and to measure their corresponding liver venous drainage volumes based on analysis of data obtained from a computer-assisted surgery system with an aim to provide an anatomical basis on individualized anatomical hepatectomy.Methods Thin-layer computed tomography (CT) imaging on 570 patients were reconstructed using the Hisense CAS.The types of hepatic vein were classified according to their anatomical variations.The margins of the hemilivers or sectors and their corresponding hepatic venous drainage volumes were displayed.Results The major hepatic veins were classified into three types:Type Ⅰ (270/570,47.4％),type Ⅱ (294/570,51.6％),and type Ⅲ (6/570,1.0％).The left hepatic vein (LHV) was classified as type Ⅰ in 190/570 (33.3％),type Ⅱ in 79/570 (13.9％),and type Ⅲ in 301/570 (52.8％).The middle hepatic vein (MHV) was classified as type Ⅰ in313/570 (54.9％),type Ⅱ in 174/570 (30.5％),and type Ⅲ in 83/570 (14.6％).The right hepatic vein (RHV) was classified as type Ⅰ in 456/570 (80.0％),type Ⅱ in 79/570 (13.9％),and type Ⅲ in 35/570 (6.1％).Type Ⅰ was further classified into four subtypes of A (26/456,5.7％),B (404/456,88.6％),C (20/456,4.4％),and D (6/456,1.3％).The LHV volume was (25.0± 6.6) ％,the MHV volume was (34.8 ± 9.5) ％ and the RHV volume was (25.1 ± 11.6) ％ in 63 patients with inferior right hepatic veins (IRHV).The IRHV and other branches volumes were (14.7 ± 7.4) ％.The RHV volume was (40.7 ± 8.6) ％ in 68 patients without IRHV.Conclusions Hepatic venous variations are complex.Significant differences existed in the hepatic venous drainage volumes.The Hisense CAS clearly delineated the relationship between the intrahepatic vascular structures and the liver carcinoma which hopefully can lead to improvement in the success rate of complex hepatectomy.

A classification of types of hepatic vein based on data obtained from a computer-assisted surgery system and its clinical implications in liver surgery / 中华肝胆外科杂志

Objective To classify the types of hepatic vein and to measure their corresponding liver venous drainage volumes based on analysis of data obtained from a computer-assisted surgery system with an aim to provide an anatomical basis on individualized anatomical hepatectomy.Methods Thin-layer computed tomography (CT) imaging on 570 patients were reconstructed using the Hisense CAS.The types of hepatic vein were classified according to their anatomical variations.The margins of the hemilivers or sectors and their corresponding hepatic venous drainage volumes were displayed.Results The major hepatic veins were classified into three types:Type Ⅰ (270/570,47.4％),type Ⅱ (294/570,51.6％),and type Ⅲ (6/570,1.0％).The left hepatic vein (LHV) was classified as type Ⅰ in 190/570 (33.3％),type Ⅱ in 79/570 (13.9％),and type Ⅲ in 301/570 (52.8％).The middle hepatic vein (MHV) was classified as type Ⅰ in313/570 (54.9％),type Ⅱ in 174/570 (30.5％),and type Ⅲ in 83/570 (14.6％).The right hepatic vein (RHV) was classified as type Ⅰ in 456/570 (80.0％),type Ⅱ in 79/570 (13.9％),and type Ⅲ in 35/570 (6.1％).Type Ⅰ was further classified into four subtypes of A (26/456,5.7％),B (404/456,88.6％),C (20/456,4.4％),and D (6/456,1.3％).The LHV volume was (25.0± 6.6) ％,the MHV volume was (34.8 ± 9.5) ％ and the RHV volume was (25.1 ± 11.6) ％ in 63 patients with inferior right hepatic veins (IRHV).The IRHV and other branches volumes were (14.7 ± 7.4) ％.The RHV volume was (40.7 ± 8.6) ％ in 68 patients without IRHV.Conclusions Hepatic venous variations are complex.Significant differences existed in the hepatic venous drainage volumes.The Hisense CAS clearly delineated the relationship between the intrahepatic vascular structures and the liver carcinoma which hopefully can lead to improvement in the success rate of complex hepatectomy.