Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary neoplasm, which originates from the bile ducts proximal to the second-order division. ICC can be anatomically divided into two subtypes: the large duct type (mucin-production ICC, muc-ICC) and the small duct type (mixed-ICC) origins from hepatic progenitor cells (HPCs). The immunoreactivity of S100P and neural cell adhesion molecule (NCAM) are useful biomarkers to distinguish the two subtypes. In this study, we report a difficult-to-diagnose case of metastatic retroperitoneal tumor of occult hepatolithiasis-associated ICC. Besides, this case was both positive for S100P and NCAM, considered as a rare muc-ICC with the HPCs features. Tumor whole exome sequencing detection results by Genetron (China) revealed that there were 41 gene mutations in this patient. The SMAD4-p.His530ThrfsTer47 and KRAS-p.Gly12Val mutation might promote the occurrence and distant metastasis of the tumor.

Objective:To detect the expression of GINS complex subunit 4 (GINS4) protein in hepatocellular carcinoma tissues and observe its effect on the invasion and proliferation of hepatocellular carcinoma cells.Methods:From September 2019 to December 2020 in our hospital, 60 patients with hepatocellular carcinoma were collected during surgery and hepatocellular carcinoma tissues and corresponding para-cancerous tissue specimens were selected as the observation group and the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting was used to detect the expression of GINS4 in hepatocellular carcinoma tissues, use specific short hairpin RNA (shRNA) to construct low-expressing stable hepatocellular carcinoma cell lines, and divide them into experimental groups (shRNA group) and the control group (NC group); Transwell tested its ability to invade HepG2 cells; colony formation test and cell counting kit (CCK-8) test tested its proliferation ability on HepG2 cells. Comparison between groups is by paired sample t test. Results:RT-qPCR showed that the expression of GINS4 in hepatocellular carcinoma tissues (2.89±0.11) was higher than that in adjacent tissues (1.34±0.15), and the difference was statistically significant ( t=8.56, P<0.01). Western blot showed that the expression of GINS4 in hepatocellular carcinoma tissue was (1.54±0.76) times higher than that in adjacent tissues, and the difference was statistically significant ( t=2.67, P<0.05). After shRNA transfection of HepG2 cells, GINS4 in the experimental group The expression level was (1.88±0.34) times lower than that of the control group, and the difference was statistically significant ( t=7.43, P<0.05); the Transwell experiment showed that the number of perforated cells in the experimental group was (56.33±3.51) compared with the control group (90.42±1.53) cells were significantly reduced, and the difference was statistically significant ( t=3.34, P<0.01); the colony formation experiment showed that the number of cell clusters in the experimental group (83.33±7.37) was significantly less than that in the control group (345.00±16.64). The difference was statistically significant ( t=15.28, P<0.01); CCK-8 experiment showed that the 3 d absorbance of the experimental group was (1.43±0.11) lower than that of the control group (2.15±0.15), and the difference was statistically significant ( t=6.52, P<0.001). Conclusion:The expression of GINS4 in hepatocellular carcinoma tissues is higher than that in adjacent tissues. Reducing the expression of GINS4 can significantly inhibit the invasion and proliferation of hepatocellular carcinoma cells.

Objective:To investigate the application of nano-fluorescent probes in hepatocellular carcinoma (HCC) blood supply molecular imaging in rats and pave the foundation of double blood supply treatment in HCC.Methods:The HCC models of 12 rats were established by diethylnitrosamine (DEN) chemical induction. After 15 weeks, the magnetic resonance imaging (MRI) and pathological findings were observed. Different nano-fluorescent probes were applied through hepatic artery and portal vein to observe the blood supply molecular images of HCC tissues.Results:A total of 4 rats died at 13-14 weeks, with a survival rate of 66.67% at 15 weeks and the tumor formation rate of 100%. The pathological sections were consistent with the signs of HCC. The arterial 1, 1′-dioctadecy1-3, 3, 3′, 3′-tetramethylindocarbocyanine perchlorate (DiI) fluorescence intensity in tumor of molecular fluorescence imaging [(2.99±0.41)×10 7] was significantly greater than the surrounding liver tissue [(1.06±0.22)×10 7, t=-9.410, P<0.05]; and fluorescence intensity of Alexa fluor 647 in tumor of portal vein [(1.30±0.29)×10 7] was significantly weaker than that of peripheral liver tissue [(2.76±0.38)×10 7, t=7.480, P<0.05]. The slide scan showed that arterial blood supply in tumor tissue was higher than the surrounding liver tissue, and the portal vein blood supply was found in the parenchyma and surrounding areas of the liver tumor. Conclusion:The DEN induction is a mature and stable method to establish the HCC model, and the nano-fluorescent probe can observe the double blood supply for HCC in the microscopic level.