Gui-qiu Liu

Bio: Gui-qiu Liu is an academic researcher from Tianjin Medical University. The author has contributed to research in topics: Cancer & Radiology. The author has an hindex of 3, co-authored 5 publications receiving 20 citations.

Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes.

Abstract: Adhesion molecules distributed on the cell-surface depends upon their dynamic trafficking that plays an important role during cancer progression. ADP-ribosylation factor 6 (Arf6) is a master regulator of membrane trafficking. CD147, a tumor-related adhesive protein, can promote the invasion of liver cancer. However, the role of Arf6 in CD147 trafficking and its contribution to liver cancer progression remain unclear. Stable liver cancer cell lines with Arf6 silencing and over-expression were established. Confocal imaging, flow cytometry, biotinylation and endomembrane isolation were used to detect CD147 uptake and recycling. GST-pull down, gelatin zymography, immunofluorescence, cell adhesion, aggregation and tight junction formation, Transwell migration, and invasion assays were used to examine the cellular phenotypes. GEPIA bioinformatics, patient’s specimens and electronic records collection, and immunohistochemistry were performed to obtain the clinical relevance for Arf6-CD147 signaling. We found that the endocytic recycling of CD147 in liver cancer cells was controlled by Arf6 through concurrent Rab5 and Rab22 activation. Disruption of Arf6-mediated CD147 trafficking reduced the cell-matrix and cell-cell adhesion, weakened cell aggregation and junction stability, attenuated MMPs secretion and cytoskeleton reorganization, impaired HGF-stimulated Rac1 activation, and markedly decreased the migration and invasion of liver cancer cells. Moreover, high-expression of the Arf6-CD147 signaling components in HCC (hepatocellular carcinoma) was closely correlated with poor clinical outcome of patients. Our results revealed that Arf6-mediated CD147 endocytic recycling is required for the malignant phenotypes of liver cancer. The Arf6-driven signaling machinery provides excellent biomarkers or therapeutic targets for the prevention of liver cancer.

Endometrial stromal sarcoma with endometrioid adenocarcinoma of the uterus: a case report.

Abstract: Endometrial stromal sarcoma (ESS) is a rare malignant neoplasm of the uterus. We report the first case of undifferentiated ESS (UES) coexistent with grade 1 endometrioid adenocarcinoma in a 73-year-old female who presented with irregular vaginal bleeding for 4 days after menopause 20 years. Imaging examination including Magnetic Resonance Imaging (MRI) demonstrated multi-node reflection in uterine cavity without metastatic lesions, and the endometrium essentially normal. Grossly, a grey-red breakable polypoid tumor of 4.5 × 3.0 ×2.0 cm was recognized in the posterior uterine wall with surrounding slight rough endometrium. Microscopically, the tumor was composed of a larger component of undifferentiated stromal sarcoma that was distinct from a smaller endometrioid adenocarcinoma. The separate components of the tumor could be supported in immunohistochemical studies. There was no sign of recurrence for postoperative 6 months.

Perinodular ductular reaction/epithelial cell adhesion molecule loss in small hepatic nodules

Abstract: AIM: To investigate if loss of epithelial cell adhesion molecule (EpCAM) is associated with microinvasion in hepatocellular carcinomas (HCCs) in the presence of chronic hepatitis B. METHODS: The expression of EpCAM, cytokeratin 7 (CK7) and CK19 in 112 hepatic nodules was studied, including 20 HCCs with nodules ≤ 3 cm, 26 HCCs with nodules > 3 cm, 20 high-grade dysplastic nodules, 26 cirrhotic, large regenerative nodules and 20 cases of cirrhosis. RESULTS: Membranes of ductular reaction (DR) hepatobiliary cells, interlobular bile duct and some hepatic cells were positive for EpCAM expression. Active expression of DR/EpCAM was observed in the majority of noninvasive nodules (50/66, 75.76%); however, expression was absent in the major area of invasion in HCCs (42/46, 91.30%). DR/EpCAM loss in HCCs ≤ 3 cm was higher than in high-grade dysplastic nodules (HGDNs) (P 3 cm, 20 HGDNs) with DR/EpCAM expression had a higher overall survival rate (P 0.05). The diagnostic specificity and diagnostic accuracy were both increased when DR/EpCAM, DR/CK7 and DR/CK19 were combined (P < 0.01). CONCLUSION: DR/EpCAM loss may be a useful marker for determining microinvasion in HCCs ≤ 3 cm, but also for predicting prognosis.

[Diagnostic value of absent ductular reaction at hepatocellular-stromal boundaries in early stage hepatocellular carcinoma].

Abstract: Objective To investigate the role of absent ductular reaction (DR) at hepatocellular-stromal boundaries in early stage hepatocellular carcinoma (HCC) with cirrhosis in patients with chronic hepatitis B. Methods Cytokeratin (CK)7 and CK19 expression was detected by the SP immunohistochemistry method in 112 hepatic nodules taken from 20 cases of early HCC, 26 cases of HCC with nodules more than 3 cm, 20 cases of high-grade dysplastic nodule (HGDN), 26 cases of low-grade dysplastic nodule (LGDN), and 20 cases of cirrhosis (CIR). DR/CK7 and DR/CK19 were assessed separately on a semi-quantitative scale and statistically analyzed. Results The mean age of the patients in the study was 53.71 years-old, and the study population consisted of 73 males and 39 females. The follow-up time ranged from 3 to 90 months. Positive CK7 and CK19 staining was detected in the cytoplasm of DR-positive hepatobiliary cells, interlobular bile duct, and a portion of hepatic cells. All of the DR/CK7- and DR/CK19-positive cells were localized around the non-invasive nodules. Specimens with focal or diffuse DR/CK7- and DR/CK19-loss had more robust stromal invasion. Specimens from early HCC cases showed greater DR/CK19 loss than specimens from HGDN cases, LGDN cases and CIR cases (all P less than 0.01). DR/CK7 loss of early HCC was less than HCC with nodules more than 3 cm (P less than 0.05), and more than LGDN cases and CIR cases (both P less than 0.01).The area under the receiver operating characteristic curve of DR/CK7 was very similar to that of DR/CK19 (P more than 0.05). Pearson's correlation analysis indicated that DR/CK7 and DR/CK19 were positively correlated with tumor-free time (P less than 0.01) and negatively correlated with early recurrence time as well as death rate (both P less than 0.01). Furthermore, cases showing DR/CK7 or DR/CK19 loss had lower overall survival rate and tumor-free survival rate (P less than 0.01) and higher early recurrence rate (P less than 0.01). Conclusion DR/CK7 and DR/CK19 immunostaining may help to distinguish non-invasive HGDNs from both minimally-invasive and overtly-invasive HCCs by identifying small foci of invasion and predicting increased risk of invasiveness.

Typical carcinoid tumor of the larynx with inguinal lymphatic metastasis

Abstract: 患者 男，55岁，因咽异物感半年入院。入院前半年，患者无明显诱因出现咽部异物感，同时伴有睡眠时打鼾；但患者无咽痛、咳嗽、声音嘶哑、呼吸困难、饮水呛咳以及吞咽困难等症状。近1个月患者自觉讲话含糊不清，低头伴有轻度呼吸困难，以及唾液中带有血丝。

The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective.

Abstract: The Adenosine diphosphate-Ribosylation Factor (ARF) family belongs to the RAS superfamily of small GTPases and is involved in a wide variety of physiological processes, such as cell proliferation, motility and differentiation by regulating membrane traffic and associating with the cytoskeleton. Like other members of the RAS superfamily, ARF family proteins are activated by Guanine nucleotide Exchange Factors (GEFs) and inactivated by GTPase-Activating Proteins (GAPs). When active, they bind effectors, which mediate downstream functions. Several studies have reported that cancer cells are able to subvert membrane traffic regulators to enhance migration and invasion. Indeed, members of the ARF family, including ARF-Like (ARL) proteins have been implicated in tumorigenesis and progression of several types of cancer. Here, we review the role of ARF family members, their GEFs/GAPs and effectors in tumorigenesis and cancer progression, highlighting the ones that can have a pro-oncogenic behavior or function as tumor suppressors. Moreover, we propose possible mechanisms and approaches to target these proteins, toward the development of novel therapeutic strategies to impair tumor progression.

Identification of Ferroptosis Genes In Immune Infiltration and Prognosis In Thyroid Papillary Carcinoma Using Network Analysis

Abstract: Background Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. While many patients survive, a portion of PTC cases display high aggressiveness and even develop into refractory differentiated thyroid carcinoma. This may be alleviated by developing a novel model to predict the risk of recurrence. Ferroptosis is an iron-dependent form of regulated cell death (RCD) driven by lethal accumulation of lipid peroxides, is regulated by a set of genes and shows a variety of metabolic changes. To elucidate whether ferroptosis occurs in PTC, we analyse the gene expression profiles of the disease and established a new model for the correlation. Methods The thyroid carcinoma (THCA) datasets were downloaded from The Cancer Genome Atlas (TCGA), UCSC Xena and MisgDB, and included 502 tumour samples and 56 normal samples. A total of 60 ferroptosis related genes were summarised from MisgDB database. Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) were used to analyse pathways potentially involving PTC subtypes. Single sample GSEA (ssGSEA) algorithm was used to analyse the proportion of 28 types of immune cells in the tumour immune infiltration microenvironment in THCA and the hclust algorithm was used to conduct immune typing according to the proportion of immune cells. Spearman correlation analysis was performed on the ferroptosis gene expression and the correlation between immune infiltrating cells proportion. We established the WGCNA to identify genes modules that are highly correlated with the microenvironment of immune invasion. DEseq2 algorithm was further used for differential analysis of sequencing data to analyse the functions and pathways potentially involving hub genes. GO and KEGG enrichment analysis was performed using Clusterprofiler to explore the clinical efficacy of hub genes. Univariate Cox analysis was performed for hub genes combined with clinical prognostic data, and the results was included for lasso regression and constructed the risk regression model. ROC curve and survival curve were used for evaluating the model. Univariate Cox analysis and multivariate Cox analysis were performed in combination with the clinical data of THCA and the risk score value, the clinical efficacy of the model was further evaluated. Results We identify two subtypes in PTC based on the expression of ferroptosis related genes, with the proportion of cluster 1 significantly higher than cluster 2 in ferroptosis signature genes that are positively associated. The mutations of Braf and Nras are detected as the major mutations of cluster 1 and 2, respectively. Subsequent analyses of TME immune cells infiltration indicated cluster 1 is remarkably richer than cluster 2. The risk score of THCA is in good performance evaluated by ROC curve and survival curve, in conjunction with univariate Cox analysis and multivariate Cox analysis results based on the clinical data shows that the risk score of the proposed model could be used as an independent prognostic indicator to predict the prognosis of patients with papillary thyroid cancer. Conclusions Our study finds seven crucial genes, including Ac008063.2, Apoe, Bcl3, Acap3, Alox5ap, Atxn2l and B2m, and regulation of apoptosis by parathyroid hormone-related proteins significantly associated with ferroptosis and immune cells in PTC, and we construct the risk score model which can be used as an independent prognostic index to predict the prognosis of patients with PTC.

SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner

Abstract: ABSTRACT The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically.

Utility of diffusion-weighted and contrast-enhanced magnetic resonance imaging in diagnosing and differentiating between high- and low-grade uterine endometrial stromal sarcoma.

Abstract: Endometrial stromal sarcoma (ESS) is a rare uterine malignancy that features different prognoses for its high- and low-grade subtypes. We investigated the diagnostic accuracy of magnetic resonance (MR) imaging in diagnosing and differentiating between high- and low-grade ESS. We retrospectively reviewed the preoperative pelvic MR images of consecutive patients who received histologically confirmed diagnoses of high-grade ESS (n = 11) and low-grade ESS (n = 9) and T2-hyperintense leiomyoma (n = 16). Two radiologists independently evaluated imaging features in T1-, T2-, and diffusion-weighted and contrast-enhanced MR images. Statistical analysis included Mann-Whitney tests and Fisher’s exact test, with sensitivity, specificity and diagnostic accuracy of imaging features. High-grade ESS was associated with significantly more extensive necrosis and hemorrhage and distinct feather-like enhancement compared with low-grade ESS (P < .05 for all). The feather-like enhancement pattern yielded a diagnostic accuracy of 95%, sensitivity of 91%, and specificity of 100% in differentiating high-grade from low-grade ESS. This imaging characteristic was significantly superior to the necrosis (80%, P = .033) or hemorrhage (75%, P = .007). Both high- and low-grade ESS demonstrated T2 hypointense bands, marginal nodules, intratumoral nodules, and worm-like intra-myometrial nodules, and their tumor apparent diffusion coefficient (ADC) values were significantly lower than those of T2-hyperintense leiomyomas (P < .001). Diffusion-weighted MR imaging is useful in diagnosing ESS against T2-hyperintense leiomyomas, and contrast enhancement aids in further differentiating between high- and low-grade ESS.