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Article ; Online: Integrated clinical and prognostic analyses of mTOR/Hippo pathway core genes in hepatocellular carcinoma.

Feng, Tianhang / Chen, Ping / Wang, Tao / Lai, Chunyou / Yao, Yutong

2024 Volume 80, Issue 2, Page(s) 439–449

Abstract: Hepatocellular carcinoma (HCC) is one of the most aggressive and dismal cancers globally. Emerging evidence has established that mTOR and Hippo pathways are oncogenic drivers of HCC. However, the prognostic value of these pathways in HCC remains unclear. ...

Abstract	Hepatocellular carcinoma (HCC) is one of the most aggressive and dismal cancers globally. Emerging evidence has established that mTOR and Hippo pathways are oncogenic drivers of HCC. However, the prognostic value of these pathways in HCC remains unclear. In this study, we aimed to develop a gene signature utilizing the mTOR/Hippo genes for HCC prognostication. A multiple stage strategy was employed to screen, and a 12-gene signature based on mTOR/Hippo pathways was constructed to predict the prognosis of HCC patients. The risk scores calculated by the signature were inversely correlated with patient prognosis. Validation of the signature in independent cohort confirmed its predictive power. Further analysis revealed molecular differences between high and low-risk groups at genomic, transcriptomic, and protein-interactive levels. Moreover, immune infiltration analysis revealed an immunosuppressive state in the high-risk group. Finally, the gene signature could predict the sensitivity to current chemotherapeutic drugs. This study demonstrated that combinatorial mTOR/Hippo gene signature was a robust and independent prognostic tool for survival prediction of HCC. Our findings not only provide novel insights for the molecular understandings of mTOR/Hippo pathways in HCC, but also have important clinical implications for guiding therapeutic strategies.
MeSH term(s)	Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/mortality ; Liver Neoplasms/metabolism ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/mortality ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; TOR Serine-Threonine Kinases/metabolism ; TOR Serine-Threonine Kinases/genetics ; Prognosis ; Gene Expression Regulation, Neoplastic ; Female ; Hippo Signaling Pathway ; Male ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Signal Transduction ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Middle Aged ; Gene Expression Profiling ; Transcriptome
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.11.1) ; MTOR protein, human (EC 2.7.1.1) ; Biomarkers, Tumor ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2024-03-12
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1325104-1
ISSN	1877-8755 ; 0034-9402 ; 1138-7548
ISSN (online)	1877-8755
ISSN	0034-9402 ; 1138-7548
DOI	10.1007/s13105-024-01015-0
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Article ; Online: Correction: Impact of preoperative antiviral therapy on the prognosis of hepatitis B virus-related hepatocellular carcinoma.

Liang, Yuxin / Zhong, Deyuan / Zhang, Zilong / Su, Yuhao / Yan, Su / Lai, Chunyou / Yao, Yutong / Shi, Ying / Huang, Xiaolun / Shang, Jin

BMC cancer

2024 Volume 24, Issue 1, Page(s) 343

Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Published Erratum
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-024-12108-w
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Article ; Online: Impact of preoperative antiviral therapy on the prognosis of hepatitis B virus-related hepatocellular carcinoma.

Liang, Yuxin / Zhong, Deyuan / Zhang, Zilong / Su, Yuhao / Yan, Su / Lai, Chunyou / Yao, Yutong / Shi, Ying / Huang, Xiaolun / Shang, Jin

BMC cancer

2024 Volume 24, Issue 1, Page(s) 291

Abstract: Background: For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral ... ...

Abstract	Background: For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. Methods: 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People's Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. Results: NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA < 1000 copy/mL had significantly better recurrence-free survival (RFS) and OS than those with HBV DNA ≥ 1000 copy/mL (HR: 7.783; P = 0.002; HR: 6.699; P < 0.001). However, the differences of RFS and OS rates between entecavir group and tenofovir disoproxil fumarate group were not statistically significant. Similar results were also observed in the rates of early VR, BR and combined VR and BR. Conclusion: Timely and reasonable preoperative NAs therapy showed clinical benefit in improving the prognosis of patients with HBV-related HCC, even in the case of normal alanine aminotransferase (ALT) level and negative hepatitis e antigen (HBeAg). Furthermore, a possible synergistic effect between antiviral therapy and anti-PD-1 therapy was founded and need further verification.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/surgery ; Hepatitis B virus ; DNA, Viral ; Hepatitis B, Chronic/complications ; Hepatitis B, Chronic/drug therapy ; Liver Neoplasms/drug therapy ; Liver Neoplasms/surgery ; Prognosis ; Antiviral Agents/therapeutic use
Chemical Substances	DNA, Viral ; Antiviral Agents
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-024-12031-0
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Article: Development of ensemble learning models for prognosis of hepatocellular carcinoma patients underwent postoperative adjuvant transarterial chemoembolization.

Liang, Yuxin / Wang, Zirui / Peng, Yujiao / Dai, Zonglin / Lai, Chunyou / Qiu, Yuqin / Yao, Yutong / Shi, Ying / Shang, Jin / Huang, Xiaolun

Frontiers in oncology

2023 Volume 13, Page(s) 1169102

Abstract: Background: Postoperative adjuvant transarterial chemoembolization (PA-TACE) has been increasing widely used to improve the prognosis of hepatocellular carcinoma (HCC) patients. However, clinical outcomes vary from patient to patient, which calls for ... ...

Abstract	Background: Postoperative adjuvant transarterial chemoembolization (PA-TACE) has been increasing widely used to improve the prognosis of hepatocellular carcinoma (HCC) patients. However, clinical outcomes vary from patient to patient, which calls for individualized prognostic prediction and early management. Methods: A total of 274 HCC patients who underwent PA-TACE were enrolled in this study. The prediction performance of five machine learning models was compared and the prognostic variables of postoperative outcomes were identified. Results: Compared with other machine learning models, the risk prediction model based on ensemble learning strategies, including Boosting, Bagging, and Stacking algorithms, presented better prediction performance for overall mortality and HCC recurrence. Moreover, the results showed that the Stacking algorithm had relatively low time consumption, good discriminative ability, and the best prediction performance. In addition, according to time-dependent ROC analysis, the ensemble learning strategies were found to perform well in predicting both OS and RFS for the patients. Our study also found that BCLC Stage, hsCRP/ALB and frequency of PA-TACE were relatively important variables in both overall mortality and recurrence, while MVI contributed more to the recurrence of the patients. Conclusion: Among the five machine learning models, the ensemble learning strategies, especially the Stacking algorithm, could better predict the prognosis of HCC patients following PA-TACE. Machine learning models could also help clinicians identify the important prognostic factors that are clinically useful in individualized patient monitoring and management.
Language	English
Publishing date	2023-05-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1169102
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Article ; Online: ST8SIA6-AS1 contributes to hepatocellular carcinoma progression by targeting miR-142-3p/HMGA1 axis.

Feng, Tianhang / Yao, Yutong / Luo, Le / Zou, Haibo / Xiang, Guangming / Wei, Lingling / Yang, Qinyan / Shi, Ying / Huang, Xiaolun / Lai, Chunyou

Scientific reports

2023 Volume 13, Issue 1, Page(s) 650

Abstract: Hepatocellular carcinoma (LIHC) accounts for 90% of all liver cancers and is a serious health concern worldwide. Long noncoding RNAs (lncRNAs) have been observed to sponge microRNAs (miRNAs) and participate in the biological processes of LIHC. This study ...

Abstract	Hepatocellular carcinoma (LIHC) accounts for 90% of all liver cancers and is a serious health concern worldwide. Long noncoding RNAs (lncRNAs) have been observed to sponge microRNAs (miRNAs) and participate in the biological processes of LIHC. This study aimed to evaluate the role of the ST8SIA6-AS1-miR-142-3p-HMGA1 axis in regulating LIHC progression. RT-qPCR and western blotting were performed to determine the levels of ST8SIA6-AS1, miR-142-3p, and HMGA1 in LIHC. The relationship between ST8SIA6-AS1, miR-142-3p, and HMGA1 was assessed using luciferase assay. The role of the ST8SIA6-AS1-miR-142-3p-HMGA1 axis was evaluated in vitro using LIHC cells. Expression of ST8SIA6-AS1 and HMGA1 was significantly upregulated, whereas that of miR-142-3p was markedly lowered in LIHC specimens and cells. ST8SIA6-AS1 accelerated cell growth, invasion, and migration and suppressed apoptosis in LIHC. Notably, ST8SIA6-AS1 inhibited HMGA1 expression by sponging miR-142-3p in LIHC cells. In conclusion, sponging of miR-142-3p by ST8SIA6-AS1 accelerated the growth of cells while preventing cell apoptosis in LIHC cells, and the inhibitory effect of miR-142-3p was abrogated by elevating HMGA1 expression. The ST8SIA6-AS1-miR-142-3p-HMGA1 axis represents a potential target for the treatment of patients with LIHC.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; HMGA1a Protein/genetics ; HMGA1a Protein/metabolism ; Cell Line, Tumor ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Transcription Factors/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Cell Movement/genetics ; Sialyltransferases/metabolism
Chemical Substances	HMGA1a Protein (124544-67-8) ; MicroRNAs ; Transcription Factors ; RNA, Long Noncoding ; ST8SIA6 protein, human (EC 3.4.99.-) ; Sialyltransferases (EC 2.4.99.-) ; MIRN142 microRNA, human
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-26643-8
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Article ; Online: Single-cell profiling reveals the heterogeneity of NK cells during anti-PD-1 therapy in non-small-cell lung cancer.

Shang, Jin / Li, Lin / Lai, Chunyou / Feng, Tianhang / Yao, Yutong / Zhong, Deyuan / Liang, Yuxin / Huang, Xiaolun / Yang, Qinyan / Shi, Ying

International immunopharmacology

2023 Volume 124, Issue Pt A, Page(s) 110743

Abstract: Background: The efficacy of immune checkpoint inhibitors remains limited in non-small cell lung cancer (NSCLC). Natural killer (NK) cells serve as the key element of innate immunity and play an important role in anti-tumor immunity, the impact of NK ... ...

Abstract	Background: The efficacy of immune checkpoint inhibitors remains limited in non-small cell lung cancer (NSCLC). Natural killer (NK) cells serve as the key element of innate immunity and play an important role in anti-tumor immunity, the impact of NK cells on efficacy of anti-PD-1 therapy in NSCLC is worth exploring. Methods: We analyzed single-cell transcriptome data derived from biopsies of NSCLC patients receiving anti-PD-1 treatment. Immune cell subtypes were identified and further cell-cell communication were analyzed and verified. Results: We observed totally 6 distinct NK cells clusters in NSCLC infiltrating immune cells. It's worth noting that enrichment of immature NK cells was found in responsive group. A series of marker genes of immature NK cells were associated with anti-PD-1 response and related to immune regulation processes such as antigen processing, Th1, Th17 cells activation. Moreover, effector CD8 Conclusions: In conclusion, immature NK cells may facilitate the efficacy of anti-PD-1 therapy by interacting with Th1 cells, Th17 cells and enhancing infiltration of effector CD8
Language	English
Publishing date	2023-08-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.110743
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Article: Umbilical cord blood-derived mesenchymal stem cells transplantation decreases incidence of liver cancer in end-stage liver disease patients: a retrospective analysis over 5 years.

Luo, Le / Lai, Chunyou / Feng, Tianhang / Yao, Yutong / Xue, Hua / Xiang, Guangming / Luo, Lanyun / Huang, Xiaolun

American journal of translational research

2022 Volume 14, Issue 8, Page(s) 5848–5858

Abstract: Objective: To investigate effects of umbilical cord blood-derived mesenchymal stem cells (UC-MSCs) transplantation on the risks of liver cancers in end-stage liver disease (ESLD) patients.: Methods: Data of 45 ESLD patients received UC-MSCs ... ...

Abstract	Objective: To investigate effects of umbilical cord blood-derived mesenchymal stem cells (UC-MSCs) transplantation on the risks of liver cancers in end-stage liver disease (ESLD) patients. Methods: Data of 45 ESLD patients received UC-MSCs transplantation (UC-MSCs group) and 50 ESLD patients received non-UC-MSCs transplantation (non-UC-MSCs group) were retrospectively analyzed, and they were followed up for 5 years. Results: The incidence of liver cancer was much lower in UC-MSCs group than that in the non-UC-MSCs group (12% vs 2.2%, P=0.008). The survival rate of patients was significantly higher in the UC-MSCs group than that in the non-UC-MSCs group during the five years follow-up (P=0.043). The inflammation and fibrosis scores were lower in the UC-MSCs group than those in the non-UC-MSCs group (P<0.036). Compared with the non-UC-MSCs group, the UC-MSCs group showed largely improved liver cirrhosis degree and lower Child-Pugh scores (P<0.05). Conclusions: UC-MSCs transplantation is able to decrease the risks of liver cancers in ESLD patients, which might work by inhibiting inflammation.
Language	English
Publishing date	2022-08-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2471058-1
ISSN	1943-8141
ISSN	1943-8141
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Article ; Online: Comparative study of indocyanine green (ICG)-R15 and Albumin-Indocyanine Green Evaluation (ALICE) grading system in the prediction of posthepatectomy liver failure and postoperative mortality in patients with hepatic alveolar echinococcosis.

Liang, Yuxin / Zhang, Zilong / Dai, Zonglin / Cao, Rui / Zhong, Deyuan / Lai, Chunyou / Yao, Yutong / Feng, Tianhang / Huang, Xiaolun

BMC gastroenterology

2022 Volume 22, Issue 1, Page(s) 297

Abstract: Background: A precise evaluation of liver reserve function in patients with hepatic alveolar echinococcosis (HAE) prior to hepatectomy could substantially increase the success rate of the operation and reduce the incidence of postoperative complications. ...

Abstract	Background: A precise evaluation of liver reserve function in patients with hepatic alveolar echinococcosis (HAE) prior to hepatectomy could substantially increase the success rate of the operation and reduce the incidence of postoperative complications. The present study aimed to investigate the significance of the indocyanine green retention test at 15 min (ICG-R15) and the Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting severe posthepatectomy liver failure (PHLF) and postoperative mortality in HAE patients undergoing liver resection. Methods: A total of 105 HAE patients undergoing hepatectomy were enrolled in this study. The value of each variable in predicting severe PHLF was evaluated by univariate and multivariate logistic regression analyses. The area under the receiver operating characteristic (ROC) curves (AUC) were calculated to evaluate the predictive ability of the Child-Pugh grade, ICG-R15, and ALICE grading system. Also, patients were classified using the optimal cutoff value for ICG-R15 and different ALICE grades, and the incidence of severe PHLF and postoperative mortality were compared with the predicted values. Results: Out of the 105 HAE patients enrolled in this study, 34 patients (32.4%) developed severe PHLF. The ALICE grade and operative time were identified as independent predictors of severe PHLF. According to ROC analysis, the AUCs of the Child-Pugh grade, ICG-R15, and ALICE grade for predicting severe PHLF were 0.733 (95% confidence interval (CI), 0.637-0.814), 0.823 (95% CI, 0.737-0.891), 0.834 (95% CI, 0.749-0.900). The incidence of severe PHLF and postoperative 90-day mortality in patients with ICG-R15 > 7.2% were significantly higher than those with ICG-R15 ≤ 7.2% (P < 0.001; P = 0.008). Likewise, the incidence of severe PHLF and postoperative 90-day mortality in patients with ALICE grade 2 were higher than those with ALICE grade 1 within the Child-Pugh grade A (P < 0.001; P = 0.083). Conclusion: ICG-R15 and ALICE grading system are powerful predictors of severe PHLF and postoperative mortality among HAE patients undergoing hepatectomy. Furthermore, a combination of the preoperative Child-Pugh grade and ALICE grading system may provide an even more precise and objective guidance and facilitate surgical decision-making for HAE patients.
MeSH term(s)	Albumins ; Carcinoma, Hepatocellular/complications ; Echinococcosis, Hepatic/surgery ; Hepatectomy/adverse effects ; Humans ; Indocyanine Green ; Liver Failure/etiology ; Liver Failure/surgery ; Liver Function Tests ; Liver Neoplasms/surgery ; Retrospective Studies
Chemical Substances	Albumins ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2022-06-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2041351-8
ISSN	1471-230X ; 1471-230X
ISSN (online)	1471-230X
ISSN	1471-230X
DOI	10.1186/s12876-022-02367-x
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Article: The prognostic significance of inflammation-immunity-nutrition score on postoperative survival and recurrence in hepatocellular carcinoma patients.

Liang, Yuxin / Zhang, Zilong / Zhong, Deyuan / Lai, Chunyou / Dai, Zonglin / Zou, Haibo / Feng, Tianhang / Shang, Jin / Shi, Ying / Huang, Xiaolun

Frontiers in oncology

2022 Volume 12, Page(s) 913731

Abstract: Background: Inflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and ... ...

Abstract	Background: Inflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery. Methods: A total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson's χ2 test or Fisher's exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model. Results: The patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P<0.001; P=0.004). In terms of clinical prognosis, IINS-AFP classification was good in group I, moderate in group II, and poor in group III. Group I had a longer OS (P<0.001) and PFS (P=0.008) compared with group II and III. ROC analysis revealed that IINS-AFP classification had a better prognostic performance for OS (AUC: 0.767) and PFS (AUC: 0.641) than other predictors, excluding its slightly lower predictive power for PFS than IINS. The time-dependent ROC curves also showed that both IINS (12-month AUC: 0.650; 24-month AUC: 0.670; 36-month AUC: 0.880) and IINS-AFP classification (12-month AUC: 0.720; 24-month AUC: 0.760; 36-month AUC: 0.970) performed well in predicting OS for HCC patients. Furthermore, the internal validation and external validation proved that IINS had good predictive performance, strong internal validity and external applicability, and could be used to establish the prediction model. Conclusion: Inflammation-immunity-nutrition score could be a powerful clinical prognostic indicator in HCC patients undergoing radical surgery. Furthermore, IINS-AFP classification presents better prognostic performance than IINS or AFP alone, and might serve as a practical guidance to help patients adjust treatment and follow-up strategies to improve future outcomes.
Language	English
Publishing date	2022-08-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.913731
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Article ; Online: ITGA5 and ITGB1 contribute to Sorafenib resistance by promoting vasculogenic mimicry formation in hepatocellular carcinoma.

Shi, Ying / Shang, Jin / Li, Yan / Zhong, Deyuan / Zhang, Zilong / Yang, Qinyan / Lai, Chunyou / Feng, Tianhang / Yao, Yutong / Huang, Xiaolun

Cancer medicine

2022 Volume 12, Issue 3, Page(s) 3786–3796

Abstract: Background: Hepatocellular carcinoma (HCC) is labeled with high mortality and tolerance to chemotherapy. Sorafenib has been the first-line treatment option in HCC patients for past decades, while the therapeutic effect was limited in almost HCC patients. ...

Abstract	Background: Hepatocellular carcinoma (HCC) is labeled with high mortality and tolerance to chemotherapy. Sorafenib has been the first-line treatment option in HCC patients for past decades, while the therapeutic effect was limited in almost HCC patients. Methods: In this study, we analyzed public omics data of HCC patients with different responses to Sorafenib treatment. To confirm the role of integrins A5 and B1 (ITGA5 and ITGB1) in Sorafenib resistance, we generated the Sorafenib-resistant (Sor-R) cell lines and cells overexpressing ITGA5 or ITGB1. Hypoxia level was measured using Hypoxy probe by flow cytometry, while vasculogenic mimicry was detected and quantified by CD31 and periodic acid schiff staining. Results: Hypoxia was upregulated in non-responsive patients, accompanied with genes involved in encoding extracellular matrix components and angiogenesis such as ITGA5 and ITGB1. Sor-R hepatoma cell lines were constructed to measure expression and role of candidate genes. ITGA5 and ITGB1 were augmented in Sor-R cells. Upregulation of ITGA5 or ITGB1 reduced the sensitivity to Sorafenib in HepG2 and Huh7 cells, aggravated the hypoxic condition and resulted in formation of vascular mimicry. Conclusions: These findings suggested that hypoxia associated vascular mimicry account for non-response to Sorafenib treatment in HCC patients. ITGA5 and ITGB1 may serve as effective predictors of HCC patients' outcome after Sorafenib treatment, which also provides a new target for HCC patients resistant to Sorafenib.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/pathology ; Sorafenib/therapeutic use ; Liver Neoplasms/pathology ; Drug Resistance, Neoplasm/genetics ; Cell Line, Tumor ; Hypoxia
Chemical Substances	Sorafenib (9ZOQ3TZI87)
Language	English
Publishing date	2022-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.5110
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