Cancer Immunotherapy and Medical Imaging Research Trends from 2003 to 2023: A Bibliometric Analysis.

Purpose: With the rapid development of immunotherapy, cancer treatment has entered a new phase. Medical imaging, as a primary diagnostic method, is closely related to cancer immunotherapy. However, until now, there has been no systematic bibliometric analysis of the state of this field. Therefore, the main purpose of this article is to clarify the past research trajectory, summarize current research hotspots, reveal dynamic scientific developments, and explore future research directions. Patients and Methods: A comprehensive search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to immunotherapy specifically for the medical imaging of carcinoma. The search spanned the period from the year 2003 to 2023. Several analytical tools were employed. These included CiteSpace (6.2.4), and the Microsoft Office Excel (2016). Results: By searching the database, a total of 704 English articles published between 2003 and 2023 were obtained. We have observed a rapid increase in the number of publications since 2018. The two most active countries are the United States (n=265) and China (n=170). Pittock, Sean J and Abu-sbeih, Hamzah are very concerned about the relationship between cancer immunotherapy and medical images and have published more academic papers (n = 5; n = 4). Among the top 10 co-cited authors, Topalian Sl (n=43) cited ranked first, followed by Graus F (n=40) cited. According to clustering, timeline, and burst word analysis, the results show that the current research focus is on "MRI", "deep learning", "tumor microenvironment" and so on. Conclusion: Medical imaging and cancer immunotherapy are hot topics. The United States is the country with the most publications and the greatest influence in this field, followed by China. "MRI", "PET/PET-CT", "deep learning", "immune-related adverse events" and "tumor microenvironment" are currently hot research topics and potential targets.

Lipid Isobaric Mass Tagging for Enhanced Relative Quantification of Unsaturated sn-Positional Isomers.

Changes in the levels of lipid sn-positional isomers are associated with perturbation of the physiological environment within the biological system. Consequently, knowing the concentrations of these lipids holds significant importance for unraveling their involvement in disease diagnosis and pathological mechanisms. However, existing methods for lipid quantification often fall short in accuracy due to the structural diversity and isomeric forms of lipids. To address this challenge, we have developed an aziridine-based isobaric tag labeling strategy that allows (i) differentiation and (ii) enhanced relative quantification of lipid sn-positional isomers from distinct samples in a single run. The methodology enabled by aziridination, isobaric tag labeling, and lithiation has been applied to various phospholipids, enabling the determination of the sn-positions of fatty acyl chains and enhanced relative quantification. The analysis of Escherichia coli lipid extracts demonstrated the enhanced determination of the concentration ratios of lipid isomers by measuring the intensity ratios of mass reporters released from sn-positional diagnostic ions. Moreover, we applied the method to the analysis of human colon cancer plasma. Intriguingly, 17 PC lipid sn-positional isomers were identified and quantified simultaneously, and among them, 7 showed significant abundance changes in the colon cancer plasma, which can be used as potential plasma markers for diagnosis of human colon cancer.

Three-dimensional morphology scoring of hepatocellular carcinoma stratifies prognosis and immune infiltration.

BACKGROUND: The morphological attributes could serve as pivotal indicators precipitating early recurrence and dismal overall survival in hepatocellular carcinoma (HCC), and quantifying morphological features may better stratify the prognosis of HCC. OBJECTIVE: To develop a radiomics approach based on 3D tumor morphology features for predicting the prognosis of HCC and identifying differentially expressed genes related to morphology to guide HCC treatment. MATERIALS AND METHODS: Retrospective study of 357 HCC patients. Radiomic features were extracted from MRI tumor regions; 14 morphology-related features predicted early HCC recurrence and patient stratification via LASSO-Cox modeling. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. RNA sequencing from the Cancer Imaging Archive (TCIA) examined drug sensitivity and stratified HCC using morphological immunity genes, validating recurrence and prognosis. RESULTS: Patients were split into training (n = 225), test (n = 132), and 50 TCIA dataset cohorts. Two features (Maximum2DdiameterColumn, Sphericity) in Cox regression stratified patients into high/low-risk Morphological Radiological Score (Morph-RS) groups. Significant OS and RFS were seen across all sets. Differentially expressed genes focused on T cell receptor signaling; low-risk group had higher T cells (P = 0.039), B cells (P = 0.041), NK cells (P = 0.018). SN-38, GSK2126458 might treat high-risk morphology. Morphology-immune genes stratified HCC, showing significant RFS/OS differences. CONCLUSION: Tumor Morph-RS effectively stratifies HCC patients' recurrence and prognosis. Limited immune infiltration seen in Morph-RS high-risk groups signifies the potential of employing tumor morphology as a potent visual biomarker for diagnosing and managing HCC.

LI-RADS Morphological Type Predicts Prognosis of Patients with Hepatocellular Carcinoma After Radical Resection.

PURPOSE: This study aimed to explore the association of preoperative magnetic resonance imaging (MRI) tumor morphological classification with early recurrence (ER) and overall survival (OS) after radical surgery of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A retrospective analysis of 296 patients with HCC who underwent radical resection was performed. On the basis of LI-RADS, tumor imaging morphology was classified into three types. The clinical imaging features, ER, and survival rates of three types were compared. Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors associated with OS and ER after hepatectomy for HCC. RESULTS: There were 167 tumors of type 1, 95 of type 2, and 34 of type 3. In patients with type 3 HCC, postoperative mortality and ER were significantly higher than in patients with type 1 and type 2 (55.9% versus 32.6% versus 27.5% and 52.9% versus 33.7% versus 28.7%). In multivariate analysis, the LI-RADS morphological type was a stronger risk factor for predicting poor OS [hazard ratio (HR) 2.77, 95% confidence interval (CI) 1.59-4.85, P < 0.001] and ER (HR 2.14, 95% CI 1.24-3.70, P = 0.007). A subgroup analysis revealed that type 3 was associated with poor OS and ER in > 5 cm cases but not in < 5 cm cases. CONCLUSIONS: ER and OS of patients with HCC undergoing radical surgery can be predicted using the preoperative tumor LI-RADS morphological type, which could help to select personalized treatment plans for patients with HCC in the future.

Survival rate of colorectal cancer in China: A systematic review and meta-analysis.

Background: This study aims to comprehensively summarize the colorectal survival rate in China. Method: In PubMed and Web of Science, keywords such as "colorectal cancer", "survival" and "China" were used to search literatures in the past 10 years. Random effect models were selected to summarize 1-year, 3-year, and 5-year survival rates, and meta-regression and subgroup analyses were performed on the included studies. Results: A total of 16 retrospective and prospective studies providing survival rates for colorectal cancer in China were included. The 1-year, 3-year, and 5-year survival rates of colorectal cancer in China were 0.79, 0.72 and 0.62, respectively. In the included studies, the 5-year survival rates of stage I (5474 cases), stage II (9215 cases), stage III (8048 cases), and stage IV (4199 cases) colorectal cancer patients were 0.85, 0.81, 0.57 and 0.30, respectively. Among them, the 5-year survival rates of colorectal cancer were 0.82, 0.76, 0.71, 0.67, 0.66, 0.65 and 0.63 in Tianjin, Beijing, Guangdong, Shandong, Liaoning, Zhejiang and Shanghai, respectively. Conclusion: The 5-year survival rate in China is close to that of most European countries, but still lower than Japan and South Korea, and the gap is gradually narrowing. Region, stage, differentiation, pathological type, and surgical approach can affect 5-year survival in colorectal cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/ identifier, CRD42022357789.

Intrinsic resistance and efficacy of immunotherapy in microsatellite instability-high colorectal cancer: A systematic review and meta-analysis.

Some patients with microsatellite instability-high colorectal cancer (MSI-H CRC) have shown a poor response to immunotherapy in clinical trials. We investigated the intrinsic resistance to and efficacy of immunotherapy in patients with MSI-H CRC. The PubMed and Web of Science databases were searched using keywords such as "colorectal cancer," "immunotherapy," and "clinical experiment." Random-effects models were used to generate the combined complete response, partial response, stable disease, progressive disease, objective response rate (ORR), disease control rate (DCR), and incidence of adverse events. We then performed a subgroup analysis based on the ORR and incidence of intrinsic resistance. The meta-analysis included seven clinical trials. The incidences of complete response, partial response, stable disease, and progressive disease summarized by the random-effects model were 8%, 37%, 26%, and 25%, respectively. The ORR and DCR were 45% and 71%, respectively. The ORRs of programmed cell death protein 1 inhibitor (anti-PD-1), programmed death ligand 1 inhibitor (anti-PD-L1), and anti-PD-1 combined with cytotoxic T lymphocyte-associated antigen 4 inhibitor (anti-CTLA-4) immunotherapy were 38%, 54%, and 57%, respectively. The ORR of immune checkpoint inhibitors for first- and third-line therapy was 56% and 32%, respectively. Dual-drug immunotherapy significantly reduced the incidence of intrinsic resistance to immunotherapy (12% vs 31%). The incidences of intrinsic resistance to first-line therapy and second-line and later therapy were 29% and 26%, respectively. Approximately 25% of patients with MSI-H CRC had intrinsic resistance to immunotherapy. Anti-PD-1 combined with anti-CTLA-4 significantly increased the ORR, thereby reducing the incidence of intrinsic resistance. Moving immunotherapy into earlier lines of therapy, although not reducing the incidence of intrinsic resistance, can improve the ORR in patients with MSI-H CRC.

Real-world survival of colon cancer after radical surgery: A single-institutional retrospective analysis.

The survival rate for colon cancer after radical surgery has been the focus of extensive debate. To assess the postoperative survival and prognostic factors for overall survival (OS), we collected clinicopathological information for 2,655 patients. The survival time and potential risk factors for OS were analyzed by using Kaplan-Meier curves, Cox proportional hazards models, best subset regression (BSR), and least absolute shrinkage and selection operator (LASSO). The 5-year survival rates of stage I-IV colon cancer were 96.6%, 88.7%, 69.9%, and 34.3%, respectively. Adjuvant chemotherapy improved the survival rate (90.4% vs. 82.4%, with versus without adjuvant chemotherapy, respectively) in stage II patients with high-risk factors. Elevated preoperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were significantly associated with worse OS compared with patients without these elevations. Less than 12 versus more than 12 harvested lymph nodes (LNs) affected prognosis (84.6% vs. 89.7%, respectively). Regarding the lymph node ratio (LNR), the 5-year OS rate was 89.2%, 71.5%, 55.8%, and 34.5% in patients with LNR values of 0, 0.3, 0.3-0.7, and >0.7, respectively. We constructed a nomogram comprising the independent factors associated with survival to better predict prognosis. On the basis of these findings, we propose that stage II colon cancer patients without high-risk factors and with both elevated preoperative CEA and CA199 should receive adjuvant therapy. Furthermore, the LNR could complement TNM staging in patients with <12 harvested LNs. Our nomogram might be useful as a new prognosis prediction system for colon cancer patients.

Voltage-Controlled Divergent Cascade of Electrochemical Reactions for Characterization of Lipids at Multiple Isomer Levels Using Mass Spectrometry.

Cascading divergent reactions in a single system is highly desirable for their intrinsic efficiency and potential to achieve multilevel structural characterization of complex biomolecules. In this work, two electrochemical reactions, interfacial electro-epoxidation and cobalt anodic corrosion, are divergently cascaded in nanoelectrospray (nESI) and can be switched at different voltages. We applied these reactions to lipid identification at multiple isomer levels using mass spectrometry (MS), which remains a great challenge in structural lipidomics. The divergent cascade reactions in situ derivatize lipids to produce epoxidized lipids and cobalt-adducted lipids at different voltages. These lipids are then fragmented upon low-energy collision-induced dissociation (CID), generating diagnostic fragments to indicate C═C locations and sn-positions that cannot be achieved by the low-energy CID of native lipids. We have demonstrated that lipid structural isomers show significantly different profiles in the analysis of healthy and cancerous mouse prostate samples using this strategy. The application of divergent cascade reactions in lipid identification allows the four-in-one analysis of lipid headgroups, fatty acyl chains, C═C locations, and sn-positions simply by tuning the nESI voltages within a single experiment. This feature as well as its low sample consumption, no need for an extra apparatus, and quantitative analysis capability show its great potential in lipidomics.

Computational quantitative measures of Gd-EOB-DTPA enhanced MRI hepatobiliary phase images can predict microvascular invasion of small HCC.

PURPOSE: This study was designed to preoperatively predict microvascular invasion (MVI) of solitary small hepatocellular carcinoma (sHCC) by quantitative analysis of Gd-EOB-DTPA enhanced hepatobiliary phase (HBP) magnetic resonance imaging (MRI). METHOD: Sixty-one patients, 19 with and 42 without histologically confirmed MVI following hepatic resection for solitary sHCC (≤ 3 cm), were preoperatively examined with Gd-EOB-DTPA-enhanced MRI. The regions of interest (ROIs) of the hepatic lesions were manually delineated on the maximum cross-sectional area in the HBP images and used to calculate the lesion boundary index (LBI) and marginal gray changes (MGC). Histogram analysis was performed to measure standard deviations (STD) and coefficients of variation (CV). Correlations between quantitative parameters and MVI were evaluated and differences between MVI positive and negative groups were assessed. RESULTS: The average LBI (0.85 ± 0.07) and MGC (0.48 ± 0.27) values of the negative group were significantly higher (p < 0.05) than the corresponding LBI (0.72 ± 0.07) and MGC (0.28 ± 0.18) values of the positive group. STDs and CVs in the negative group were significantly smaller (p < 0.05) than those of the positive group. Receiver operating characteristic (ROC) analysis revealed that LBI had the best predictive value with an AUC, sensitivity, and specificity of 0.91, 87 %, and 80 %, respectively. CONCLUSIONS: Quantitative analysis of HBP images is useful for predicting MVI and beneficial to clinicians in making decisions before treatment.

A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules.

Background: A liquid biopsy using circulating exosomal genetic materials provides new insights for thyroid cancer diagnosis. This study aimed to identify plasma-derived exosomal biomarkers that could be used for early detection of papillary thyroid carcinoma (PTC). Method: Exosomal miRNAs in plasma were isolated from patients with benign thyroid nodules and patients with PTC. Profiling of exosomal miRNA was performed using RNA sequencing (RNA-seq) to identify miRNA candidates and differentiate the benign from malignant. The validation cohort consisted of 30 patients with benign thyroid nodules, 35 PTC patients, and 31 healthy individuals. Real-time PCR was used to quantify the expression of miRNA candidates. The diagnostic potential of the candidates was evaluated by receiver operating characteristic (ROC) curves. Results: After RNA-seq, eight plasma exosomal miRNAs were selected as candidates. Further validation indicated that the levels of exosomal miR-16-2-3p, miR-223-5p, miR-34c-5p, miR-182-5p, miR-223-3p, and miR-146b-5p were significantly lower in nodules compared to healthy controls (p < 0.0001), whereas miR-16-2-3p and miR-223-5p were significantly higher in the PTC cases than in those with benign nodules (p < 0.05). ROC analyses revealed that the above six miRNAs were potent indicators for detection of thyroid nodules. Meanwhile, miR-16-2-3p and miR-223-5p can be utilized for detecting PTC from benign nodules. Additionally, combined miRNA panels showed increased diagnostic sensitivities and specificities compared to single miRNA markers. Conclusion: Six aberrantly expressed plasma exosomal miRNAs may be used as diagnostic biomarkers to differentiate thyroid nodules from healthy individuals. The panel consisting of miR-16-2-3p, miR-223-5p, miR-101-3p, and miR-34c-5p are eligible for discriminating benign from malignant thyroid nodules.

The versatile roles and clinical implications of exosomal mRNAs and microRNAs in cancer.

Extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies, are nanosized structures that are secreted by various cells and act as important mediators in intercellular communication. Recent studies have shown that exosomes carrying bioactive molecules are generated from multivesicular bodies and are present in various body fluids. mRNAs and microRNAs (miRNAs) are encapsulated in exosomes and have been found to be involved in multiple pathophysiological processes. Here, we provide a review of tumor-associated exosomal mRNAs and miRNAs and their roles in metastasis and drug resistance. In particular, we emphasize their clinical application potential as diagnostic and prognostic biomarkers of cancer and in cancer therapy.

The prognostic value of preoperative fibrinogen-to-prealbumin ratio and a novel FFC score in patients with resectable gastric cancer.

BACKGROUND: Chronic inflammation is considered as a hallmark of gastric cancer (GC) and plays a critical role in GC progression and metastasis. This study aimed to explore the prognostic values of preoperative fibrinogen-to-prealbumin ratio (FPR), fibrinogen-to-albumin ratio (FAR), and novel FPR-FAR-CEA (FFC) score in patients with GC undergoing gastrectomy. METHODS: A total of 273 patients with resectable GC were included in this retrospective study. We performed Kaplan-Meier and Cox regression analyses to assess the prognostic role of preoperative FPR, FAR, and FFC score in patients with GC and analyze their relationships with clinicopathological features. RESULTS: Receiver operating characteristic curve (ROC) analysis revealed that the optimal cutoff values for FPR and FAR were 0.0145 and 0.0784, respectively. The FFC score had a higher area under the ROC curve than FAR and CEA. Elevated FPR (≥ 0.0145) and FAR (≥ 0.0784) were significantly associated with old age, large tumor size, tumor invasion depth, lymph nodes metastasis, advanced TNM stage, large Borrmann type, and anemia status. Kaplan-Meier analysis showed that high FPR, FAR, and FFC score were related to poor survival. Multivariate analyses indicated that FPR, FFC score, TNM stage, and tumor size were significant independent factors for survival. CONCLUSIONS: Preoperative FPR and FFC score could be used as prospective noninvasive prognostic biomarkers for resectable GC.

Combination of Four Serum Exosomal MiRNAs as Novel Diagnostic Biomarkers for Early-Stage Gastric Cancer.

Gastric cancer (GC) remains a leading cause of cancer-related mortality in the United States and China, there is an urgent need to discover novel non-invasive biomarkers for the early diagnosis of GC to improve the prognosis of GC patients. Exosomal miRNAs are considered promising biomarkers for cancer diagnosis. Using next-generation sequencing (NGS), bioinformatics and further validation, we identified and evaluated exosomal miRNAs in serum as early diagnostic markers for GC. NGS revealed that the average mappable reads in the RNA libraries were about 6.5 million per patient including miRNAs (73.38%), rRNAs (17.10%), snRNAs (8.83%), snoRNAs (0.65%), and tRNAs (0.04%). A total of 66 up and 13 down-regulated exosomal miRNAs were found in the screened cohort. In the validation cohort, by comparing with healthy individuals, higher levels of serum exosomal miR-92b-3p, let-7g-5p, miR-146b-5p, and miR-9-5p were found to be significantly associated with early-stage GC (p < 0.05). Diagnostic power of the combined panels of the exosomal miRNAs or the combination of exosomal miRNAs and CEA outperformed that of single exosomal miRNA marker for establishing a diagnosis of early-stage GC. The combined diagnosis of exosomal miR-92b-3p + let-7g-5p + miR-146b-5p + miR-9-5p with CEA had the most powerful efficiency with an AUC up to 0.786. In addition, serum levels of exosomal miR-92b-3p were significantly associated with poor cohesiveness (p = 0.0021), let-7g-5p and miR-146b-5p were significantly correlated with nerve infiltration (p = 0.0234 and p = 0.0126, respectively), and miR146b-5p was statistically correlated with tumor invasion depth in early-stage GC (p = 0.0089). In conclusion, serum exosomal miR-92b-3p, -146b-5p, -9-5p, and let-7g-5p may serve as potential non-invasive biomarkers for early diagnosis of GC.

LINC01559 accelerates pancreatic cancer cell proliferation and migration through YAP-mediated pathway.

Pancreatic cancer (PC) is one of the top two most fatal cancers, with the poorest survival rate among all human malignancies. Increasing evidence suggests the involvement of long noncoding RNAs (lncRNAs) in the initiation and progression of various cancers. Herein, we investigated the role of lncRNA LINC01559 in PC. Several online databases indicated that LINC01559 was at a low expression in normal pancreatic tissues but was obviously upregulated in PAAD tissues. Further, our results showed that LINC01559 was stimulated in PC cell lines relative to normal controls. Furthermore, we validated that LINC01559 facilitated PC cell proliferation and migration in vitro. Also, silencing LINC01559 obstructed PC cell growth in vivo. Besides, LINC01559 was revealed to be mainly in the cytoplasm of PC cells and therefore served as a ceRNA of Yes-associated protein (YAP) in PC cells via sponging miR-607. Surprisingly, we also proved that LINC01559 could interact with YAP protein, which might hinder YAP phosphorylation and enhance YAP transcriptional activity in PC cells. Furthermore, we demonstrated that YAP was the downstream effector in LINC01559-regulated PC development. Collectively, our findings unmasked that LINC01559 accelerates PC progression through relying on YAP, providing a new potential target for clinical treatment of patients with PC.

Interfacial Bonding and Abrasive Wear Behavior of Iron Matrix Composite Reinforced by Ceramic Particles.

Using zirconia toughened alumina (ZTA) particles and Ni-Ti complex powders as raw materials, high-Cr cast iron reinforced by ZTA particles was prepared by an infiltration casting process. A continuous transition layer formed at the interface between ZTA particles and the Cr15 matrix, which proves that there is strong metallurgical interfacial bonding at the interface. The phases in the Ni-Ti layer of the ZTAP/Fe composite were preserved compared with the microstructure of sintered ZTA ceramic preform. The hardness of the Ni3Ti, TiO and AlNi2Ti phases in the interfacial transition layer was measured by the nano-indentation method, which is 12.5 GPa, 16.1 GPa and 9.2 GPa, respectively. The three-body wear resistance of the composite reached 12.6 times that of high-Cr cast iron.

Combination of the preoperative albumin to globulin ratio and neutrophil to lymphocyte ratio as a novel prognostic factor in patients with triple negative breast cancer.

Background: The pretreatment albumin to globulin ratio (AGR) and neutrophil to lymphocyte ratio (NLR) were the inflammation-associated factors which were related to the disease-free survival in various malignancies. The aim of this study was to evaluate the clinical significance of the pretreatment AGR combined with NLR for patients with triple negative breast cancer (TNBC). Method: This retrospective study included 286 cases of pathologically diagnosed patients with TNBC. The relationships of AGR and NLR with clinicopathologic characteristics and prognosis were analyzed by Kaplan-Meier and Cox regression methods. Results: An AGR of 1.63 and a NLR of 2.93 were identified as the optimal cut-off points for distinguishing patients with good versus poor prognosis. The area under the receiver operating characteristic curves of combined with AGR and NLR (CO-AN) was increased compared with AGR and NLR individually. Kaplan-Meier analysis showed that low AGR/high NLR was related to poor survival. The prognosis of patients can be predicted well by the CO-AN. Univariate and multivariate analyses revealed that high AGR levels, low NLR levels, and CO-AN<1 were significantly and independently associated with favorable disease-free survival. Conclusions: Our study suggested that AGR and NLR levels can be prognostic biomarkers for disease-free survival in patients with TNBC. The CO-AN may have greater predictive value than AGR and NLR in patients with TNBC.

Gankyrin drives metabolic reprogramming to promote tumorigenesis, metastasis and drug resistance through activating ß-catenin/c-Myc signaling in human hepatocellular carcinoma.

Gankyrin plays important roles in tumorigenicity and metastasis of hepatocellular carcinoma (HCC). We have for the first time investigated the effects of Gankyrin on glycolysis and glutaminolysis both in vitro and in vivo, including in patient-derived xenografts. We reported Gankyrin increases glucose consumption, lactate production, glutamine consumption and glutamate production in HCC through upregulating the expression of the transporters and enzymes involved in glycolysis and glutaminolysis, including HK2, GLUT1, LDHA, PKM2, ASCT2 and GLS1. We further demonstrated that Gankyrin drives glycolysis and glutaminolysis through upregulating c-Myc via activating ß-catenin signaling. Importantly, we found c-Myc mediated metabolic reprogramming might contribute to the tumorigenicity, metastasis and drug resistance induced by Gankyrin. c-Myc inhibitor synergizes with Sorafenib or Regorafenib to suppress HCC PDX tumors with high Gankyrin levels. We detected a significant correlation between Gankyrin and ß-catenin expression levels in a cohort of HCC biopsies, and combination of these two parameters is a more powerful predictor of poor prognosis. Collectively, our results uncovered that Gankyrin functions as an essential regulator in glycolysis and glutaminolysis via activation of ß-catenin/c-Myc to promotes tumorigenesis, metastasis and drug resistance in human HCC.