Photoactivated Formation of an Extravascular Dynamic Hydrogel as an Intelligent Blood Flow Regulator to Reprogram the Immunogenic Landscape.

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.

Thioredoxin facilitates hepatocellular carcinoma stemness and metastasis by increasing BACH1 stability to activate the AKT/mTOR pathway.

Thioredoxin (TXN) is essential for preserving balance and controlling the intracellular redox state. Most studies have focused on the function of TXN in redox reactions, which is critical for tumor progression. Here, we showed that TXN promotes hepatocellular carcinoma (HCC) stemness properties in a non-redox-dependent manner, which has rarely been reported in previous studies. TXN exhibited upregulated expression in human HCC specimens, which was associated with a poor prognosis. Functional studies showed that TXN promoted HCC stemness properties and facilitated HCC metastasis both in vitro and in vivo. Mechanistically, TXN promoted the stemness of HCC cells by interacting with BTB and CNC homology 1 (BACH1) and stabilized BACH1 expression by inhibiting its ubiquitination. BACH1 was positively correlated with TXN expression and was significantly upregulated in HCC. In addition, BACH1 promotes HCC stemness by activating the AKT/mammalian target of rapamycin (mTOR) pathway. Furthermore, we found that the specific inhibition of TXN in combination with lenvatinib in mice significantly improved the treatment of metastatic HCC. In summary, our data demonstrate that TXN plays a crucial role in HCC stemness and BACH1 plays an integral part in regulating this process by activating the AKT/mTOR pathway. Thus, TXN is a promising target for metastatic HCC therapy.

Drug-related adverse events potentially predict the efficacy of apatinib on advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide every year, and most HCC patients are diagnosed with advanced disease and can only receive systemic treatment. TKIs are the most important components of the systemic treatment of HCC and have both good efficacy and adverse events (AEs).  METHODS: This analysis included 207 patients with locally advanced unresectable or metastatic HCC who received oral treatment with apatinib. We analyzed the overall survival (OS) and progression-free survival (PFS) of patients with or without corresponding AEs to evaluate which AEs can predict the efficacy of apatinib. RESULTS: Patients with hand-foot syndrome (HFS; p = 0.005), proteinuria (p = 0.006) and diarrhea (p < 0.001) had significantly better OS than those without corresponding AEs, and the appearance of HFS (p = 0.006) and proteinuria (p = 0.004) was associated with longer PFS. CONCLUSION: Among all the AEs induced by apatinib in the treatment of advanced HCC, proteinuria could potentially predict PFS, and diarrhea was a potential predictor of OS.

Upregulation of CRABP2 by TET1-mediated DNA hydroxymethylation attenuates mitochondrial apoptosis and promotes oxaliplatin resistance in gastric cancer.

Oxaliplatin is the main chemotherapy drug for gastric cancer (GC), but quite a few patients are resistant to oxaliplatin, which contributes to the poor prognosis of GC patients. There is therefore an urgent need to identify potential targets for reversing chemotherapy resistance in GC patients. In this study, we analyzed the tumor samples of GC patients who received neoadjuvant chemotherapy based on oxaliplatin through quantitative proteomics and identified the potential chemoresistance-related protein cellular retinoic acid binding protein 2 (CRABP2). CRABP2 was significantly upregulated in the tumor tissues of chemoresistant GC patients and was closely related to prognosis. The results of cell function experiments showed that CRABP2 can promote the oxaliplatin resistance of GC cells in vitro. Coimmunoprecipitation and GST pulldown assays showed that CRAPB2 expedited the binding of BAX and PARKIN in GC cells and facilitated the ubiquitination-mediated degradation of BAX. Furthermore, both the in vitro assay and cell-derived xenograft (CDX) in vivo model verified that CRABP2 promoted oxaliplatin resistance by inhibiting BAX-dependent cell apoptosis. Further experiments proved that the abnormally high expression of CRABP2 in oxaliplatin-resistant GC cells was affected by TET1-mediated DNA hydroxymethylation. The patient-derived xenograft (PDX) model suggested that interference with CRABP2 reversed oxaliplatin resistance in GC in vivo. In conclusion, the results of our study show that CRABP2 was a key molecule in oxaliplatin resistance regulation and could be a new target for reversing the chemoresistance of GC.

Microwave Synthesized 2D WO3 Nanosheets for VOCs Gas Sensors.

As an n-type semiconductor material, tungsten oxide (WO3) has good application prospects in the field of gas sensing. Herein, using oxalic acid (OA), citric acid (CA) and tartaric acid (TA) as auxiliary agents, three homogeneous tungsten oxide nanosheets were prepared by the rapid microwave-assisted hydrothermal method. The potential exhaled gases of various diseases were screened for the gas sensitivity test. Compared with WO3-OA and WO3-TA, WO3-CA exhibits significant sensitivity to formaldehyde, acetone and various alkanes. Photoluminescence (PL) chromatography and photoelectric properties show that its excellent gas sensitivity is due to its abundant oxygen vacancies and high surface charge migration rate, which can provide more preferential reaction sites with gas molecules. The experiment is of great significance for the sensor selection of the large disease exhaled gas sensor array.

Size-changeable nanoprobes for the combined radiotherapy and photodynamic therapy of tumor.

PURPOSE: Radiation therapy (RT) and photodynamic therapy (PDT) are promising while challenging in treating tumors. The potential radiation resistance of tumor cells and side effects to healthy tissues restrict their clinical treatment efficacy. Effective delivery of therapeutic agents to the deep tumor tissues would be available for tumor-accurate therapy and promising for the tumor therapy. Thus, developing nanoprobes with effectively delivering radiotherapy sensitizers and photosensitizers to the interior of tumors is needed for the accurate combined RT and PDT of tumor. METHODS: The size-changeable nanoprobes of Gd2O3@BSA-BSA-Ce6 (BGBC) were synthesized with a crosslinking method. Magnetic resonance imaging (MRI) and in vivo near-infrared (NIR) imaging were measured to evaluate the nanoprobes' tumor accumulation and intratumor penetration effect. The tumor suppression effect of combined RT and PDT with these nanoprobes was also studied for the 4T1 bearing Balb/c mice. RESULTS: The nanoprobes BGBC showed high tumor accumulation and disintegrated into small particles responding to the photo-irradiation-produced reactive oxygen species (ROS), allowing for tumor penetration. Abundant radiotherapy sensitizers and photosensitizers were delivered to the deep tumor tissues, which is available for the accurate therapy of tumor. In addition, the BGBC displayed outstanding MRI and fluorescence imaging effects for evaluating the biodistribution and tumor suppression effect of nanoprobes. Consequently, significant tumor suppression effect was obtained based on the accurate tumor treatment with the combined RT and PDT. CONCLUSION: The designed size-changeable nanoprobes BGBC showed excellent tumor accumulation and deep tumor penetration, resulting in a significant tumor suppression effect based on the combined RT and PDT. This study provides a novel strategy for dual delivery of radiotherapy sensitizers and photosensitizers into the deep tumor tissues and is promising for the accurate theranostics of tumor.

Biodegradable Metal-Organic-Framework-Gated Organosilica for Tumor-Microenvironment-Unlocked Glutathione-Depletion-Enhanced Synergistic Therapy.

The clinical employment of cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) is largely constrained due to the non-specific delivery and resultant serious systemic toxicity. Small-sized biocompatible and biodegradable hollow mesoporous organosilica (HMOS) nanoparticles show superior advantages for targeted CDDP delivery but suffer from premature CDDP leakage. Herein, the smart use of a bimetallic Zn2+ /Cu2+ co-doped metal-organic framework (MOF) is made to block the pores of HMOS for preventing potential leakage of CDDP and remarkably increasing the loading capacity of HMOS. Once reaching the acidic tumor microenvironment (TME), the outer MOF can decompose quickly to release CDDP for chemotherapy against cancer. Besides, the concomitant release of dopant Cu2+ can deplete the intracellular glutathione (GSH) for increased toxicity of CDDP as well as catalyzing the decomposition of intratumoral H2 O2 into highly toxic •OH for chemodynamic therapy (CDT). Moreover, the substantially reduced GSH can also protect the yielded •OH from scavenging and thus greatly improve the •OH-based CDT effect. In addition to providing a hybrid HMOS@MOF nanocarrier, this study is also expected to establish a new form of TME-unlocked nanoformula for highly efficient tumor-specific GSH-depletion-enhanced synergistic chemotherapy/chemodynamic therapy.

The Neutrophil-to-Lymphocyte Ratio (NLR) Predicts the Prognosis of Unresectable Intermediate and Advanced Hepatocellular Carcinoma Treated with Apatinib.

PURPOSE: Patients with hepatocellular carcinoma (HCC) who might benefit most from anti-angiogenesis therapy remain unknown. In recent years, neutrophil-to-lymphocyte ratio (NLR), an indicator of inflammatory response, has received particular attention in HCC. Herein, we explored the prognostic value of pre-treatment NLR in individuals with unresectable intermediate and advanced hepatocellular carcinoma treated with apatinib, a second-line angiogenesis inhibitor. The findings of this study would assist in precision medicine and provide clinical decision support. PATIENTS AND METHODS: This is a retrospective study in which 171 HCC patients attending Tianjin Medical University Cancer Institute and Hospital and treated with apatinib between January 2016 and July 2018 were enrolled. The prognosis of the patients based on NLR signatures was then analyzed. RESULTS: Patients with a low pre-treatment NLR (NLR < 2.49) presented a significantly longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.043). Furthermore, a low pre-treatment NLR level could be used to predict a longer OS in patients with non-macrovascular invasion (P < 0.001). Independent of serum alpha-fetoprotein (AFP) levels, a low NLR level in this cohort of patients is associated with a longer OS. CONCLUSION: Pre-treatment NLR predicts the prognosis of patients with unresectable intermediate and advanced HCC treated with apatinib.

Angiotensin-converting enzyme inhibitors have adverse effects in anti-angiogenesis therapy for hepatocellular carcinoma.

At present, anti-angiogenic drugs (AADs) are widely used in the systemic treatment of hepatocellular carcinoma (HCC) or other types of cancer, and have achieved good anti-cancer effect, whereas treatment-related proteinuria can affect the routine use of AADs, which in turn abates the overall efficacy. Currently, most clinicians prescribe angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria according to diabetic nephropathy guidelines or expert recommendations. However, the efficacy of ACEIs in reducing AAD-related proteinuria and its effect on the anticancer effect of AADs is unknown. Our clinical data showed that some HCC patients experienced tumor progression by ACEIs administration for the treatment of proteinuria caused by AADs. Here, we confirmed that in different tumor-bearing mouse models, ACEIs did not delay the appearance of proteinuria or alleviate proteinuria caused by AADs but compromised the anticancer efficacy of AADs. This effect is unrelated to the change in the VEGF signaling pathway. Our data showed that the combination of ACEIs and AADs flared the production of kidney-derived erythropoietin (EPO). In turn, EPO compromises the anti-angiogenic effects of AADs and decreases antitumor activity. In conclusion, for the treatment of proteinuria caused by AADs, ACEIs have no efficacy while also promoting AADs resistance. This finding is of great significance to guide clinical standardized management of side effects of anti-angiogenic therapy for cancer patients.

Radioiodinated Persistent Luminescence Nanoplatform for Radiation-Induced Photodynamic Therapy and Radiotherapy.

Radionuclide with Cerenkov radiation (CR) can serve as an internal excitation source to activate photosensitizers for photodynamic therapy (PDT) in deep tumor. However, the low efficiency of CR limits its therapeutic efficacy. A 131 I labeled zinc tetra(4-carboxyphenoxy) phthalocyaninate (ZnPcC4) conjugated Cr3+ -doped zinc gallate (ZnGa2 O4 :Cr3+ , ZGCs) nanoplatform (131 I-ZGCs-ZnPcC4) is developed for radiotherapy (RT) and radiation-induced PDT. 131 I can not only activate ZGCs for long-lasting luminescence via both Cerenkov luminescence (CL) and ionizing radiation, which further continuously activate photosensitizer ZnPcC4 for PDT, but also can directly kill cancerous cells. This 131 I-ZGCs-ZnPcC4 exhibits excellent tumor inhibition both in vitro and in vivo. Combining self-activated PDT and RT, it is believed that the 131 I-ZGCs-ZnPcC4 can greatly benefit the deep tumor therapy.

Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial.

BACKGROUND: The prognosis for advanced hepatocellular carcinoma (HCC) remains clinically unsatisfying. Apatinib has proven to be a very effective treatment for advanced HCC in our previous retrospective study. Our aim in this study was to evaluate the efficacy, safety, and toxicity of apatinib in patients with advanced HCC. METHODS: This single-arm, open-label phase II clinical trial enrolled patients with advanced HCC. These patients received apatinib, 500 mg once daily, until disease progression, unacceptable toxicity, consent withdrawal, or death. One treatment cycle consisted of 4 weeks of apatinib treatment. The response evaluation criteria in solid tumors (RECIST) was used to assess tumor response every 1-2 cycles. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and toxicity. RESULTS: Between December 2016 and June 2018, 23 patients were enrolled in the study, 22 of whom were available for response evaluation. The cutoff date was August 10, 2018. The overall ORR and DCR were 30.4% and 65.2%, respectively. The median OS and PFS were 13.8 (95% CI: 5.3-22.3) and 8.7 (95% CI: 5.9-11.1) months, respectively. The most common treatment-related adverse events were proteinuria (39.1%), hypertension (34.8%), and hand-foot-skin reaction (34.8%). CONCLUSIONS: Apatinib showed robust clinical activity in patients with advanced HCC. Moreover, apatinib was safe to use, well tolerated, and had acceptable toxicity. (NCT03046979).

In Vivo Repeatedly Activated Persistent Luminescence Nanoparticles by Radiopharmaceuticals for Long-Lasting Tumor Optical Imaging.

Persistent luminescence nanoparticles (PLNPs) with rechargeable near-infrared afterglow properties attract much attention for tumor diagnosis in living animals since they can avoid tissue autofluorescence and greatly improve the signal-to-background ratio. Using UV, visible light, or X-ray as excitation sources to power up persistent luminescence (PL) faces the challenges such as limited tissue penetration, inefficient charging capability, or tissue damage caused by irradiation. Here, it is proved that radiopharmaceuticals can efficiently excite ZnGa2 O4 :Cr3+ nanoparticles (ZGCs) for both fluorescence and afterglow luminescence via Cerenkov resonance energy transfer as well as ionizing radiation. 18 F-FDG, a clinically approved tumor-imaging radiopharmaceutical with a short decay half-life around 110 min, is successfully used as the internal light source to in vivo excite intravenously injected ZGCs for tumor luminescence imaging over 3 h. The luminescence with similar decay time can be re-obtained for multiple times upon injection of 18 F-FDG at any time needed with no health concern. It is believed this strategy can not only provide tumor luminescence imaging with high sensitivity, high contrast, and long decay time at desired time, but also guarantee the patients much less radiation exposure, greatly benefiting image-guided surgery in the future.

Drug-Related Hypertension Associated with the Efficacy of Apatinib on Hepatocellular Carcinoma.

PURPOSE: We retrospectively evaluated the efficacy and safety of apatinib as a first-line treatment for advanced hepatocellular carcinoma (HCC) and explored whether drug-related hypertension (HTN) could predict its efficacy. PATIENTS AND METHODS: This retrospective analysis included patients with advanced HCC who received oral treatment with apatinib. We evaluated the effectiveness by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease control rate (DCR), and assessed the safety of the drug based on the occurrence of adverse events. In order to explore whether apatinib-related HTN can be used as a predictor of therapeutic effect, patients were divided into an HTN group and a non-HTN group and adjusted for propensity score-matched (PSM) to reduce mixed deviation. Subgroup analyses of negative prognostic factors for advanced HCC were also performed, including alpha-fetoprotein (AFP), Child-Pugh Score, macrovascular invasion, and extrahepatic metastasis. RESULTS: A total of 208 patients were analyzed, of which 40.9% (n =85) developed drug-related HTN. For all patients, the OS was 13.4 months (95% CI, 12.2-14.6), the PFS was 5.7 months (95% CI, 5.1-6.3), and the TTP was 6.9 months (95% CI, 6.0-7.8). The OS of the HTN group and the non-HTN group was 17.4 months (m) and 12.5m (p=0.001), and the PFS was 7.4m and 4.7m (p=0.000), respectively. After PSM, the OS (p=0.001) and PFS (p=0.003) of the HTN group were still significantly better than the non-HTN group. Subgroup analysis suggested that overall survival was significantly longer in patients with HTN when serum AFP ≤400 µg/L or extrahepatic metastases. Moreover, OS in the HTN group increased significantly with or without macrovascular invasion. In addition, through the analysis of two groups of patients with PFS>6m and PFS≤6m, we know that the patients with drug-related HTN may develop resistance later, so they have longer survival time. CONCLUSION: Apatinib demonstrates compelling anti-cancer activity and acceptable safety in advanced HCC. Apatinib-related HTN can potentially predict prolonged survival in patients with advanced HCC.

Resection of "down-staged" advanced hepatocellular carcinoma after treatment with the VEGFR2 inhibitor apatinib: five cases report.

Sorafenib and lenvatinib are currently standard treatments for advanced hepatocellular carcinoma (HCC); however, the therapeutic effect is unsatisfying. Indeed, very few patients with HCC under sorafenib treatment were eligible for surgery in the past ten years. In addition, there is no report of a patient with the opportunity to undergo radical resection after treatment with lenvatinib. Here, we describe five patients with advanced and unresectable HCC that were able to receive curative resection within 1 year of treatment with the tyrosine kinase inhibitor apatinib that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR2). The five patients with advanced and unresectable HCC were treated with apatinib (250 mg po, qd), and all the five patients obtained an objective response to the treatment, allowing for subsequent resection, and the second patient even obtained a pathological complete response. The latest follow-up date was August 20, 2019, and all patients were alive at the latest follow-up. The disease-free survival of the first patient was 13 months. Lung metastasis was found 12 months later after surgery for patient 5. The other three patients have no recurrence. This is the first report of a single drug with promising therapeutic effects in patients with advanced HCC within one year at a single center. Therefore, apatinib may be promising for some patients with locally advanced HCC to undergo radical resection and improve outcomes.

Down-expression of poly(ADP-ribose) polymerase in p53-regulated pancreatic cancer cells.

The present study investigated whether poly(ADP-ribose) polymerase (PARP) has an effect on p53-regulated pancreatic cancer. The results of the present study demonstrated that the expression of PARP affects proliferation and apoptosis of pancreatic cancer cells. Olaparib was used to suppress the expression level of PARP-1 in PanC-1 cells. Decreased expression of PARP-1 suppressed cell proliferation and induced apoptosis of PanC-1 cells when compared with controls. Furthermore, decreased expression of PARP-1 resulted in decreased levels of pro-caspase-3 expression, increased caspase-3 activity, suppressed B-cell lymphoma 2 (Bcl-2) protein expression and increased p53 protein expression in PanC-1 cells. Subsequently, ataxia telangiectasia mutated (ATM) activity was inhibited alongside down-expression of PARP-1 resulting in significantly decreased cellular viability of PanC-1 cells, increased p53 protein expression, decreased expression of pro-caspase-3, increased caspase-3 activity and suppressed Bcl-2 protein expression, when compared with PARP-1 suppression alone. Overall, the in vitro data confirmed that down-expression of PARP-1 suppressed cell proliferation and induced apoptosis of pancreatic cancer via ATM-deficient p53 signaling pathway.

Apatinib is effective for treatment of advanced hepatocellular carcinoma.

As treatment options for hepatocellular carcinoma (HCC) are currently limited, we evaluated the efficacy and safety of oral apatinib, a VEGFR-2 inhibitor, on patients with advanced HCC. Twenty-two patients from Tianjin Medical University Cancer Institute and Hospital were enrolled for evaluation. Apatinib was administered at 500 mg/day or 250 mg/day continuously. Clinical endpoints were time to disease progression (TTP), overall survival (OS), and safety. The median TTP of treated patients was 10.4 months (95% CI 3.4 -17.5). At the last follow-up, 50% patients had survived longer than 11.4 months from the first dose. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates were 0%, 40.9%, 40.9%, and 18.2%, respectively. The most common apatinib-related adverse events were hand-foot skin reaction (HFSR) (81.8%) and diarrhea (77.3%). Hypertension (27.3%) and HFSR (13.6%) were the most frequent grade 3/4 adverse events. In summary, results of this small study indicate that apatinib is well tolerated and extremely effective for the treatment of advanced HCC. It is therefore imperative to design and carry out well-controlled clinical trials to confirm its efficacy.

Exploration of the value of MRCP combined with tumor marker CA19-9 in the diagnosis of pancreatic cancer.

This paper aims to provide an effective, accurate, and specific diagnostic method for the diagnosis of pancreatic cancer. It discusses the diagnostic value of magnetic res retrograde cholangiopancreatography (MRCP) combined with the detection of tumor marker carbohydrate antigen 19-9 (CA19-9) for pancreatic cancer. A group of confirmed cases of pancreatic cancer in some hospitals were randomly selected and subjected to an MRCP examination as well as serological CA19-9 detection. In addition, a group of patients whose pancreatic cancer was confirmed by surgery and pathology, and who underwent MRCP without the detection of the tumor marker CA19-9, were also selected for research. The experiment found that the rate of accuracy for the group that underwent MRCP combined with CA19-9 detection showed a higher positive value in the diagnosis of pancreatic cancer than in the group that underwent MRCP alone. Therefore, this paper proposes that MRCP combined with CA19-9 detection can be taken as the reliable and effective means for diagnosis of pancreatic cancer.

Correlation and malignant transformation of MSCs with the overexpression of SIL-R/GP130 under the tumor microenvironment.

Mesenchymal stem cells (MSCs) can differentiate into chondrogenesis, osteogenesis, myocardium and nerve in specific conditions, but it may undergo malignant transformation when cultivated with tumor cells. This research was to provide preliminary experimental basis for the safe application of MSCs and seek for drugs to avoid the malignant transformation of MSCs in the treatment of tumor. Accordingly, four groups including experimental group, positive control group, negative contrast group and blank group were set. Experimental group was the co-culture group of MSCs and C6 glioma cells. Positive control group was the regular culture group of C6 glioma cells. Negative control group was the co-culture group of MSCs and astrocyte. And blank group was the regular culture group of MSCs. The results showed the expression of IL-6, and IL-6R significantly increased in the group of co-culture with C6; the proliferation situation of MSCs was obviously strengthened; MSCs performed a high expression of GP130, STAT-3, CyclinD1 and BCL-xl, which had statistical significance compared with the contrast group. It can be concluded that the malignant expression of MSCs was related to the overexpression and activation of SIL-R/GP130; and the excessive expression and activation of SIL-6R and GP130 might be one of the important reasons for malignant transformation of MSCs under the microenvironment.

XAGE-1b expression is associated with the diagnosis and early recurrence of hepatocellular carcinoma.

XAGE-1b is a 470 bp transcript of the XAGE-1 gene, which belongs to the cancer-testis antigens that exhibit a restricted pattern of expression in normal tissues. Recently, the expression of XAGE-1b has been shown to be frequent in patients with hepatocellular carcinoma (HCC). However, the underlying mechanism is not fully understood. To investigate the role of XAGE-1b in HCC diagnosis and postoperative evaluation, the expression level of XAGE-1b was first examined in the tissue and peripheral blood of HCC patients and controls by using quantitative polymerase chain reaction. Subsequently, the associations between XAGE-1b and the clinical variables were assessed using χ2 or Kaplan-Meier tests. The data showed that HCC tissues had increased XAGE-1b expression when compared to paired non-tumorous tissues. The blood samples from the HCC patients showed upregulated XAGE-1b mRNA, as compared to non-HCC patients. The patients with portal vein tumor thrombus or higher tumor-node metastasis stages (II~IV) were more likely to have increased levels of XAGE-1b mRNA. Furthermore, the 1-year recurrence rate of the patients with a high level of XAGE-1b mRNA was significantly greater compared to the patients with a low level. All these findings indicate that XAGE-1b is associated with the aggressive biological behavior of HCC cells and it may be a potential biomarker for HCC diagnosis and prognosis.