Research progress of ginger in the treatment of gastrointestinal tumors.

Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors.

Exploring the targets and molecular mechanism of glycyrrhetinic acid against diabetic nephropathy based on network pharmacology and molecular docking.

BACKGROUND: Diabetic nephropathy (DN) stands as the most prevalent chronic microvascular complication of diabetes mellitus. Approximately 50% of DN patients progress to end-stage renal disease, posing a substantial health burden. AIM: To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid (GA) treats DN, subsequently validating these predictions through experimental means. METHODS: The study initially identified GA targets using Pharm Mapper and the TCMSP database. Targets relevant to DN were obtained from the Genecards, OMIM, and TTD databases. The Venny database facilitated the acquisition of intersecting targets between GA and DN. The String database was used to construct a protein interaction network, while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis. Molecular docking experiments were performed using Autodock software with selected proteins. Experimental validation was conducted using renal proximal tubular cells (HK-2) as the study subjects. A hyperglycemic environment was simulated using glucose solution, and the effect of GA on cell viability was assessed through the cell counting kit-8 method. Flow cytometry was employed to detect cell cycle and apoptosis, and protein immunoblot (western blot) was used to measure the expression of proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and insulin resistance pathway, including insulin receptor (INSR), PI3K, p-PI3K, AKT, p-AKT, and glycogen synthase kinase-3 (GSK3). RESULTS: A total of 186 intersecting targets between GA and DN were identified, which were associated with 144 KEGG-related enrichment pathways, 375 GO biological process entries, 45 GO cellular component entries, and 112 GO cellular function entries. Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase (MAPK)-1, SRC, PIK3R1, HSP90AA1, CASPASE9, HARS, KRAS, and MAPK14. In vitro experiments revealed that GA inhibited HK-2 cell viability, induced cell cycle arrest at the G2/M phase, and reduced apoptosis with increasing drug concentration. Western blot analysis showed that GA differentially up-regulated GSK3 protein expression, up-regulated AKT/p-AKT expression, down-regulated INSR, AKT, p-AKT, PI3K, and p-PI3K protein expression, and reduced p-PI3K/PI3K levels under high glucose conditions. CONCLUSION: GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway, thereby inhibiting HK-2 cell viability, reducing HK-2 cell apoptosis, and inducing cell cycle arrest at the G0/G1 phase.

MiR-204-3p overexpression inhibits gastric carcinoma cell proliferation by inhibiting the MAPK pathway and RIP1/MLK1 necroptosis pathway to promote apoptosis.

BACKGROUND: Gastric carcinoma (GC) is the third most frequent cause of cancer-related death, highlighting the pressing need for novel clinical treatment options. In this regard, microRNAs (miRNAs) have emerged as a promising therapeutic strategy. Studies have shown that miRNAs can regulate related signaling pathways, acting as tumor suppressors or tumor promoters. AIM: To explore the effect of miR-204-3p on GC cells. METHODS: We measured the expression levels of miR-204-3p in GC cells using quantitative real-time polymerase chain reaction, followed by the delivery of miR-204-3p overexpression and miR-204-3p knockdown vectors into GC cells. CCK-8 was used to detect the effect of miR-204-3p on the proliferation of GC cells, and the colony formation ability of GC cells was detected by the clonal formation assay. The effects of miR-204-3p on GC cell cycle and apoptosis were detected by flow cytometry. The BABL/c nude mouse subcutaneous tumor model using MKN-45 cells was constructed to verify the effect of miR-204-3p on the tumorigenicity of GC cells. Furthermore, the study investigated the effects of miR-204-3p on various proteins related to the MAPK signaling pathway, necroptosis signaling pathway and apoptosis signaling pathway on GC cells using Western blot techniques. RESULTS: Firstly, we found that the expression of miR-204-3p in GC was low. When treated with the lentivirus overexpression vector, miR-204-3p expression significantly increased, but the lentivirus knockout vector had no significant effect on miR-204-3p. In vitro experiments confirmed that miR-204-3p overexpression inhibited GC cell viability, promoted cell apoptosis, blocked the cell cycle, and inhibited colony formation ability. In vivo animal experiments confirmed that miR-204-3p overexpression inhibited subcutaneous tumorigenesis ability in BABL/c nude mice. Simultaneously, our results verified that miR-204-3p overexpression can inhibit GC cell proliferation by inhibiting protein expression levels of KRAS and p-ERK1/2 in the MAPK pathway, as well as inhibiting protein expression levels of p-RIP1 and p-MLK1 in the necroptosis pathway to promote the BCL-2/BAX/Caspase-3 apoptosis pathway. CONCLUSION: MiR-204-3p overexpression inhibited GC cell proliferation by inhibiting the MAPK pathway and necroptosis pathway to promote apoptosis of GC cells. Thus, miR-204-3p may represent a new potential therapeutic target for GC.

Anti-tumor effect of coix seed based on the theory of medicinal and food homology.

Coix seed is a dry and mature seed of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf in the Gramineae family. Coix seed has a sweet, light taste, and a cool nature. Coix seed enters the spleen, stomach, and lung meridians. It has the effects of promoting diuresis and dampness, strengthening the spleen to prevent diarrhea, removing arthralgia, expelling pus, and detoxifying and dispersing nodules. It is used for the treatment of edema, athlete's foot, poor urination, spleen deficiency and diarrhea, dampness and obstruction, lung carbuncle, intestinal carbuncle, verruca, and cancer. The medicinal and health value is high, and it has been included in the list of medicinal and food sources in China, which has a large development and application space. This article reviews the current research achievements in the processing methods and anti-tumor activities of Coix seed and provides examples of its clinical application in ancient and modern times, aiming to provide reference for further research on Coix seed and contribute to its clinical application and development. Through the analysis of the traditional Chinese patent medicines, and simple preparations and related health food of Coix seed queried by Yaozhi.com, the source, function, and dosage form of Coix seed were comprehensively analyzed, with a view of providing a reference for the development of Coix seed medicine and food.

Sorafenib inhibits proliferation and invasion of human hepatocellular carcinoma cells via up-regulation of p53 and suppressing FoxM1.

AIM: Forkhead box M1 (FoxM1) is a transcription factor that plays important roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). The aim of this study was to examine the involvement of FoxM1 in the anti-cancer action of sorafenib, a multikinase inhibitor, in human HCC cells. METHODS: HCC cell lines HepG2 and HuH-7 were tested. Cell viability was examined using MTT assay and cell invasion was determined with Transwell migration assay. The relevant mRNA expression was determined with RT-PCR, and the proteins were detected using Western blotting and immunofluorescence assays. RNA interference was used to modify the expression of p53 and FoxM1. HuH-7 cell line xenograft mice were used for in vivo study, which were treated with sorafenib (40 mg/kg, po) daily for 3 weeks. RESULTS: Sorafenib (2-20 µmol/L) inhibited the proliferation of the cells in dose- and time-dependent manners with an IC50 value of nearly 6 µmol/L at 48 h. Sorafenib (6 µmol/L) markedly suppressed the cell invasion. Furthermore, sorafenib (2-6 µmol/L) dose-dependently decreased the expression of FoxM1, MMP-2, and Ki-67, and up-regulated that of p53 in the cells. Silencing p53 abolished the decrease of FoxM1 and increase of p53 in sorafenib-treated cells. Silencing FoxM1 significantly reduced the expression of MMP-2 and Ki-67, and enhanced the anti-proliferation action of sorafenib in the cells, whereas overexpression of FoxM1 increased the expression of MMP-2 and Ki-67, and abrogated the anti-proliferation action of sorafenib. In the xenograft mice, sorafenib administration decreased the tumor growth by 40%, and markedly increased the expression of p53, and decreased the expression of FoxM1, MMP-2, and Ki-67 in tumor tissues. CONCLUSION: Sorafenib inhibits HCC proliferation and invasion by inhibiting MMP-2 and Ki-67 expression due to up-regulation of P53 and suppressing FoxM1.

FoxM1 overexpression promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma.

AIM: To investigate the expression of forkhead box protein M1 (FoxM1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma (HCC) and its role in metastasis. METHODS: FoxM1 and E-cadherin expression in HCC tissue microarray specimens was evaluated by immunohistochemical staining, and statistical methods were applied to analyze the correlation between FoxM1 and epithelial-mesenchymal transition (EMT). Kaplan-Meier analysis of the correlation between the FoxM1 expression level and recurrence or overall survival of HCC patients was performed. The expression of FoxM1, E-cadherin and snail homologue 1 (SNAI1) in HCC cell lines was evaluated by real-time reverse transcription-polymerase chain reaction and Western blot. Hepatocyte growth factor (HGF) was used to induce EMT and stimulate cell migration in HCC cells. The expression of FoxM1 and SNAI1 was regulated by transfection with plasmids pcDNA3.1 and siRNAs in vitro. The occurrence of EMT was evaluated by Transwell assay, morphologic analysis and detection of the expression of EMT markers (E-cadherin and vimentin). Luciferase and chromatin immunoprecipitation assays were used to evaluate whether SNAI1 is a direct transcriptional target of FoxM1. RESULTS: FoxM1 expression was increased significantly in HCC compared with para-carcinoma (10.7 ± 0.9 vs 8.2 ± 0.7, P < 0.05) and normal hepatic (10.7 ± 0.9 vs 2.7 ± 0.4, P < 0.05) tissues. Overexpression of FoxM1 was correlated with HCC tumor size, tumor number, macrovascular invasion and higher TNM stage, but was negatively correlated with E-cadherin expression in microarray specimens and in cell lines. FoxM1 overexpression was correlated significantly with HCC metastasis and EMT. In vitro, we found that FoxM1 plays a key role in HGF-induced EMT, and overexpression of FoxM1 could suppress E-cadherin expression and induce EMT changes, which were associated with increased HCC cell invasiveness. Next, we confirmed that FOXM1 directly binds to and activates the SNAI1 promoter, and we identified SNAI1 as a direct transcriptional target of FOXM1. Moreover, inhibiting the expression of SNAI1 significantly inhibited FoxM1-mediated EMT. CONCLUSION: FoxM1 overexpression promotes EMT and metastasis of HCC, and SNAI1 plays a critical role in FoxM1-mediated EMT.

Overexpression of PSF1 is correlated with poor prognosis in hepatocellular carcinoma patients.

BACKGROUND: PSF1 is a subunit of the GINS complex which is essential for establishment of DNA replication forks, and the progression of the replisome. Previous studies have shown a close relationship between PSF1 and cell cycle in the proliferation of immature cells as well as tumors. The purpose of this study was to measure PSF1 expression in hepatocellular carcinoma (HCC) tissues, and determine the effects of down-regulation of PSF1 expression on growth of cancer cells, the cell cycle, apoptosis and cell invasiveness. METHODS: Samples from 137 HCC tissues, 67 from adjacent nontumor tissue and 15 from normal liver were studied using immunochemistry. The HepG2 cell line was used for knockdown experiments studied by RT-PCR, real-time PCR, apoptosis and invasiveness assays. RESULTS: PSF1 was overexpressed in HCC tissues compared with normal liver tissues. High PSF1 expression correlated with a more aggressive phenotype as well as worse prognosis in HCC patients. Knockdown of PSF1 expression using small interfering RNA (siRNA) slowed the growth of cancer cell by suppressing the cell cycle progression as well as increasing apoptosis, especially early apoptosis. In addition, the invasiveness of HepG2 cells was also reduced by down-regulation of PSF1. CONCLUSIONS: These results suggest that the inhibition of PSF1 might provide new therapeutic approaches for HCC.

Down-regulation of FoxM1 inhibits viability and invasion of gallbladder carcinoma cells, partially dependent on inducement of cellular senescence.

AIM: To investigate the effect of knockdown of Forkhead box M1 (FoxM1) on the proliferation and invasion capacities of human gallbladder carcinoma (GBC)-SD cells. METHODS: Four FoxM1 shRNAs were transfected into GBC-SD cells with Lipofectamine 2000 to select the appropriate shRNA for down-regulation of FoxM1. A recombinant lentivirus for shFoxM1 (Lv-shFoxM1), which expresses FoxM1-specific shRNA, and a negative control carrying green fluorescent protein, which expresses a scrambled RNA, were constructed. After transfection with the recombinant adenovirus and screened with puromycin, RT-PCR and Western blot were utilized to evaluate the inhibition efficiency. Cell viability was evaluated by MTT assay, and cell migration and invasion were assessed using the Transwell system. Cells were suspended in serum-free medium and seeded into Transwell inserts either uncoated (for migration assay) or coated (for invasion assay) with growth factor-reduced Matrigel. To verify the involvement of FoxM1 in the senescence of tumor cells, staining of senescence ß-galactosidase (SA ß-gal), the widely used biomarker of cellular senescence, was also performed. RESULTS: After successful transfection of four FoxM1 small interfering RNAs (shRNAs) with Lipofectamine 2000, the shF1822 was selected as the most appropriate shRNA according to its obvious inhibitory effect. The recombinant adenovirus was then constructed with the shF1822 and successfully transfected into the GBC-SD cells, resulting in the significant inhibition of FoxM1 expression at both the mRNA and protein levels, compared with the negative control (P < 0.05). After transfection, down-regulation of FoxM1 significantly inhibited cell viability according to the MTT assay (P < 0.05). In addition, Transwell migration and invasion assays also suggested the suppression of invasion ability of the transfected cells. SA ß-gal staining showed that down-regulation of FoxM1 could induce more senescent GBC cells (P < 0.05), suggesting the possible involvement of the senescence process of the FoxM1-deficient cells in GBC. CONCLUSION: FoxM1 is functionally involved in viability of GBC cells, partially dependent on the inducement of cellular senescence, and is a potential target for GBC therapy.

Emodin induces human T cell apoptosis in vitro by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction.

AIM: To elucidate the molecular mechanisms underlying the immunosuppressive effects of emodin isolated from Rheum palmatum L. METHODS: Human T cells were isolated from the peripheral venous blood of 10 healthy adult donors. Cell viability was analyzed with MTT assay. AO/EB and Annexin V/PI staining and DNA damage assay were used to detect cell apoptosis. Fluorescence staining was used to detect the levels of ROS, the mitochondrial membrane potential and intracellular Ca(2+). Colorimetry was used to detect the levels of MDA and total SOD and GSH/GSSG ratio. The expression and activity of caspase-3, -4, and -9 were detected with Western blotting and a fluorometric assay. Western blotting was also used to detect the expression of Bcl-2, Bax, cytochrome C, and endoplasmic reticulum (ER) markers. RESULTS: Emodin (1, 10, and 100 µmol/L) inhibited the growth of human T cells and induced apoptosis in dose- and time dependent manners. Emodin triggered ER stress and significantly elevated intracellular free Ca(2+) in human T cells. It also disrupted mitochondrial membrane potential, and increased cytosolic level of cytochrome C, and the levels of activated cleavage fragments of caspase-3, -4, and -9 in human T cells. Furthermore, emodin significantly increased the levels of ROS and MDA, inhibited both SOD level and GSH/GSSG ratio in human T cells, whereas co-incubation with the ROS scavenger N-acetylcysteine (NAC, 20 µmol/L) almost completely blocked emodin-induced ER stress and mitochondrial dysfunction in human T cells, and decreased the caspase cascade-mediated apoptosis. CONCLUSION: Emodin exerts immunosuppressive actions at least partly by inducing apoptosis of human T cells, which is triggered by ROS-mediated ER stress and mitochondrial dysfunction.

Potential therapeutic targets for the primary gallbladder carcinoma: estrogen receptors.

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, ERα, ERß and ERγ. ERα and ERß appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

Gallbladder cancer: a subtype of biliary tract cancer which is a current challenge in China.

Biliary tract cancers, broadly described as malignancies that arise from the biliary tract epithelia, are usually divided into two major clinical phenotypes: cholangiocarcinoma and gallbladder cancer, differing in etiopathogenesis, risk factors, and perhaps molecular and genetic signatures. Atypical symptoms and lack of tumor biomarkers make it difficult to diagnose in early stages. At the time of presentation, few patients are candidates for potentially curative surgical resection. We here assessed and compared features of a total of 150 cases divided into extra- and intrahepatic cholangiocarcinomas and gallbladder cancers (GBC). Although there were no significant differences in serum tumour marker levels, GBC patients had the poorest prognosis. Furthermore, gallbladder cancer respond poorly to chemotherapy or radiation therapy and approximately half of untreated patients died within 10 months. Therefore, treatment for patients with gallbladder cancer is still in challenge. Outcomes and survival of these patients had improved little over the past three decades - a period in which new successful treatments have greatly contributed to the prolonged patient survival for many other cancers.

Pyogenic liver abscesses associated with nonmetastatic colorectal cancers: an increasing problem in Eastern Asia.

AIM: To elaborate the clinicopathologic features of colorectal cancer-related pyogenic liver abscess (PLA). METHODS: Reported cases of colorectal cancer-related PLAs were collected from the literature published up to October 2011 and evaluated for their clinicopathologic features. Data of collected cases included demographics, clinical presentation, microbial findings and treatment. Categorical variables were compared by χ² analysis and continuous variables were evaluated using Student's t test. RESULTS: A total 96 cases of colorectal cancer-related PLA were collected from the previous literature. Most patients (60%) were male and 40% cases occurred in the age group of 61-70 years. Apart from some special types of PLA, there were significant differences in the microbiological spectrum between Eastern Asia and non-Eastern Asian countries, which implied different risk factors and courses of the disease. Gram negative bacteria especially Klebsiella pneumoniae (K. pneumoniae) PLA was predominant in Eastern Asia (80.0%) in contrast to non-Eastern Asian countries (P < 0.01). Meanwhile, most of the Eastern Asian patients exhibited smaller size of liver abscess and atypical presentation. Sigmoid colon and rectum (72.73%) were the main sites of tumor in Eastern Asian patients, whereas tumor sites were uneven among most of the non-Easter Asian PLA patients. CONCLUSION: K. pneumoniae PLA was strongly associated with colorectal cancer, especially those occurring in sigmoid colon and rectum, in elderly Eastern Asian male patients.

A rare giant gastrointestinal stromal tumor of the stomach traversing the upper abdomen: a case report and literature review.

We present the case of a 66-year-old woman with a huge gastrointestinal stromal tumor of the stomach that traversed her upper abdomen. The predominant abdominal sign was a huge, palpable mass, but there were no other distinctive findings in her physical examination or her routine blood workup, including biochemical markers. It was difficult to judge the origin of the mass upon imaging. Furthermore, radiological findings revealed that the mass had a complex relationship with many major blood vessels. An exploratory laparotomy revealed a huge tumor protruding from the anterior wall of the stomach fundus, on the lesser curvature of the stomach, measuring approximately 21 × 34 × 11 cm in diameter and weighing 5.5 kg. A complete resection was performed and the tumor was characterized on immunohistochemistry as a gastrointestinal stromal tumor of the stomach. Preoperative diagnosis of gastrointestinal stromal tumors can be difficult, and we hope that the presentation of this rare case and literature review will benefit other diagnosing clinicians having similar problems.

Prognosis and management for gallbladder cancer with hepatic invasion: long-term results of 139 patients from a single center in China.

OBJECTIVE: To improve the diagnosis of primary gallbladder carcinoma (GBC) with/without hepatic metastases by analyzing our experience of different GBC treatment in our patients. METHODS: A retrospective study was carried out to analyze the clinical data of the 139 patients with GBC who underwent hepatic resection in our unit from January 2003 to December 2007. Patients were divided into two groups according to whether they demonstrated hepatic invasion. Tumor presentation, surgical modes, and prognosis of each patient were retrospectively reviewed. Kaplan-Meier curves and log-rank tests were employed to compare the survival rates of those patients undergoing different surgical procedures. RESULTS: Of the 139 patients, 46 were men and 93 were women with the male to female ratio of 1:2.0. Their ages were ranged from 35 to 86 years with a mean age of 62.8±10.4 years. There were 73 patients complicated with hepatic invasion (group A), and no hepatic invasion occurred in the other 66 patients (group B). Compared with the group B, the patients with hepatic invasion suffered lower differentiation of tumor (p=0.000), more advanced Nevin staging (p=0.008) and poorer prognosis (p=0.013). Radical resection were more frequently performed in group B (75.76%) than in group A (45.20%) with better outcomes (p=0.000). CONCLUSION: GBC patients complicated with hepatic invasion had poorer prognosis than those without invasion in long-term follow-ups. Radical resection might result in a satisfied prognosis in patients without hepatic invasion, but appears less favorable than palliative resection in those who were complicated with hepatic invasion.

Long-term prognosis in hepatocellular carcinoma patients after hepatectomy.

BACKGROUND: The hepatocellular carcinoma is very common in China. Our aim in this report was to investigate clinical and pathological factors based on the current decade data that could influence prognosis of HCC patients after hepatectomy. METHODS: Between 2002 and 2009, all patients undergoing hepatectomy for HCC were followed up and reviewed retrospectively. Prognostic factors were studied by univariate and multivariate analysis, with Kaplan-Meier and Cox multivariate survival analyses. RESULTS: Complete clinicopathologic and follow-up data were available for 114 patients. The estimated cumulative survival rates at 1, 3, and 5 yr were 84.6%, 60.2% and 51.8%, respectively. On univariate analysis, key prognostic factors were AFP level, GGT level, tumor size, number of tumors, portal vein invasion, liver cirrhosis status and TNM stage. In the multivariate analysis, tumor size, GGT level, liver cirrhosis status and portal vein invasion were significantly associated with patients' prognosis. CONCLUSION: Through follow-up of a relatively large cohort of Chinese patients, tumor size, GGT level, liver cirrhosis status, portal vein invasion were revealed as important factors for long-term survival after hepatectomy. Early diagnosis for tumor and the improvement of liver function before surgery are important ways to improve the prognosis.

Distinctions between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive hepatocelluar carcinoma patients.

Serum alpha-fetoprotein (AFP) is a significant marker for clinical diagnosis and prognosis evaluation in hepatocellular carcinoma (HCC) patients. However, some proportion of liver cancer patients are AFP-negative (AFP ≤20 ng/ml). In order to study the differences between clinicopathological factors and prognosis of alpha-fetoprotein negative and positive patients, a total of 114 cases (41 AFP-negative and 73 AFP-positive) were selected for our research. By systematically statistical analysis, the results demonstrated that compared with AFP-negative patients, AFP-positive examples were more likely to feature cirrhosis nodules, non-complete neoplasm capsules, and a poor Edmondson-steiner grade. Furthermore, AFP-negative patients demonstrated a favorable long-term prognosis. By univariate analysis and multivariate analysis with Cox's proportional hazards model, multiple tumors were found to be independent risk factors for worse survival of AFP negative patients; however, less tumor-free margins, multiple tumors and Edmondson-steiner grades III/IV, proved to be independent risk factors leading to a poor prognosis of AFP positive cases. Finally, we can infer that high levels of AFP signify a highly malignant tumor and unfavorable prognosis.