OBJECTIVES: Hepatocellular carcinoma is one of the most common primary malignant tumors with the third highest mortality rate worldwide. This study aims to identify key genes associated with hepatocellular carcinoma prognosis using the Gene Expression Omnibus (GEO) database and provide a theoretical basis for discovering novel prognostic biomarkers for hepatocellular carcinoma. METHODS: Hepatocellular carcinoma-related datasets were retrieved from the GEO database. Differentially expressed genes (DEGs) were identified using the GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and key genes were identified using Cytoscape software. The University of Alabama at Birmingham Cancer Data Analysis Resource (UALCAN) was used to analyze the expression levels of key genes in normal and hepatocellular carcinoma tissues, as well as their associations with pathological grade, clinical stage, and patient survival. The Human Protein Atlas (THPA) was used to further validate the impact of key genes on overall survival. Expression levels of key genes in the blood of hepatocellular carcinoma patients were evaluated using the expression atlas of blood-based biomarkers in the early diagnosis of cancers (BBCancer). RESULTS: A total of 78 DEGs were identified from the GEO database. GO and KEGG analyses indicated that these genes may contribute to hepatocellular carcinoma progression by promoting cell division and regulating protein kinase activity. Sixteen key genes were screened via Cytoscape and validated using UALCAN and THPA. These genes were overexpressed in hepatocellular carcinoma tissues and were associated with disease progression and poor prognosis. Finally, BBCancer analysis showed that ASPM and NCAPG were also elevated in the blood of hepatocellular carcinoma patients. CONCLUSIONS This study identified 16 key genes as potential prognostic biomarkers for hepatocellular carcinoma, among which ASPM and NCAPG may serve as promising blood-based markers for hepatocellular carcinoma.
Humans ; Carcinoma, Hepatocellular/mortality* ; Liver Neoplasms/pathology* ; Prognosis ; Computational Biology/methods* ; Protein Interaction Maps/genetics* ; Biomarkers, Tumor/genetics* ; Gene Expression Regulation, Neoplastic ; Gene Expression Profiling ; Gene Ontology ; Databases, Genetic

BACKGROUND: The purpose of this study is to compare the survival time of non-small cell lung cancer (NSCLC) patients with different organ metastasis. Among all cancers, the morbidity and mortality of lung cancer is the highest worldwide, which may caused by local recurrence and distant metastasis, and the location of metastasis may predict the prognosis of patients. METHODS: A total of 117,542 patients with NSCLC diagnosed between 2010 and 2014 were enrolled from Surveillance, Epidemiology, and End Result (SEER) databases, and the relationship between distant metastasis and survival time was retrospectively analyzed. RESULTS: Of all the 117,542 patients diagnosed with non-small cell lung cancer, 42,071 (35.8%) patients had different degrees of distant metastasis during their medical history, including 26,932 single organ metastases and 15,139 multiple organ metastases, accounting for 64.0% and 36.0% of the metastatic patients respectively. Compared with patients with no metastasis, whose median survival time was 21 months, the median survival time of patients with metastases was 7 months (lung), 6 months (brain), 5 months (bone), 4 months (liver), and 3 months (multiple organ) respectively, and the difference was significant (P<0.001, except liver vs multiple organ P=0.650); Most patients with NSCLC (88.4%) eventually died of lung cancer. CONCLUSIONS Distant metastasis of NSCLC patients indicates poor prognosis. In NSCLC patients with single organ metastasis, the prognosis of lung metastasis is the best, and liver metastasis is the worst, and multiple organ metastasis is worse than single organ metastasis.
Aged ; Aged, 80 and over ; Bone Neoplasms ; mortality ; secondary ; Brain Neoplasms ; mortality ; secondary ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; Female ; Humans ; Liver Neoplasms ; mortality ; secondary ; Lung Neoplasms ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies

BACKGROUNDHuman U three protein 14a (hUTP14a) promotes p53 degradation. Moreover, hUTP14a expression is upregulated in several types of tumors. However, the expression pattern of hUTP14a in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate hUTP14a expression and its prognostic value in HCC.

METHODSThe hUTP14a expression was evaluated using immunohistochemistry (IHC) in HCC tissue specimens. The correlations between hUTP14a expression and clinicopathological variables were analyzed. The Kaplan-Meier method was used to analyze the association between hUTP14a expression and survival. Independent prognostic factors associated with overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox proportional-hazards regression model.

RESULTSThe IHC data revealed that the hUTP14a positivity rate in HCC tissue specimens was significantly higher than that in nontumorous tissue specimens (89.9% vs. 72.7%, P < 0.05). The hUTP14a expression was detected in both the nucleolus and the cytoplasm. The positivity rate of nucleolar hUTP14a expression in HCC tissue specimens was higher than that in the nontumorous tissue specimens (29.3% vs. 10.1%, P < 0.05). No significant difference was found between HCC and nontumorous tissue specimens of cytoplasmic hUTP14a expression (60.6% vs. 62.6%, P > 0.05). In addition, no significant correlation was found between nucleolar hUTP14a expression and other clinicopathological variables. The 5-year OS and DFS rates in patients with positive nucleolar hUTP14a expression were significantly lower than those in patients with negative hUTP14a expression (P = 0.004 for OS, P = 0.003 for DFS). Multivariate analysis showed that nucleolar hUTP14a expression was an independent prognostic factor for OS (P = 0.004) and DFS (P < 0.001).

CONCLUSIONSThe positivity rate of hUTP14a expression was significantly higher in HCC specimens. Positive expression of nucleolar hUTP14a might act as a novel prognostic predictor for patients with HCC.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Ribonucleoproteins, Small Nucleolar ; genetics ; metabolism

BACKGROUND/AIMS: We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone. METHODS: This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC < or = 5.0 cm or up to three HCCs < or = 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43). RESULTS: The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively). CONCLUSIONS: TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; *Catheter Ablation/adverse effects/mortality ; *Chemoembolization, Therapeutic/adverse effects/mortality ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/mortality/pathology/*therapy ; Male ; Middle Aged ; *Neoadjuvant Therapy/adverse effects/mortality ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Patient Selection ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; Young Adult

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Carcinoma, Hepatocellular/blood/mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/blood/mortality/*pathology/therapy ; *Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. METHODS: In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. RESULTS: During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. CONCLUSIONS: Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.
Aged ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Catheter Ablation ; Female ; Hepatitis B/complications ; Hepatitis C/complications ; Humans ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome

BACKGROUND/AIMS: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. METHODS: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. RESULTS: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1-B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo' (2-4) nodules of intermediate size (5-10 cm) when the AFP levels was <400 ng/ml, or ‘oligo' (2-4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). CONCLUSIONS: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.
Adult ; Aged ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Chemoembolization, Therapeutic ; Female ; Hepatectomy ; Humans ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate ; Treatment Outcome ; alpha-Fetoproteins/analysis

OBJECTIVEThe aim of this study was to analyze the clinical features and prognostic factors in patients with brain metastasis from colorectal cancer (CRC).

METHODSClinical materials of 45 colorectal cancer patients who developed brain metastasis were collected, and the data and follow-up data of those patients were retrospectively analyzed.

RESULTSMost brain metastases were from rectal cancer (64.4%), and 80.0% of the 45 cases had extracranial metastases. The most common extracranial metastatic site was the lung (57.8%), followed by the liver (35.6%). All the brain metastases in patients with liver metastases were supratentorial, while in contrast, 44.8% of the patients without liver metastasis had subtentorial metastasis, showing a significant difference between them (P<0.05). The interval time from diagnosis of CRC to the development of brain metastases in case of Dukes D stage was 12.0 months, significantly shorter than that in the cases of Dukes A stage (24.0 months), B (36.0 months) and C (29.0 months) (P<0.05). The interval time was also shorter in the patients who developed extracranial metastasis within one year than those more than one year (12.0 months vs. 38.0 months)( P<0.05). The median survival time of patients with brain metastasis from colorectal was 6.0 months, with a 1-year survival rate of 21.1% and 2-year survival rate of 3.3% only. Univariate analysis showed that the median survival of patients with a KPS score of ≥70 was 8.0 months, significantly higher than 2.0 months in those with a KPS score of <70 (P<0.05). The median survival of patients with one or two brain metastases was 8.0 months, significantly higher than 4.0 months of those with >2 brain metastases (P<0.05). The median survival time after diagnosis of brain metastasis was 4.0 months for those who received monotherapy (only steroids, only chemotherapy or only radiotherapy), significantly shorter than 10.0 months of patients who received chemoradiotherapy, and 12.0 months of those who underwent surgery (P<0.05). Comparing each two differently treated groups, the survival time of surgery combined with chemotherapy or radiotherapy group was significantly different from that of all of other groups (P<0.05). The median survival time of chemoradiotherapy group was longer than that of monotherapy, but the difference was not significant (P>0.05). Multivariate analysis showed that brain metastases >2 and treatment modality type are independent prognostic factors for survival.

CONCLUSIONSPatients initially diagnosed with a Dukes D stage primary colorectal tumor and occurrence of extracranial metastasis (especially, pulmonary metastasis) within one year are associated to an increased risk of brain metastases and have a shorter survival time. Most brain metastases in patients with liver metastases are supratentorial, while many patients without liver metastasis have subtentorial metastasis. Brain metastases >2 and the type of treatment modality are independent prognostic factors for survival. The prognosis of patients who received chemoradiotherapy is better than those treated only with chemotherapy or radiotherapy. Some subsets of patients may benefit from surgery plus chemotherapy/radiotherapy.

Brain Neoplasms ; mortality ; secondary ; therapy ; Chemoradiotherapy ; Colorectal Neoplasms ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; pathology ; Retrospective Studies ; Survival Rate ; Time Factors

OBJECTIVETo explore the significance of resection margin and tumor number on survival of patients with small liver cancer after hepatectomy.

METHODSWe collected 219 cases with small liver cancer undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 to July 2013. The survival rates were compared by log-rank test between two resection margin groups (≥ 1 cm vs. <1 cm), different tumor number groups (single tumor vs. multiple tumors). We also performed a multifactor analysis by Cox model.

RESULTSThe 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3%, respectively, in all patients. The median survival time was 28 months in the group of <1 cm resection margin and 36 months in the group of ≥ 1 cm resection margin (P=0.249). The median survival time was 36 months in the group of single tumor and 26 months in the group of multiple tumors (P=0.448). The multifactor analysis also did not show significant effect of resection margin and tumor number on the patients' survival.

CONCLUSIONSFor small liver cancer, the resection margin of 1 cm might be advised. Increasing resection margin in further could probably not improve therapeutic effect. Standardized operation and combined treatment will decrease the negative influence of multiple tumors on overall survival.

Combined Modality Therapy ; Hepatectomy ; Humans ; Liver Neoplasms ; mortality ; pathology ; surgery ; Survival Rate ; Time Factors

BACKGROUNDHepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients.

METHODSThis study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic.

RESULTSThe overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7 th (TNM 7 th ) (AIC = 2899.980), TNM 6 th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389).

CONCLUSIONSBCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; mortality ; pathology ; China ; Female ; Humans ; Liver Neoplasms ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Survival Rate