Loss of heterozygosity at D8S298 is a predictor for long-term survival of patients with tumor-node-metastasis stage I of hepatocellular carcinoma.

PURPOSE: Our previous studies have shown that chromosome 8p deletion correlates with metastasis of hepatocellular carcinoma (HCC). This study was to determine whether 8p deletion could be used in predicting the prognosis of patients with HCC, particularly in those with early stage of HCC. EXPERIMENTAL DESIGN: A total of 131 patients with tumor-node-metastasis (TNM) stage I of HCC who underwent curative liver resection were enrolled. Loss of heterozygosity (LOH) was examined using 10 microsatellite markers at chromosome 8p, as well as 14 microsatellites at chromosome 1p, 17p, 4q, 13q, and 16q, and their association with 5-year overall survival (OS) and disease-free survival (DFS) of patients was analyzed. RESULTS: In the entire cohort of patients, the mean LOH frequency at these 24 loci was 43.2%; LOH frequencies at D8S298 and D1S199 were 31.5% and 33.7%, respectively. LOH at D8S298 was associated with a worse 5-year OS (P = 0.008) and DFS (P = 0.038) in patients with TNM stage I of HCC. Likewise, the patients with LOH at D1S199 had a worse 5-year OS (P < 0.001) and DFS (P = 0.014) compared with those without LOH at D1S199. In multivariate analyses, LOH at D8S298 was an independent predictor of decreased DFS (hazard ratio, 0.372; 95% 95% confidence interval, 0.146-0.948; P = 0.038), whereas LOH at D1S199 was an independent predictor of decreased OS (hazard ratio, 0.281; 95% confidence interval, 0.123-0.643; P = 0.003). CONCLUSIONS: LOH at D8S298 and D1S199 is independently associated with a worse survival in patients with TNM stage I of HCC after curative resection and could serve as novel prognostic predictors for this subgroup of patients.     

灵芝孢子对原发性肝癌术后复发影响的研究

目的探究灵芝孢子预防原发性肝癌根治术后复发的作用。方法采用完全随机对照的前瞻性临床研究,60例行根治切除的原发性肝癌患者随机分为术后常规治疗组和灵芝孢子治疗组,随访2年,观察术后无瘤生存率(DFS)、总体生存率(OS)和灵芝孢子的安全性。结果两组患者年龄、性别构成比、肿瘤大小以及术前AFP>20ng/ml、微血管侵犯、肿瘤卫星结节、乙肝感染、肝硬化患者比例的差异无统计学意义;术后抗病毒治疗患者比例以及术中输血、住院时间比较,差异无统计学意义(P<0.05)。术后常规治疗组和灵芝孢子治疗组的2年无瘤生存率分别为53.3%和70.0%(P=0.034),2年总生存率分别为60.0%和83.3%(P=0.023),差异有统计学意义。术后两组患者的并发症和药物副反应发生率无显著性差异(P=0.371)。结论灵芝孢子可以减少肝癌根治术后复发,安全有效。     

280例非小细胞肺癌患者围手术期输血与否的预后关系

目的：研究非小细胞肺癌术后的预后因素及围手术期输血对术后无病生存的影响。方法：回顾性调查了280例手术切除的非小细胞肺癌患者，其中145例（51．8％）患者围手术期接受了输血治疗，采用单因素对数秩检验（log—ranktest）多因素Cox比例风险回归模型进行分析。结果：多因素分析表明，影响预后的主要因素有分化程度、术后分期、围手术期输血。围手术期输血是无病生存的独立预后因素。结论：围手术期输血是非小细胞肺癌独立的不利预后因素，应当尽量避免围手术期输血。     

肿瘤负荷评分在肝细胞癌患者预后预测中的价值

目的 探讨肿瘤负荷评分（tumor burden score,TBS）预测肝细胞癌患者预后的价值。方法 回顾性收集487例行肝切除术肝细胞癌患者的临床资料。采用时间依赖的ROC曲线及曲线下面积（area under the ROC curve,AUC）评价TBS预测总生存率和无瘤生存率的准确性。多因素Cox回归筛选影响肝细胞癌患者预后的独立因素。结果 ROC曲线分析显示,TBS预测肝细胞癌患者术后5年生存率的AUC为0.722,高于肿瘤最大直径的AUC （0.711）和肿瘤数目的AUC（0.548）。TBS可将患者分成4个不同预后风险组,即TBS≤3组（n=70,14.4%）、3n=175,35.9%）、5n=150,30.8%）、TBS>8组（n=92,18.9%）,各组患者5年总生存率依次为87.5%、75.7%、62.9%和36.3%;5年无瘤生存率依次为62.4%、44.2%、31.1%和12.9%。组间总生存率和无瘤生存率比较差异均有统计学意义（P<0.001）。Cox多因素分析显示,TBS是影响肝细胞癌患者术后总生存率和无瘤生存率的独立因素。结论 TBS可较好地预测肝细胞癌患者肝切除术后的预后情况。     

Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort.

PURPOSE: This study aims to clarify the clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The clinicopathologic features of 5-year survivors and disease-free survivors were elucidated in a cohort of 230 patients prospectively observed for > 5 years (64 to 192 months) after curative resection of HCC. RESULTS: The incidence of 5-year overall and disease-free survivors were 37% (85 of 230) and 20% (45 of 230), respectively. Clinicopathologic features associated with 5-year survivors included female sex (P =.024), preoperative serum albumin > or= 40 g/L (P =.033), AST < 50 u/L (P =.001), tumor < 5 cm (P =.001), solitary tumor (P =.035), encapsulated tumor (P =.021), no venous invasion (P =.001), no microsatellite nodule (P =.001), and early pathologic tumor-node-metastasis (pTNM) stage (I or II, P <.001). Features favoring 5-year disease-free survivors were preoperative serum AST < 50 u/L (P =.007), tumor < 5 cm (P =.005), encapsulated tumor (P =.007), no venous invasion (P <.001), no microsatellite nodule (P =.001), and early pTNM stage (I or II, P <.001). By multivariate analysis, pTNM stage was the only significant predictive factor for both overall and disease-free survival. CONCLUSION: This study shows that long-term disease-free survival > 5 years after resection of HCC can be achieved in patients with favorable tumor characteristics. Early pTNM stage was the most reliable predictor of both long-term overall and disease-free survivors.     

Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741.

BACKGROUND: Fluorouracil (5-FU), oxaliplatin and irinotecan combinations improve time to tumor progression (TTP), objective response and overall survival (OS) in patients with metastatic colorectal cancer (MCRC). Here we identify and describe patients treated on Intergroup study N9741 who initially had inoperable MCRC, but who obtained sufficient chemotherapeutic benefit to allow removal of their metastatic disease. PATIENTS AND METHODS: Patient research records in study arms (A) irinotecan/5-FU/leucovorin (LV) (IFL, n = 264), (F) oxaliplatin/5-FU/LV (FOLFOX4, n = 267) and (G) oxaliplatin/irinotecan (IROX, n = 265) were reviewed. TTP and median OS were calculated. RESULTS: Twenty-four (3.3%) of 795 randomized patients underwent curative metastatic disease resection [hepatectomy, 16; radiofrequency-ablation (RFA), six; lung resection, two]. Twenty-two out of 24 (92%) resected patients received an oxaliplatin-based regimen (FOLFOX4, 11; IROX, 11). Seven patients (29.2%) remain disease-free; relapses occurred mainly in the resected organ. Median OS in resected patients is 42.4 months, and median TTP is 18.4 months. All six patients treated with RFA have recurred. Four out of five (80%) patients who received chemotherapy following resection are disease-free. CONCLUSIONS: Resection of metastatic disease after chemotherapy is possible in a small but important subset of patients with MCRC, particularly after receiving an oxaliplatin-based chemotherapy regimen, with encouraging OS and TTP observed in these highly selected patients.     

Long-term outcomes of 307 patients after complete thymoma resection

Background: Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection. Methods: We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses. Results: During follow-up (median, 86 months; range, 24–160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resec-tion had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017). Conclusions: Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.     

High KIF18A expression correlates with unfavorable prognosis in primary hepatocellular carcinoma

This study aimed to investigate KIF18A expression in hepatocellular carcinoma (HCC) and to determine the possibility of KIF18A expression being a biomarker in HCC diagnosis or being an independent predictor of disease-free survival (DFS) and overall survival (OS) in HCC patients underwent surgical resection. KIF18AmRNA was detected in 216 cases of HCC tissues by quantitative real-time PCR (qRT-PCR) and in 20 cases of HCC tissues by semi-quantitative RT-PCR. KIF18A protein was determined in 32 cases of HCC tissues by immunohistochemistry (IHC). The survival probability was analyzed by Kaplan-Meier method, and survival curves between groups were obtained by using the log-rank test. Independent predictors associated with DFS were analyzed with Stepwise Cox proportional hazard models. High KIF18A mRNA level was detected in 154 out of 216 (71.3%) cases of HCC. The positive rate of KIF18A expression was significantly higher in liver cancer tissues than that in adjacent normal liver tissues (ANLT) from HCC patients [65.6% (21 of 32) vs. 25.0% (8 of 32), P=0.001]. The KIF18A expression level had positive relevance to the alpha-fetoprotein (AFP) (≥200 ng/ml), tumor size (≥5cm), clinical tumor-node-metastasis (TNM) stage and portal vein tumor thrombus (PVTT) in HCC (all P <0.05). A survival analysis indicated that HCC patients with higher KIF18A expression had a significantly shorter DFS and OS after resection. A multivariate analysis suggested that KIF18A upregualtion was an independent factor for DFS [hazard risk (HR)=1.602; 95% confidence interval (CI), 1.029-2.579; P=0.031] and OS (HR=1.682; 95% CI, 1.089-2.600; P=0.019). KIF18A might be a biomarker for HCC diagnosis and an independent predictor of DFS and OS after surgical resection.     

Expression and prognostic significance of osteopontin and caspase‐3 in hepatocellular carcinoma patients after curative resection

Osteopontin (OPN) plays an important role in the development, invasion, and metastasis of malignancies. Recently, several studies have reported that OPN enhances chemoresistance in small‐cell lung cancer and breast cancer by blocking caspase‐9 and caspase‐3‐dependent cell apoptosis. The aim of this study was to assess the value of OPN and caspase‐3 for predicting tumor recurrence after curative resection in hepatocellular carcinoma (HCC) patients. We found that OPN expression increased concordantly with increasing metastatic potential in human HCC cell lines, whereas caspase‐3 expression declined. In a tumor tissue microarray immunohistochemical analysis, we found that patients with higher levels of OPN and lower levels of caspase‐3 had a significantly poorer prognosis than patients with lower OPN and higher caspase‐3 levels. The combination of OPN and caspase‐3 expression thus served as an effective prognosticator. These findings suggest that OPN alone or in combination with caspase‐3 may act as an independent indicator for HCC patients after curative resection. (Cancer Sci 2010; 101: 1314–1319)     

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

Clinicopathologic features and postoperative outcomes were investigated for patients who underwent curative surgery for biliary marker (CK7 and CK19)-positive hepatocellular carcinoma (HCC). Of 157 HCCs, 93 were CK7(-)CK19(+), 49 were CK7(+)-CK19(-), 1 was CK7(-)CK19(+), and 14 were CK7(+)-CK19(+). Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness.     

What patients can survive disease free after complete resection for hepatocellular carcinoma?: A multivariate analysis

BACKGROUND: Although there have been extensive studies to determine risk factors affecting survival after resection for hepatocellular carcinoma (HCC), we still do not know which patients can survive disease free after curative resection. This study was undertaken to determine independent risk factors affecting the length of disease-free survival. METHODS: 171 patients, who survived disease free more than 1 year after curative resection, were divided into four groups according to the disease-free period: Group I (n = 96) for the patients with intrahepatic recurrence between 1 and 3 postoperative years, Group II(n = 27) for those between 3 and 5 years, Group III (n = 40) for those between 5 and 10 years and Group IV (n = 8) for those without recurrence within 10 years. The 37 variables (host factors, tumor factors, non-tumor liver factors, surgical factors) were compared among the four groups. Activity of hepatitis and hepatic fibrosis was scored by the Histological Activity Index (HAI). In a multivariate study, possible prognostic variables with a statistical difference in the disease-free survival rate among each category were preliminarily selected from the 37 variables and the independent variables were finally selected using a proportional hazard analysis. RESULTS: The patients' age, indocyanine green retention rate, microscopic tumor capsular invasion and portal invasion, cell differentiation, extent of hepatectomy, aggressiveness of chronic hepatitis and inflammatory activity assessed by HAI score were significantly different among the four groups. In the multivariate analysis, the following variables were selected as the independent determinants favorable for achieving a longer disease-free period: younger age, lower indocyanine green retention rate, solitary HCC with expansive growth, no microscopic portal invasion and lower activity of co-existing hepatitis. CONCLUSIONS: The importance of inflammatory activity in addition to aging, hepatic reserve and tumor characteristics was confirmed as a risk factor for recurrence by multivariate analysis. To achieve better disease-free survival, not only early detection but also suppression of co-existing hepatitis is necessary.     

肝细胞癌切除术标准及其临床意义*

目的:阐述肝细胞癌（肝癌）切除术标准,为把握手术指征、指导治疗、提高疗效提供依据。方法:使用CNKI、NCBI生物信息学数据库,以“肝切除/liver resection 、肝癌/hepatocellular carcinoma（HCC ）”为关键词,检索已发表的文章,排除重复研究和与本研究无关文献后精选纳入分析。总结肝切除标准分类,陈述其关键因素和争议焦点,比较不同标准肝切除患者预后,讨论预后差异的可能原因。结果:HCC 切除术标准的主流分法为二分法,即根治性和姑息性切除,其关键因素包括外科、肿瘤及随访因素,肝切缘大小是否影响根治效果曾是外科因素中争论热点。近年,随着肿瘤分子生物学技术的进步,学者们对HCC 切除术标准的分法有所改变,在三分法（病理根治、临床根治和姑息切除）基础上提出HCC 切除术五分法,将病理根治划分为绝对根治（无潜在转移）和相对根治（有潜在转移）,临床根治划分为有反应切除（短期内相关指标下降,如甲胎蛋白）、无反应切除（指标持续异常）和姑息性切除。根治性切除患者预后好于姑息性切除。研究显示,肝切除促进肿瘤侵袭转移潜能可能与HCC 早期播散有关,也可能与术后残余HCC 生物学特性改变相关,目前缺乏有效的干预措施。结论:根治性肝切除是目前公认的治疗HCC 患者最有效的方法之一;确定HCC 切除术标准有利于总结、分析临床资料,也有利于评估患者预后,对选择有效的治疗策略具有重要的临床意义。      

C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases

There is increasing evidence that systemic inflammatory response has a positive correlation with a poorer outcome in patients undergoing resection for solid tumours. The aim of this study was to analyse the impact of an elevated C-reactive protein (CRP), an outcome following curative resection for colorectal liver metastases. One hundred and seventy patients who underwent curative resection for colorectal liver metastases were included in the study. Laboratory measurements of haemoglobin, white cell, platelets, albumin and CRP were taken on the day before surgery. Elevated CRP (>10 mg l(-1)) was present in 54 (31.8%) patients. The median survival of patients with an elevated CRP was 19 months (95% CI 7.5-31.2 months) compared to 42.8 months (95% CI 33.2-52.5 months) for those with a normal CRP, P=0.004. Similarly, when assessing disease-free survival, patients with an elevated CRP had poorer disease-free survival (median of 11.8 months (95% CI 6.4-17.3) compared to median of 15.1 months (95% CI 11.1-19.1)), P=0.043. The result of the study showed that an elevated preoperative CRP is a predictor of poor outcome in patients undergoing curative resection for colorectal liver metastases.     

Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor

BACKGROUND: Few studies have investigated the pathologic types and prognosis of hepatocellular carcinoma (HCC) with lymph node metastasis (LNM). The purpose was to explore pathologic types and pertinent therapy of HCC with LNM. METHODS: An immunohistochemical study for CK19 and OV-6 was performed on tissue microarrays of HCC with LNM (n=47) and those without LNM (n=125). The clinicopathologic factors and patient survival were analyzed. RESULTS: Immunopositivity of CK19 and OV-6 in HCC with LNM were higher than that in 125 HCC without LNM (27.7% vs 5.6%, P=.000; 29.8% vs 12.8%, P=.009); their expressions were significantly correlated in HCC with LNM (correlation coefficient: 0.637, P=.000). The CK19 expression and tumor (T) classification of American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) tumor staging system were 2 independent risk factors for developing LNM (odds ratio [OR], 5.170, 95% confidence interval [CI], 1.840-14.528, P=.002; OR, 1.879, 95% CI, 1.236-2.857, P=.003). The CK19(+) group had shorter median survival (7.7 months vs 21.7 months, P=.013); CK19 expression was the independent prognostic factor for overall survival in HCC with LNM and was correlated with proliferating cell nuclear antigen labeling index and matrix metalloproteinase-9 expression (correlation coefficient: 0.484, P=.001 and 0.459, P=.001, respectively). CONCLUSIONS: CK19 expression and AJCC/UICC T classification were 2 independent risk factors for developing LNM in HCC. CK19 expression was the independent prognostic factor for HCC with LNM. It is of clinical significance for treatment modalities to differentiate HCC with intrahepatic cholangiocarcinoma-like differentiation (CK19[+]) from one with a higher T classification (CK19[-]).     

Surgical results for hepatocellular carcinoma with bile duct invasion: a clinicopathologic comparison between macroscopic and microscopic tumor thrombus

BACKGROUND: The aim of this study was to evaluate the prognostic factors and long-term results after surgery in patients with hepatocellular carcinoma (HCC) with bile duct invasion. METHODS: The records of 38 HCC patients with microscopic (tumor thrombus was found in more than the second order branch of the biliary tree; n = 19) and macroscopic (tumor thrombus was found in no more than the second order branch of the biliary tree; n = 19) bile duct invasion were reviewed in this study. Survival rates were calculated with regard to 18 clinicopathological factors. A log-rank analysis was performed to identify which factors predict the prognosis. The relationships between the degree of bile duct invasion and 17 clinicopathologic factors were also compared. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79%, 45%, and 33%, respectively. The indicators of a favorable prognosis included no intrahepatic metastases, curative surgical resection, and macroscopic bile duct invasion. CONCLUSION: We found a favorable long-term postoperative result for HCC patients with macroscopic bile duct invasion. Even if HCC tumor thrombus is recognized in the major branches of bile duct, extensive and curative surgical treatment should be recommended when hepatic functional reserve is satisfactory without intrahepatic metastases.     

Pulmonary resection for metastatic colorectal cancer

We reviewed the clinical courses of 25 patients who underwent pulmonary resection for metastatic lesions from colorectal cancer between January 1991 and December 2001. The cumulative survivals at 3 and 5 years were 72% and 63%, respectively. Sex, site of the primary tumor, presence of extrapulmonary metastases, disease-free interval, location of pulmonary metastases (PM), number of PM, size of PM, mode of operation, pre-thoracotomy serum carcinoembryonic antigen level, and post-thoracotomy chemotherapy were not found to be statistically significant prognostic factors. Age (70 years < or =) was a predictor of a shorter survival duration by univariate analysis (p = 0.02). Recurrence was observed in 19 patients, 11 of which were lung recurrences. Eight patients underwent repeated pulmonary resection. The median survival in these 8 patients was 23 months after second pulmonary operation. Surgical treatment for pulmonary metastases from colorectal cancer in selected patients might improve prognosis.     

Surgical microwave ablation for multifocal non-resectable liver metastases: a single institution experience treating five or more liver lesions

BackgroundThermal ablation is an effective treatment for patients with metastatic colon and rectal cancer and allows surgeons to offer curative intent therapy to patients who are otherwise not candidates for resection. We aimed to report outcomes of a single institution experience using microwave ablation (MWA) with or without resection to treat five or more liver metastases.MethodsIn this retrospective cohort study, the University of Minnesota Division of Surgical Oncology liver surgery database was queried to identify all patients who underwent thermal ablation of five or more colorectal liver metastases (CRLM) between 2012–2018. We reviewed patient, disease, and tumor characteristics and measured local, intrahepatic, and extrahepatic recurrence (EHR) rates. We also calculated median overall survival (OS) and disease-free survival (DFS).ResultsTen patients identified had five or more (range, 5–18) tumors ablated with or without combined liver and bowel resection. Median age was 50, and most patients were male (70%) and Caucasian (90%). Four patients received ablation alone (5–12 lesions), while six had combined resection and ablation (5–18 lesions). Ablation was performed laparoscopically in six patients, and four had ablations without resection. All patients received pre- and post-operative chemotherapy. A median of 7 tumors were ablated per patient. Median follow-up was 2.3 years. Among 75 tumors ablated, ablation site recurrence (ASR) (within 1 cm of ablation site) was seen in three with a per-lesion recurrence rate of 4%. Intrahepatic recurrence (IHR) occurred in 6 (60%) patients and EHR in 1 (10%). Five patients underwent retreatment of IHR during follow-up. Median OS was 3 years and DFS was 7.1 months. At the time of last follow up, 6 patients were disease-free.ConclusionsThermal ablation can provide acceptable DFS and OS, even with high volume metastatic colorectal cancers. Future efforts should be focused on defining selection criteria for those most likely to benefit from this aggressive approach.     

Epidermal growth factor receptor pathway polymorphisms and the prognosis of hepatocellular carcinoma

The EGFR signaling pathway is important in the control of vital processes in the carcinogenesis of hepatocellular carcinoma (HCC), including cell survival, cell cycle progression, tumor invasion and angiogenesis. In the current study, we aim to assess if genetic variants in the genes of the EGFR signaling pathway are associated with the prognosis of HCC. We genotyped 36 single nucleotide polymorphisms (SNP) in four core genes (EGF, EGFR, VEGF, and VEGFR2) by using DNA from blood samples of 363 HCC patients with surgical resection. The associations between genotypes and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confident intervals (CIs) were estimated for the multivariate survival analyses by Cox proportional hazards regression models, adjusting for age, gender, family history, HBsAg and AFP. We found that five SNPs in the VEGFR2 gene were significantly associated with clinical outcomes of HCC patients. Among them, four SNPs (rs7692791, rs2305948, rs13109660, rs6838752) were associated with OS (p=0.035, 0.038, 0.029 and 0.028, respectively), and two SNPs (rs7692791 and rs2034965) were associated with DFS (p=0.039 and 0.017, respectively). Particularly, rs7692791 TT genotype was associated with both reduced OS (p=0.037) and DFS (p=0.043). However, only one SNP rs2034965 with the AA genotype was shown to be an independent effect on DFS (p=0.009) in the multivariate analysis. None of the other 31 polymorphisms or 9 haplotypes attained from the four genes was significantly associated with OS or DFS. Our results illustrated the potential use of VEGFR2 polymorphisms as prognostic markers for HCC patients.     

Prognostic significance of osteopontin in hepatocellular carcinoma: a meta-analysis

Osteopontin (OPN) has been implicated in tumor development and progression for several years. However, the prognostic value of OPN overexpression in patients with hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to assess the relationship between OPN overexpression and clinical outcome of HCC. A meta-analysis of seven studies (1,158 patients) was carried out to evaluate the association between OPN and overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between OPN and tumor vascular invasion or other invasion-related parameters was also assessed. Data were synthesized with random effect model of DerSimonian and Laird, hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that high OPN expression predicted poor OS (HR: 1.37, 95% CI: 1.21-1.55) and DFS (HR: 1.62, 95% CI: 1.24-2.11) of HCC. OPN overexpression tended to be associated with the presence of tumor vascular invasion (OR: 1.93, 95% CI: 0.97-3.84) and advanced tumor grade (OR: 1.74, 95% CI: 0.95-3.18). By this study, we conclude that OPN overexpression indicates a poor prognosis for patients with HCC, it may also have predictive potential for HCC invasion and metastasis.