血清E-钙黏连蛋白对肝细胞癌患者预后的预测价值

目的 探讨血清可溶性E-钙黏连蛋白(sEC)对肝细胞癌患者预后的预测价值.方法 选取40例肝细胞癌患者为观察组,行腹腔镜解剖性肝段切除术,选取40例健康体检者为对照组.总结观察组患者的围术期结果,比较对照组血清sEC与观察组围术期血清sEC.结果 观察组中,5例患者中转开腹,其中2例患者因肝中静脉损伤,3例患者因肝实质深部出血腔镜下止血困难;35例患者成功施行腹腔镜解剖性肝段切除术,观察组术后复发时血清sEC水平高于观察组术后和对照组(P﹤0.05).结论 血清sEC对肝细胞癌患者的预后具有一定的预测价值.     

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。     

Prognostic implications of ezrin expression in human hepatocellular carcinoma

Ezrin is known to regulate cellular survival, adhesion, migration, and invasion and has been identified as one of the key components of tumor progression and metastasis. The authors investigated ezrin expression in human hepatocellular carcinoma (HCC) and sought to determine its relation with clinicopathologic parameters, patients' outcome, and interacting molecular markers. Ezrin expression was assessed by immunohistochemical staining in 100 surgically resected HCCs using the tissue microarray method. A total of 28 HCCs showed high ezrin immunoreactivity, mainly in cytoplasm. Ezrin expression exhibited a positive correlation with c‐Met expression (P = 0.001), but showed no correlation with the expression of CD44s or E‐cadherin. HCCs expressing high level of ezrin were significantly associated with advanced TNM stage, poor Edmondson's histological grade, macroscopic portal vein invasion, tumor recurrence, and extrahepatic recurrence (P < 0.05). Univariate analysis showed that HCCs with high ezrin immunoreactivity were strongly associated with unfavorable overall and disease‐free survivals than HCCs with low or negative for ezrin immunoreactivity (P = 0.0001 and 0.0011, respectively). Furthermore, multivariate analysis demonstrated that a high level of ezrin expression was independently associated with poor overall survival (hazard ratio, 1.905; P = 0.011). The results suggest that ezrin expression could be a potential predictive marker of progression, metastasis, and prognosis in HCC. © 2010 Wiley‐Liss, Inc.     

Prognostic value of serum biological markers in patients with hepatocellular carcinoma.

PURPOSE: Prognosis of patients with hepatocellular carcinoma (HCC) is assessed by using indexes based on clinical and instrumental parameters. The Cancer of the Liver Italian Program (CLIP) staging system combines the Child-Pugh classification with tumor size, portal invasion, and alpha-fetoprotein and predicts the outcome of HCC patients more precisely than the Okuda staging system. Serum levels of a number of biological variables have been found to be increased in patients with HCC and are associated with different outcomes. Our aims in this study were to test the prognostic role of the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), interleukin 6 (IL-6), and anti-p53 and to assess whether the addition of any of the above serum markers could further improve the predictive ability of the CLIP score. EXPERIMENTAL DESIGN: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 were assayed in 80 patients with HCC and correlated with their outcomes. Nonparametric procedures were applied to test correlations between serum sICAM-1, sIL-2R, IL-6, anti-p53, and other prognostic factors. For survival analyses, the product-limit method, log-rank test, and Cox proportional hazards model were applied. RESULTS: Only serum levels of sIL-2R correlated with survival, which was longer for patients with lower values (< or =950 units/ml). However, with multivariate analysis sIL-2R did not confirm its predictive role when tested with the CLIP score as a covariate, with a hazard of death of 1.51 (95% confidence interval, 0.76-3.01). CONCLUSIONS: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 are not useful as prognostic factors for HCC in clinical practice. They do not improve the predictive ability of the CLIP score.     

hMLH1 and hMSH2 expression in human hepatocellular carcinoma

The role of microsatellite instability (MSI) in the pathogenesis of hepatocellular carcinoma (HCC) is incompletely defined. Although high-frequency MSI (MSI-H) is infrequently seen in HCC, some studies have suggested a role for MSI in HCC development. While MSI has been clearly defined for a subset of tumors, in particular colorectal, gastric and endometrial cancers, generally accepted criteria have not been developed for other tumors. Colorectal cancers (CRC) are classified as MSI-H if >30-40% of >5 microsatellite loci analyzed show instability. The MSI-H phenotype is associated with defective DNA mismatch repair (MMR) and is observed in the majority of tumors from patients with hereditary non-polyposis colon cancer (HNPCC) and also in 15% of sporadic CRCs. Inactivating mutations of the hMLH1 or hMSH2 genes lead to defects in MMR in HNPCC. In sporadic CRCs, MMR is usually due to hypermethylation of the hMLH-1 promoter. The role of defective MMR in hepatocellular carcinogenesis is controversial. Immunohistochemistry for hMLH1 and hMSH2 reliably indicates hMLH1 or hMSH2 loss in MSI-H CRC tumors. To investigate the role of defective MMR in HCC carcinogenesis, we performed immunohistochemistry for hMLH1 and hMSH2 on 36 HCCs. BAT26, a microsatellite marker that reliably predicts MSI-H was also examined. All 36 of the tumors stained positively for both hMLH1 and hMSH2, strongly suggesting an absence of either inactivating mutations of hMLH1 and hMSH2 or promoter hypermethylation of hMLH1. None of the tumors showed MSI at the BAT26 locus. These findings suggest that defective MMR does not contribute significantly to hepatocellular carcinogenesis.     

Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma

Aims To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC).Design Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression.Results Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin–bilirubin (ALBI) score, liver–spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD.Conclusions Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.Subject terms: Hepatocellular carcinoma, Prognostic markers     

Prognostic value of tumor-infiltrating FOXP3 regulatory T cells in patients with hepatocellular carcinoma

Aims

CD4⁺ CD25⁺ forkhead box P3 (FOXP3)⁺ T_reg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (T_reg), we conducted a retrospective study on 164 patients with hepatocellular carcinoma (HCC) who underwent curative hepatic resection.

Methods

We investigated the number of tumor-infiltrating FOXP3⁺ T_reg in formalin-fixed HCC specimens. The number of FOXP3⁺ T_reg for each case was calculated as the total number of positive cells per 10 high-power fields (HPF) on light microscopy. Long-term survival rate after resection according to the number of FOXP3⁺ T_reg was accessed by univariate and multivariate analyses.

Results

The mean and median numbers of tumor-infiltrating T_reg were 29.0 and 14 per 10 HPF for FOXP3⁺ T_reg. The number of FOXP3⁺ T_reg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high T_reg counts (≥14, n = 84) than in those with low T_reg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high T_reg counts, presence of portal vein invasion, and elevation of preoperative aspartate aminotransferase level were independent predictive factors of tumor recurrence.

Conclusions

The high number of tumor-infiltrating T_reg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.     

Prognostic value of splenic volume in hepatocellular carcinoma patients receiving transarterial chemoembolization

BackgroundLiver function is a key determinant for the survival of hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE). However, establishing robust prognostic indicators for liver insufficiencies and patient survival remains an unmet demand. This retrospective study evaluated the prognostic value of splenic volume (SV) in HCC patients undergoing TACE.MethodsA total of 67 HCC patients who underwent at least two consecutive TACE procedures were retrospectively included in this study. Comprehensive clinical information and follow-up data were collected, and the SV was measured based on dynamic contrast enhanced images. Risk factors of SV enlargement were assessed. The prognostic value of SV on survival was analyzed and compared with Child-Pugh (CP) classification and albumin-bilirubin (ALBI) grade.ResultsThe baseline SV was 299.74±143.63 cm³, and showed a moderate and statistically significant correlation with CP classification (R=0.31, P<0.05). The SV increased remarkably after the first and second TACE procedures (330.16±155.38 cm³, P<0.01, and 355.63±164.26 cm³, P<0.01, respectively). In survival analysis, the optimal cut-off value of SV was determined as 373 cm³ using X-tile software, and the patients were divided into the small SV group and the large SV groups accordingly. Based on the pre-TACE SV, the median overall survival (mOS) for patients in the small SV group and the large SV group was 458 days and 249 days, respectively (P<0.05). After the first and second TACE, the mOS in the small SV group and the large SV group were 454 vs. 266 days (P<0.05) and 526 vs. 266 days (P<0.05), respectively. No prognostic value of CP classification and ALBI grade was identified for these patients. Furthermore, there were no significant differences between the small and large SV groups in age, tumor stage, and ALBI grade, except for CP classification (P<0.05).ConclusionsSV was correlated with CP classification and was a robust predictor for HCC patients undergoing TACE treatment.     

Prognostic value of soluble MICA levels in the serum of patients with advanced hepatocellular carcinoma

Serum levels of soluble MHC class I-related chain A (sMICA) are related with the prognosis of various types of cancer; however, few studies on the prognostic value of sMICA in hepatocellular carcinoma (HCC) have been reported. In this study, we retrospectively investigated the relationship between sMICA levels and clinical features of advanced HCC, and we assessed the prognostic value of sMICA in advanced HCC. Furthermore, the relationship of serum sMICA levels and natural killer group 2, member D (NKG2D) expression on natural killer (NK) cells was also evaluated. We detected sMICA levels in the serum of 60 advanced HCC patients using enzyme-linked immunosorbent assay (ELISA) and measured expression levels of NKG2D on NK cells using flow cytometry. We found that serum sMICA levels in HCC patients were in the range of 0.10 -6.21 ng/mL. Chi-square analyses showed that sMICA level was significantly related with only tumor size. Survival analysis showed that a high sMICA level was significantly related with poor prognosis among HCC patients. Multivariate analyses indicated that sMICA was an independent prognostic factor. In addition, the levels of CD56+NKG2D+NK cells were within the range of 11.2%-55.4%, and correlation analyses indicated that sMICA level was negatively correlated with the level of NKG2D+NK cells. Our results suggest that serum sMICA levels may be an independent prognostic factor for advanced HCC.     

Prognostic value of preoperative peripheral monocyte count in patients with hepatocellular carcinoma after liver transplantation

Tumor Biology - Prognostic value of peripheral monocyte, as a member of inflammatory cells, was widely being investigated. The aim of this study was to evaluate the prognostic value of preoperative...     

Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma

203 primary human lung tumours, of which 119 were adenocarcinoma and 84 were squamous cell carcinoma, were investigated immunohistochemically for the expression of c-erbB-2 protein. Positive staining was evident in 33 (28%) of adenocarcinomas and 2 (2%) of squamous cell carcinomas. In cases of adenocarcinoma, c-erbB-2 was present in 18% of those with stage I disease. In stage IIIA, stage IIIB and stage IV cases, c-erbB-2 was present in 39%, 50% and 60%, respectively (I vs. IIIA and I vs. IIIB: P < 0.05, I vs. IV: P < 0.01). The 5-year survival rates of c-erbB-2 positive patients and those who were negative were 30% and 52%, respectively, with a statistically significant difference (P < 0.01). These observations suggest that when the expression of c-erbB-2 correlates with invasiveness of the tumour, this correlation may serve as a prognostic indicator, particularly in cases of adenocarcinoma of the lung.     

Akt2 expression correlates with prognosis of human hepatocellular carcinoma

Akt, a down-stream target of phosphatidylinositol-3 kinase, plays multiple roles in carcinogenesis. To elucidate its role in hepatocarcinogenesis, we immunohistochemically investigated the expression of Akt protein (Akt1 and Akt2) in tumor and non-tumor tissues from 56 patients with hepatocellular carcinoma (HCC). High expression of Akt2 in HCC tissues was detected in 21 cases (38%) while Akt1 expression was moderate or less in all cases. Low expression of Akt2 was associated with histopathological differentiation, portal invasion and number of tumor nodules (p=0.026, 0.023, and 0.001, respectively). Univariate analysis showed that Akt2, histopathological differentiation, and portal vein invasion were significant prognostic factors (p=0.001, 0.028, and 0.006, respectively). Multivariate analysis revealed that in addition to histopathological differentiation, Akt2 was an independent prognostic marker (risk ratio for cancer relapse, 6.35, p=0.012). In contrast, Akt1 expression did not correlate with any clinicopathological features. Our findings suggest that Akt2, but not Akt1, is a novel independent predictor for the development and progression of HCC.     

喉鳞状细胞癌中SIAH2表达的预后价值

  目的  观察E3泛素连接酶SIAH2在喉鳞状细胞癌组织中的表达, 探讨其在喉鳞状细胞癌中表达的预后价值。  方法  应用免疫组织化学染色法检测119例喉组织标本SIAH2的定性表达, Western blot方法检测喉新鲜组织中SIAH2的定量表达, 结合患者5年随访资料, 利用Kaplan-Meier法绘制生存曲线, Log-rank法分析SIAH2的表达水平与喉鳞状细胞癌患者预后的关系, Cox比例风险回归模型分析喉鳞状细胞癌患者预后的独立预测因素。  结果  SIAH2在喉鳞状细胞癌中阳性表达率为77.19%, 显著高于不典型增生(53.13%)和癌旁正常喉组织(26.67%), 差异具有统计学意义(χ2=21.02, P＜0.001)。SIAH2的表达与组织学分级、临床分期及淋巴结转移相关(均P＜0.05);在正常喉组织(1.25±0.04)、不典型增生(1.38±0.05)及喉鳞状细胞癌组织(1.44±0.07)中SIAH2的相对表达量逐渐升高(F=61.811, P＜0.001);SIAH2阳性与阴性患者的5年生存率分别为18.18%和58.33%(χ2=5.720, P= 0.017), SIAH2阳性与阴性患者的中位生存时间分别为25个月和60个月(P＜0.05);多因素回归分析表明高表达SIAH2是喉鳞状细胞癌患者总生存期的独立预测因子。  结论  SIAH2可能作为一个癌基因参与喉鳞状细胞癌的发生发展, 过表达SIAH2与喉鳞状细胞癌患者的不良预后有关, 提示SIAH2作为一个潜在的靶基因可能对喉鳞状细胞癌的治疗有帮助。      

Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma.

PURPOSE: Human kallikrein 10 (hK10; also known as the normal epithelial cell-specific 1 gene and protein) is a secreted serine protease, which belongs to the human kallikrein family. It has been reported that hK10 is down-regulated in breast and prostate cancer cell lines and that it may function as a tumor suppressor. Recently, we developed a highly sensitive and specific immunoassay for hK10 and found that this protein is abundantly expressed in ovarian tissue. In this study, we measured quantitatively hK10 levels in ovarian cancer cytosolic extracts and evaluated the prognostic value of this biomarker in ovarian cancer. EXPERIMENTAL DESIGN: Specimens from eight normal ovarian tissues, eight ovarian tissues with benign disease, and 182 ovarian tumors were investigated. RESULTS: hK10 concentration in ovarian tumor cytosols ranged from 0 to 84 ng/mg of total protein, with a median of 2.6. This median was highly elevated in comparison with normal and benign ovarian tissues (P < 0.001). A cutoff of 1.35 ng/mg was selected to categorize tumors as hK10 high and hK10 low. With chi(2) test and Fisher's exact test, high concentration hK10 was found to be associated with advanced disease stage, serous histological type, suboptimal debulking, and large residual tumor (>1 cm; all P < 0.05). hK10 status was additionally correlated with clinical outcome, including progression-free (PFS) and overall survival (OS) using the Cox model. In univariate analysis, we found that patients with hK10 high tumors were more likely to die and relapse, in comparison with patients with hK10 low tumors (hazards ratios for PFS and OS were 1.93 and 2.42, respectively; P < 0.05). Although this correlation disappeared after the entire patient population was subjected to multivariate analysis, it remained significant in the subgroup of patients with stage III/IV ovarian cancer (hazards ratios for PFS and OS were 1.98 and 2.12, respectively; P < 0.05). CONCLUSIONS: Our results indicate that hK10 is a new, independent, unfavorable prognostic marker, especially for late-stage ovarian cancer.     

Prognostic value of HLA class I expression in patients with oral squamous cell carcinoma

Human leukocyte antigen (HLA) class Ⅰ molecules play a central role in anticancer immunity, but their prognostic value in oral squamous cell carcinoma (OSCC) remains unclear. We examined HLA class I expression in 2 distinct tumor compartments, namely, the tumor center and invasive front, and evaluated the association between its expression pattern and histopathological status in 137 cases with OSCC. Human leukocyte antigen class Ⅰ expression was graded semiquantitatively as high, low, and negative. At the invasive front of the tumor, HLA class I expression was high in 72 cases (52.6%), low in 44 cases (32.1%), and negative in 21 cases (15.3%). The HLA class I expression in the tumor center was high in 48 cases (35.0%), low in 58 cases (42.4%), and negative in 31 cases (22.6%). The 5‐year overall survival and disease‐specific survival rates were good in cases with high HLA class I expression at the invasive front; however, there was no significant difference in survival based on HLA class I expression in the tumor center. In addition, high HLA class I expression was correlated with high CD8⁺ T cell density, whereas negative HLA class I expression was correlated with low CD8⁺ T cell density at the invasive front. These results suggest that it is easier for CD8⁺ T cells to recognize presented peptides in the case of high HLA class Ⅰ expression at the tumor invasive front and could be a prognostic factor for OSCC.     

Prognostic value of proliferating cell nuclear antigen (PCNA) expression in unresectable hepatocellular carcinoma

Recent studies indicate that evaluation of cell proliferation in mallignant tumors may have prognostic value, but limited data are available on its expression in hepatocellular carcinoma. We therefore evaluated the prognostic tool of PCNA antigen expression on paraffin-embedded sections of 54 patients with hepatocellular carcinoma and concomitant cirrhosis. According to the number of positive cells, the PCNA expression ranged between 0.8 and 47%, and was divided into two groups (Group A, PCNA less than or equal to 5.5%; Group B, PCNA >5.5%). The two groups of patients were numerically well balanced. Median survival was 16 months for group A and 12 months for group B. According to the Cox multivariate analysis, PCNA expression (P=0.002),TNM stage (P=0.009) and ECOG performance status (P<0.001) significantly correlated with survival. In conclusion, PCNA antigen expression was found to be a significant prognostic faeature in unresectable hepatocellular carcinoma and may be a useful tool for future trials.