Clinical significance of serum hepatocyte growth factor (HGF) levels in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. This study was conducted to investigate the serum levels of hepatocyte growth factor (HGF)in HCC patients and the relationship with tumor progression and known prognostic parameters. Fifty-four patients with HCC were investigated. Pretreatment HGF levels were employed the quantitative sandwich enzyme immunoassay technique (ELISA). Age and sex matched 20 healthy controls were included in the analysis. The median age of the patients was 60 years (range 36–77 years); where males consistituted of majority of the group (88.8 %). All of patients had cirrhotic history. Fourty-six percent (n?=?25) of patients had Child-Pugh Score A, 30 % (n?=?16) had Score B or C. All of the patients were treated with local therapies but none of them received sorafenib. The baseline serum HGF levels were significantly higher in patients with HCC than in the control group (p?<?0.001). Male patients had higher serum HGF levels compared with female patients (p?=?0.01). Serum HGF levels were significantly higher in the patients with elevated serum ALT levels than others with normal serum ALT levels (p?=?0.05). Poor performance status (p?<?0.001), viral etiology of cirrhosis (p?=?0.03), larger tumor size (p?=?0.01), lower serum hemogloblin levels (p?=?0.03), and not be treated for HCC (p?=?0.001) related to worse survival. However, serum HGF did not have significantly adverse effect on survival (p?=?0.58). Despite serum HGF levels were found diagnostic value, serum HGF levels had no prognostic value in patients with HCC.     

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer

Insulin-like growth factor-1 (IGF-1) and its primary binding protein IGFBP-3 play an important role in cellular proliferation, differentiation, and apoptosis in many tumors, including ovarian cancer. The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich ELISA method. Twenty age- and sex-matched healthy controls were included in the analysis. Median age of patients was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced disease (FIGO stage III–IV; 90 %). No significant difference was observed in baseline serum IGF-1 and IGFBP-3 levels between EOC patients and healthy controls (p?=?0.99 and p?=?0.80, respectively). The young patients had higher serum IGF-1 and IGFBP-3 concentrations (p?=?0.04 and p?=?0.02, respectively). Patients with normal CA-125 levels had higher serum IGFBP-3 concentrations compared with those with higher CA-125 levels (p?=?0.008). However, no other clinical variables including histology, tumor grade, stage of disease, and response to chemotherapy were found to be correlated with serum IGF assays (p?>?0.05). A trend to significant relationship was found between the serum levels of IGF-1 and IGFBP-3 (r _s?=?0.212, p?=?0.07). The patients with elevated serum IGF-1 levels had favorable progression-free and overall survivals than those with lower levels (p?=?0.04 and p?=?0.03, respectively). However, serum IGFBP-3 concentrations were found to have no prognostic role for both survivals (p?=?0.12 and p?=?0.26, respectively). In conclusion, elevated serum level of IGF-1 is associated with favorable progression-free and overall survivals in EOC patients.     

Clinical significance of serum epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in patients with epithelial ovarian cancer

Cellular adhesion molecules might be good markers in some types of malignant tumors, useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of epithelial cell adhesion molecule (EPCAM) and vascular cell adhesion molecule-1 (VCAM-1) in epithelial ovarian cancer (EOC) patients. Fifty patients were enrolled into the study. Serum EPCAM and VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of the patients was 56.5 years, range 22 to 83 years. Majority of the patients had advanced disease (stages III–IV) (90 %). The baseline serum EPCAM levels of the EOC patients were significantly higher than in those in the control group (p?=?0.03). However, there was no significant difference in the serum VCAM-1 level between EOC patients and controls (p?=?0.24). Metastatic patients had higher serum VCAM-1 levels compared with the non-metastatic patients (p?=?0.03). Moreover, no other clinical variables including response to chemotherapy were found to be correlated with both serum assays (p?>?0.05). No correlation was found between serum EPCAM and VCAM-1 levels in EOC patients (r _s?=?0.105, p?=?0.362). Neither serum EPCAM level nor serum VCAM-1 level had significant adverse effect on survival. In conclusion, the higher baseline serum levels of VCAM-1 were associated with metastatic disease, and serum EPCAM level was found to be a diagnostic marker in EOC patients. However, both serum assays had no prognostic roles on outcome.     

Is there any diagnostic value of serum protease-activated receptor-1 (PAR1) levels on determination of epithelial ovarian carcinoma?

The role of molecular markers in ovarian cancer is still a matter of debate. Protease-activated receptor-1 (PAR1) might be a good marker in some types of malignant tumors and might provide useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of PAR1 in regard to diagnostic, predictive, and prognostic value in epithelial ovarian cancer (EOC) patients. Forty-four EOC patients were enrolled in this study. Serum PAR1 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. Twenty-five age- and sex-matched healthy controls were included in the analysis. The median age of patients was 58 years old, ranging from 22 to 83 years, where most of them had advanced disease (stage III–IV) (n?=?40, 91 %). The median serum PAR1 values were significantly elevated in patients compared to healthy controls (1.52 ng/ml vs. 1.13 ng/ml) (p?=?0.03), whereas any clinical variables including response to chemotherapy did not associate with serum assay (p?>?0.05). Progression-free survival (PFS) and overall survival (OS) of patients who did not respond to chemotherapy nor had platinum resistance in relapsed disease were poorer in the analyses. On the other hand, serum PAR1 levels showed no significant adverse effect on either PFS or OS (p?=?0.43 and p?=?0.49, respectively). These results proved that baseline serum PAR1 levels of patients with EOC were significantly higher than those of healthy people. However, these assays suggested no predictive or prognostic value in this group of patients.     

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with breast cancer

Insulin-like growth factor-1 (IGF-1) and its primary binding protein-3 (IGFBP-3) play an important role in cellular proliferation, differentiation and apoptosis in many tumors, including breast cancer (BC). The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in BC patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) methods. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of diagnosis was 48 years (range: 29–80). Thirty-seven (39 %) consisted of metastatic disease. No significant difference in baseline serum was found in both IGF-1 and IGFBP-3 levels between BC patients and healthy controls (p?=?0.92 and p?=?0.26, respectively). None of the prognostic parameters analyzed was correlated significantly with the serum assay concentrations. Likewise, no correlations were also found between these serum concentrations and response to chemotherapy. No significant correlation was found between serum IGF-1 and IGFBP-3 levels in BC patients (r _s?=?0.048, p?=?0.66).The patients with elevated serum IGF-1 levels had favorable in survival than those with lower levels (p?=?0.05). However, serum IGFBP-3 concentrations were found no prognostic role for outcome (p?=?0.35). In conclusion, elevated serum IGF-1 level is afavorable prognostic factor for overall survival in BC patients.     

A phase I trial of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer

The mammalian target of rapamycin (mTOR) plays a critical role in promoting tumor cell growth and is frequently activated in breast cancer. In preclinical studies, the antitumor activity of mTOR inhibitors is attenuated by feedback up-regulation of AKT mediated in part by Insulin-like growth factor type 1 receptor (IGF-1R). We designed a phase I trial to determine the maximum-tolerated dose (MTD) and pharmacodynamic effects of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer refractory to standard therapies. A 3 + 3 Phase I design was chosen. Temsirolimus and Cixutumumab were administered intravenously on days 1, 8, 15, and 22 of a 4-week cycle. Of the 26 patients enrolled, four did not complete cycle 1 because of disease progression (n = 3) or comorbid condition (n = 1) and were replaced. The MTD was determined from the remaining 22 patients, aged 34–72 (median 48) years. Most patients (86 %) had estrogen receptor positive cancer. The median number of prior chemotherapy regimens for metastatic disease was 3. The MTD was determined to be Cixutumumab 4 mg/kg and temsirolimus 15 mg weekly. Dose-limiting toxicities (DLTs) included mucositis, neutropenia, and thrombocytopenia. Other adverse events included grade 1/2 fatigue, anemia, and hyperglycemia. No objective responses were observed, but four patients experienced stable disease that lasted for at least 4 months. Compared with baseline, there was a significant increase in the serum levels of IGF-1 (p < 0.001) and IGFBP-3 (p = 0.019) on day 2. Compared with day 2, there were significant increases in the serum levels of IGF-1 (p < 0.001), IGF-2 (p = 0.001), and IGFBP-3 (p = 0.019) on day 8. A phase II study in women with metastatic breast cancer is ongoing.     

Increased serum level of thymidine kinase 1 correlates with metastatic site in patients with malignant melanoma

Thymidine kinase 1 (TK1) is involved in cancer progression. Metastatic site is a prognostic factor in melanoma. We assessed whether serum levels of TK1 are associated with metastatic sites or prognosis in patients treated for stage IV melanoma. The study included 64 patients, who received dacarbazine or four-drug chemotherapy (dacarbazine, vincristine, bleomycin, and lomustine) both combined with interferon-alfa. Serum samples for TK1 were analyzed by ELISA. The patients (n?=?22) with only skin and subcutaneous metastases had significantly lower mean TK1 levels (1,639 pg/ml) than the patients (n?=?42) with other distant metastases (2,586 pg/ml, Mann–Whitney, p?=?0.031). TK1 levels above the median (1,590 pg/ml) were significantly related to deep lymph node involvement (odds ratios 3.672; 95 % confidence intervals 1.024–12.843, p?=?0.036). There were no other significant associations between TK1 levels and tumor burden nor were the levels significantly related to the response to therapy or survival. Those eight patients who had received previous adjuvant IFN-alfa therapy had lower mean TK1 levels (1,735 pg/ml) as compared to those 56 patients without previous IFN-alfa therapy (2,338 pg/ml, analysis of variance, p?=?0.026). This is the first study exploring serum TK1 in melanoma. TK1 might be involved in the deep lymphatic dissemination and progression of melanoma metastasis.     

Serum levels of osteopontin as a prognostic factor in patients with oral squamous cell carcinoma

Osteopontin (OPN) is a multifunctional glycophosphoprotein that was detected in many carcinomas, and it may have a prognostic role. The aim of this study was to determine osteopontin serum levels in patients with oral squamous cell carcinoma (OSCC) and investigated its correlation with clinicopathological features of tumor. Using an ELISA kit, we assessed and compared the circulating levels of OPN in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. The serum osteopontin level in patients with OSCC was significantly higher (145.8?±?14.6 ng/ml, n?=?45) compared with the healthy controls (53.9?±?9.6 ng/ml, n?=?45, p?<?0.001). Mean serum osteopontin level was significantly higher in patients with nodal metastasis (p?=?0.03) and higher stage (p?=?0.02). Findings of the present study suggest that OPN may have a potential role in pathogenesis of OSCC and it may be used as a tool for monitoring tumor progression.     

Clinical significance of serum transforming growth factor-beta 1 (TGF-β1) levels in patients with epithelial ovarian cancer

Transforming growth factor-beta 1 (TGF-β1) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-β1 in epithelial ovarian cancer (EOC) patients. A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum TGF-β1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty age- and sex-matched healthy controls were included in the analysis. Median age of patients was 56.5 years old (range 22 to 83 years). Majority of the patients had advanced disease (FIGO stage III–IV; 90 %). There was no significant difference in baseline serum TGF-β1 levels between EOC patients and the controls (p?=?0.39). A trend to significant relationship was found between the serum levels of TGF-β1 and stage of disease (p?=?0.06). The elevated serum TGF-β1 level was associated with metastatic disease. The other known clinical variables including histology, grade of histology, debulking surgery, and serum CA 125 levels were not found to be correlated with serum TGF-β1 concentrations (p?>?0.05). Only the chemotherapy-unresponsive patients had higher serum TGF-β1 levels compared with responsive ones (p?=?0.02). Serum TGF-β1 concentration was found to have no prognostic role for both progression-free and overall survivals (p?=?0.42 and p?=?0.09, respectively). In conclusion, although the serum level of TGF-β1 has no diagnostic and prognostic role, it is associated with sensitivity to standard chemotherapy in EOC patients.     

Clinical significance of serum M30 and M65 levels in metastatic pancreatic adenocarcinoma

M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was conducted to investigate the serum levels of M30 and M65 in patients with metastatic pancreatic adenocarcinoma (MPA) and the relationship with tumor progression and known prognostic parameters. Twenty-six patients with MPA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum M30 and M65 levels were determined using enzyme-linked immunosorbent assay. The median age at diagnosis was 59 years, range 32–80 years; 14 patients were men. All patients had metastatic stage, and most (n?=?21, 81 %) had hepatic metastasis. The baseline levels of both serum M30 and serum M65 were significantly higher in patients with MPA than those in the control group (p?<?0.001, for both assays). Serum M65 level was only significantly higher in the patients with elevated serum LDH levels than in others with normal serum LDH levels (p?=?0.03). For serum M30 levels, no correlation was found. The significant relationship was found between the serum levels of M30 and M65 (r _s?=?0. 926, n?=?26, p?<?0.001, Spearman’s correlation). The median survival for all patients was 31.7?±?2.2 weeks (95 % CI?=?27.31–36.08). Although only the serum LDH level was found to be a significant prognostic factor (p?=?0.01), neither serum M30 nor serum M65 had significant effect on survival (p?=?0.28 and p?=?0.15, respectively). In conclusion, although both serum levels of M30 and M65 assays were found to be of diagnostic value, no predictive and prognostic values were determined in MPA patients.     

NORE1A sensitises cancer cells to sorafenib-induced apoptosis and indicates hepatocellular carcinoma prognosis

NORE1A, identified as a Ras effector, is frequently silenced in human cancers and has been implicated in tumour progression. Reports showing that NORE1A may function as a tumour suppressor have been emerging. However, to date, its expression and relevant significance in hepatocellular carcinoma (HCC) remain elusive. In this study, we examined the expression of NORE1A in HCC cell lines and a cohort of 250 HCC samples. We found that both the mRNA and the protein levels of NORE1A were noticeably downregulated in 14 fresh HCC tissues, compared to corresponding paracarcinoma tissues. Furthermore, NORE1A in tumours was decreased in 72.4 % (181/250) of HCC patients. Low NORE1A expression was significantly associated with poor differentiation (P?=?0.003), advanced stage (P?=?0.002), high level of serum AFP (P?<?0.001), vascular invasion (P?=?0.034) and incomplete involucrum (P?=?0.018). Multivariate analysis revealed that NORE1A was an independent poor prognostic factor for both overall survival (hazard ratio (HR) 0.622, 95 % confidence interval (95 % CI) 0.405–0.956, P?=?0.030) and recurrence-free survival (HR 0.613, 95 % CI 0.390–0.964, P?=?0.034). Moreover, low NORE1A expression in advanced-stage HCC predicted disease relapse. In addition, NORE1A overexpression reduced cell viability, inhibited colony formation, and attenuated cell invasion in vitro. Further study demonstrated that NORE1A was capable of sensitising cancer cells to sorafenib-induced apoptosis via the activation of the Mst-1/Akt pathway. Collectively, our data suggest that NORE1A may be a promising prognostic biomarker and therapeutic target in HCC.     

Human papillomavirus is independent prognostic factor on outcome of oropharyngeal squamous cell carcinoma

The primary aim of this study is to assess differences in patients’ clinicopathological characteristics based on human papillomavirus (HPV) status and the effect of HPV status on outcome in oropharyngeal squamous cell carcinoma (OSCC). The medical registry of 81 patients who were treated for OSCC was retrospectively analyzed. Factors that are found to be predictive of poor overall survival and event risk by univariate Cox’s regression analysis included age greater than 60 years (hazard ratio (HR), 1.2, p?=?0.02, and HR, 1.12, p?=?0.05), poor Eastern Cooperative Oncology Group performance (HR,1.6, p?=?0.01, and HR,1.32, p?=?0.001), advanced T stage (HR,1.38, p?=?0.01, and HR,1.4, p?=?0.02), advanced N stage(HR, 1.6, p?=?0.03, and HR,1.5, p?=?0.03), smoking history (HR,1.4, p?=?0.04, and HR, 1.6, p?=?0.03), and HPV-negative patients (HR, 2.4, p?=?0.012, and HR, 1.8, p?=?0.01). HPV-positive tumors were estimated to have a 36 % reduction in risk of death and 32 % reduction in event risk. HPV status had independent prognostic effects on survival and event-free survival.     

The diagnostic,predictive, and prognostic role of serum epithelial cell adhesion molecule (EpCAM) and vascular cell adhesion molecule-1 (VCAM-1) levels in breast cancer

The purpose of this study was to determine the clinical significance of vascular cell adhesion molecule-1 (VCAM-1) and epithelial cell adhesion molecule (EpCAM) in breast cancer (BC) patients. Ninety-six BC patients and 30 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich (enzyme-linked immunosorbent assay (ELISA)). The median age at diagnosis was 48 years (range 29–80 years). Majority of the patients (71 %) had luminal subtype, and 38.5 % had metastatic disease. Twenty-nine (30 %) patients showed tumor progression, and 20 (21 %) patients died during follow-up. Median progression-free survival (PFS) and overall survival (OS) were 8.6?±?1.7 and 35.5?±?1.5 months, respectively. The baseline serum EpCAM levels of the patients were significantly higher than those of the controls (p?VCAM-1 between the patients and controls (p?=?0.47). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p?>?0.05). Patients with HER-2-positive and triple-negative tumors had significantly poorer PFS (p?=?0.04 and p?=?0.001, respectively), while metastatic disease and chemotherapy unresponsiveness had significantly adverse effect on OS analysis (p?p?VCAM-1 levels nor serum EpCAM levels were identified to have a prognostic role on either PFS or OS (VCAM-1 p?=?0.76 and p?=?0.32; EpCAM p?=?0.16 and p?=?0.69, respectively). Even though any predictive or prognostic role could not be determined for both markers, serum levels of EpCAM were found to have diagnostic value in BC patients.     

Clinical and Prognostic Significance of Coagulation Assays in Gastric Cancer

Purpose

Activation of coagulation and fibrinolysis is frequently found among cancer patients. Such tumors are considered to be associated with a higher risk of invasion, metastases, and eventually, worse outcome. The aim of this study is to explore the clinical and prognostic value of blood coagulation tests in gastric cancer (GC) patients.

Materials and Methods

A total of 44 consecutive patients with a pathologically confirmed diagnosis of GC were enrolled into the study. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were evaluated. Control group comprised 50 age- and sex-matched individuals without history of malignancy and coagulation disorder.

Results

Median age at diagnosis was 55 years, range 19–80 years; most had men (n?=?32, 73 %) and metastatic disease (n?=?31, 70 %). The level of blood coagulation tests showed a statistically significant difference between the patient and the control groups (P?<?0.001 for all, but p?=?0.07 for PT). DD levels were significantly associated with elevated PLT and LDH levels (p?=?0.009 and p?=?0.01, respectively). Patients with metastatic disease had higher levels of F (p?=?0.001) and INR (p?=?0.027) levels. Elevated DD levels tended to be a poor prognostic factor on outcome (p?=?0.06).

Conclusion

Change in almost all coagulation tests are found in GC patients and only DD level seems to be of prognostic value.     

Rsf-1 overexpression serves as a prognostic marker in human hepatocellular carcinoma

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 and its clinical significance in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed the expression pattern of Rsf-1 in human HCC tissues and found that Rsf-1 was overexpressed in 41.1 % of HCC specimens. There was a significant association between Rsf-1 overexpression and tumor stage (p?=?0.0322), AFP (p?=?0.0184), and tumor relapse (p?=?0.0112). Furthermore, Rsf-1 overexpression correlated with poor overall survival in HCC patients (p?p?=?0.0079). Small interfering RNA (siRNA) knockdown in SK-Hep-1 cells with high endogenous Rsf-1 expression inhibited cell proliferation and colony formation, with downregulation of cyclin E protein. In conclusion, Rsf-1 is overexpressed in HCCs and serves as a novel tumor marker. Rsf-1 contributes to hepatocellular carcinoma cell growth through regulation of cell cycle proteins.     

Are high initial CEA and CA 19–9 levels associated with the presence of K-ras mutation in patients with metastatic colorectal cancer?

In certain cell culture studies, significant CEA expression was observed in K-ras mutant cells. However, the relationship between high CEA levels and K-ras status has not been sufficiently investigated. In the present study, we aimed to determine the prognostic role of initial CEA and CA 19–9 values in metastatic colorectal cancer patients according to the status of K-ras. Between 2000 and 2010, a total of 215 patients with metastatic colorectal cancer who were treated and followed up in our oncology center were analyzed. Smokers were excluded from the study. The clinicopathological findings and initial CEA and CA19-9 values were determined. K-ras mutation analysis was performed using quantitative PCR evaluation of the DNA from the tumor tissues. Eighty-two patients (38.1 %) were female and 133 (61.9 %) were male, with a median age of 59 years (range 27–83). Based on tumor localization, 127 patients (59 %) were classified as colon cancer patients and 88 patients (41 %) were classified as rectal cancer patients. The majority of patients (83.3 %) had pure adenocarcinoma histology, while 36 cases (16.7 %) had mucinous adenocarcinoma. The initial CEA levels were detected to be high (>5 ng/mL) in 108 of the patients (50.2 %), while high levels of initial CA 19–9 (>37 ng/mL) were found in 90 patients (41.8 %). K-ras mutations were detected in 99 of the patients (46 %). K-ras was found to be wild type in 116 patients (54 %). Significant differences were detected between the K-ras wild-type and mutant groups with respect to age and the initial serum CEA levels. Patients with K-ras mutations were younger (p?=?0.04) and had higher initial CEA levels (p?=?0.02) compared to patients with K-ras wild type. The median overall survival (OS) time and 3-year OS rate for patients with a high initial CEA level (>5 ng/mL) were significantly shorter than those of patients with a low initial CEA level (<5 ng/mL) (50.5 months and 61.8 % vs. 78.6 months and 79.1 %, p?=?0.014). Furthermore, the patients with low initial CA 19–9 levels (<37 ng/mL) had a significant better median OS interval and 3-year OS rate (76.1 months and 80.1 %) compared to patients with high initial CA 19–9 levels (>37 ng/mL) (37.6 months and 55.7 %, p?=?0.04). Multivariate analysis indicated that stage at the time of diagnosis (p?<?0.001) and low initial serum CEA level (p?=?0.037) were independent prognostic factors of OS. For K-ras mutant patients, the stage at diagnosis (p?=?0.017), low initial serum CEA level (p?=?0.001), and low initial serum CA 19–9 level were found to be independent prognostic indicators of OS. Our findings demonstrate for the first time that the presence of a K-ras mutation correlated with high initial CEA and CA 19–9 levels in patients with metastatic colorectal cancer. Patients with high initial CEA and CA 19–9 levels may potentially predict the presence of a K-ras mutation, and this prediction may guide targeted therapies in these patients.     

IGF-1R and Bmi-1 expressions in lung adenocarcinoma and their clinicopathologic and prognostic significance

IGF-1R and Bmi-1 play a critical role in cancer growth and survival. We explored the correlation between IGF-1R and Bmi-1, as well as their relationship with clinicopathological parameters and their impacts on outcomes in patients with lung adenocarcinoma resected. Tumors from 178 surgical lung adenocarcinoma patients were evaluated for IGF-1R and Bmi-1 expression by means of immunohistochemistry. The clinicopathological implications of these molecules were analyzed statistically. There was a significant correlation between the expression of IGF-1R and Bmi-1 (p?=?0.011). The 5-year survival rate of patients with Bmi-1 positive was only 31.2 %, but patients with Bmi-1 negative had a survival rate of 50.7 % (p?=?0.004). The pattern of survival curves showed that Bmi-1 was a significant prognostic factor of poor overall survival in lung adenocarcinoma patients. However, there was no obvious correlation between IGF-1R expression and patient survival. The results of multivariate Cox analysis revealed that the pathological stages and Bmi-1 expression were independent prognostic factors. Therefore, Bmi-1 may be a good biomarker to predict the prognosis of patients with completely resected lung adenocarcinoma.