Diagnostic and prognostic potentials of microRNA-27a in osteosarcoma

AimGrowing evidence suggest that the microRNA (miR)-23a/24-2/27a cluster may play a crucial role in mammary tumorigenesis and act as a novel class of oncogenes. Among these members, miR-27a has been reported to promote proliferation, migration and invasion in human osteosarcoma cells. The aim of this study was to detect the serum levels of miR-27a in osteosarcoma patients and to investigate its associations with clinicopathological features and prognosis.MethodsmiR-27a levels in sera from 166 osteosarcoma patients and 60 healthy controls were detected by real-time quantitative RT-PCR. Then, the associations of serum miR-27a level with clinicopathological factors or survival of osteosarcoma patients were further evaluated.ResultsCompared to healthy controls, the serum levels of miR-27a were significantly increased in osteosarcoma patients (P < 0.001). Importantly, miR-27a could efficiently screen osteosarcoma patients from healthy controls (Area under receiver operating characteristic curve, AUC = 0.867). Then, high miR-27a expression was more frequently occurred in osteosarcoma patients with advanced clinical stage (P = 0.001), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.008). In Kaplan–Meier survival analysis, high miR-27a expression was a significant indicator for poor overall survival (P = 0.006) as well as poor disease-free survival (P = 0.01). Furthermore, multivariate analysis demonstrated that miR-27a expression was an independent and significant prognostic factor to predict overall survival (P = 0.01) and disease-free survival (P = 0.03).ConclusionmiR-27a expression may be elevated in sera of osteosarcoma patients and in turn contributes to aggressive progression of this malignancy. Detection of serum miR-27a levels may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients.     

Decreased expression of microRNA-148a predicts poor prognosis in ovarian cancer and associates with tumor growth and metastasis

ObjectiveMicroRNA-148a (MiR-148a) had been reported to take part in some cancer progresses, but its clinical significance in ovarian cancer had been rarely reported. The purpose of this study was to evaluate the prognostic value of miR-148a as well as its roles in ovarian cancer progression.MethodsRelative expression of miR-148a in the plasma specimens of ovarian cancer patients was detected by qRT-PCR. Chi-square test was used to analyze the relationship between miR-148a expression and clinical characteristics. The overall survival was analyzed by Kaplan-Meier method and Cox regression analysis was used to evaluate the prognostic value of miR-148a. In addition, the ovarian cancer cell line SKOV-3 was separately transfected with pcDNA3-microRNA-148a over-expression vector and pcDNA3 empty vector to detect the functional roles of miR-148a in ovarian cancer progression.ResultsDecreased level of plasma miR-148a was observed in ovarian cancer patients compared with healthy controls. The expression level was associated with histopathologic grade, TNM stage and lymph node metastasis (P < 0.05 for all). Besides, patients with high level of miR-148a had a longer survival time than those with low level (40.3 months vs 31.6 months, log rank test, P = 0.002). Cox regression analysis indicated that miR-148a might be a potential biomarker for ovarian cancer prognosis (HR = 1.699, 95%CI = 1.175-2.456, P = 0.005). Moreover, cell experiments confirmed that miR-148a could inhibit proliferation, migration and invasion of ovarian cancer cells.ConclusionMiR-148a may be a potential prognostic factor for ovarian cancer and it can suppress tumor progression.     

Prognostic value of miR-26a and HMGA1 in urothelial bladder cancer

BackgroundMicroRNA-26a (miR-26a) functions as a tumor suppressor by regulating its direct target gene high mobility group AT-hook 1 (HMGA1). This study was aimed to investigate the associations of differential expression of miR-26a and HMGA1 with tumor progression and prognosis in urothelial bladder cancer (UBC) patients.Materials and methodsOne hundred and twenty-six UBC patients were selected and quantitative real-time PCR was performed to detect the expression of miR-26a and HMGA1 mRNA in the respective tumors.ResultsOur data showed the decreased expression of miR-26a and the increased expression of HMGA1 mRNA in UBC tissues compared with corresponding non-cancerous tissues (both P < 0.001). Then, the expression levels of miR-26a in UBC tissues were negatively correlated with those of HMGA1 mRNA significantly (r = –0.72, P < 0.001). In addition, UBC patients with combined miR-26a downregulation and HMGA1 upregulation (miR-26a-low/HMGA1-high) more frequently had advanced pathological stage (P < 0.001) and high tumor grade (P < 0.001). Moreover, miR-26a-low/HMGA1-high expression was associated with a significantly shortest disease-free survival (P < 0.001) and overall survival (P < 0.001) of all miR-26a/HMGA1 combined expression groups. Furthermore, multivariate analysis indicated that miR-26a/HMGA1 expression was an independent prognostic factor for both disease-free survival and overall survival (both P = 0.001) in UBC patients.ConclusionInteraction between miR-26a and its target gene HMGA1 may contribute to the malignant progression of human UBC. Tumors with miR-26a downregulation in combination with high expression of HMGA1 showed a worse prognosis than the other tumors. Combined detection of their expression might be particularly helpful for surveillance of disease progression and treatment stratification.     

Expression of haptoglobin predicts recurrence in head and neck squamous cell carcinoma

BackgroundWe determined whether expression of haptoglobin by head and neck squamous cell carcinoma (HNSCC) cells is associated with prognosis.MethodsWestern blotting was carried out to investigate the expression of haptoglobin in oral cancer cell lines. We study patients with HNSCC without distant metastasis at diagnosis. Correlation between cellular haptoglobin and clinical characteristics of HNSCC was analyzed to assess the prognostic value of cellular haptoglobin level. Kaplan–Meier survival curves and log-rank test were used to evaluate differences in recurrence, distant metastasis, and overall survival rates between patients grouped according to cellular haptoglobin level in cancer tissues. The relationship of haptoglobin expression with survival was assessed using Cox proportional hazard models.ResultsWestern blotting analysis showed that haptoglobin protein was expressed in 4 oral cancer cell lines. The recurrence rate was higher in HNSCC patients with over-expression of haptoglobin (> 50%) (P = 0.045). Over-expression of haptoglobin was also associated with an increased risk for recurrence (hazard ratio [HR] 3.2; 95% confidence interval [CI], 1.127–8.895; P = 0.029) after adjusting for age, gender, disease site, stage, and treatment modality.ConclusionsAltogether, the data presented show that cellular expression of haptoglobin is closely related to recurrence rate in HNSCC patients. The elevated risk of relapse was confirmed in a multivariate analysis. The cellular expression of haptoglobin may be a prognostic factor in HNSCC.     

Expression of bcl-2 correlates with poor prognosis and modulates migration of nasopharyngeal carcinoma cells

BackgroundThe role of bcl-2 expression, bcl-2 inhibitor HA14-1, and matrix metalloproteinase (MMP)-2 is still unclear in nasopharyngeal carcinoma (NPC).MethodsFrom 1996 to 2000, 145 patients with newly diagnosed NPC who were treated with high dose radiotherapy were enrolled. The relationship between bcl-2 expression, TNM stage, and disease-specific survival was analyzed. Furthermore, the NPC cell line HONE-1 was used to confirm the relationship between bcl-2 and cell metastasis.ResultsAmong the 145 patients, 47 (32.4%) of them were bcl-2 positive. The expression of bcl-2 was significantly correlated with neck lymph node metastasis (p = 0.006), and patients with negative bcl-2 expression had better disease-free survival (p = 0.007). A Cox regression model revealed that only bcl-2 expression (p = 0.023) and stage IV (p = 0.043) were statistically significant in the prognosis of NPC. In vitro analysis also showed that treatment with the bcl-2 inhibitor HA14-1 exerted an inhibitory effect on migration and expression of MMP-2 in HONE-1 cells.ConclusionsBcl-2 expression represents an important and easily assayed prognostic factor, and it may play an important role in lymph node metastasis. Inhibition of the migration mediated by MMP-2 may be a key feature for the prevention of cancer metastasis.     

Prognostic value of miR-29a expression in pediatric acute myeloid leukemia

ObjectivesAs a member of miR-29 family, miR-29a can act as either oncogene or tumor suppressor. However, its expression patterns in acute myeloid leukemia (AML) are controversial according to previous studies. Thus, the aim of this study was to determine the expression and clinical significance of miR-29a in pediatric AML.MethodsExpression levels of miR-29a in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. The prognostic values of miR-29a in pediatric AML were also analyzed.ResultsCompared with normal controls, we demonstrated a significantly decreased expression of miR-29a in the bone marrow of pediatric AML patients (P < 0.001). The expression levels of miR-29a were significantly lower in French–American–British classification subtype M7 than in other subtypes (P < 0.001) and differed significantly across cytogenetic risk groups (P = 0.002) with high miR-29a expression among those with favorable karyotypes. Moreover, low miR-29a expression was significantly associated with shorter relapse-free (P < 0.001) and overall (P = 0.008) survival in pediatric AML patients. Cox proportional hazards multivariate analysis of the univariate predictors identified cytogenetic risk and miR-29a expression as independent prognostic factors for relapse-free survival and overall survival. More interestingly, the prognostic value of miR-29a expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics.ConclusionOur data indicate for the first time that the down-regulation of miR-29a was associated with advanced clinical features and poor prognosis of pediatric AML patients, suggesting that miR-29a down-regulation may be used as an unfavorable prognostic marker in pediatric AML.     

Inter-alpha-trypsin inhibitor heavy chain H4 as a diagnostic and prognostic indicator in patients with hepatitis B virus-associated hepatocellular carcinoma

ObjectivesInter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with various diseases. We evaluated the diagnostic and prognostic significance of serum ITIH4 levels in healthy controls and patients with chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC).Design and methodsThe study enrolled 300 individuals (50 healthy controls, 50 with CHB, 100 with HBV-associated cirrhosis, and 100 with HBV-associated HCC). Serum ITIH4 levels were determined by western blot analysis and expressed in densitometry units (DU).ResultsITIH4 levels were higher in CHB (mean: 252.96 DU) and liver cirrhosis (mean: 206.43 DU) patients than in healthy controls (mean: 75.92 DU) and HCC patients (mean: 92.86 DU) (P < 0.001). The area under the receiver operating characteristic curve was 0.71 for the diagnosis of HCC in patients with HBV-related liver disease. Multivariate Cox regression analysis showed that large tumor size (≥ 5 cm) was independently associated with overall survival (hazard ratio 5.894, 95% confidence interval 1.373–25.300, P = 0.017). A Kaplan–Meier survival analysis showed significantly worse survival among HCC patients with both low ITIH4 (< 80 DU) and a large tumor size compared to that among other HCC patients (P < 0.001), and among patients with high AFP (> 200 ng/mL) and low ITIH4 compared to that among other HCC patients (P = 0.041).ConclusionsSerum ITIH4 levels are reduced in HCC patients compared to that in CHB and cirrhosis patients, and low serum ITIH4 levels are associated with shorter survival in HBV-associated HCC patients.     

LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression

Large tumor suppressor 2 (LATS2) plays significant roles in tumorigenesis and cancer progression. This study was aimed to analyze the correlation between LATS2 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). LATS2 expression was examined in 73 NSCLC clinical specimens and 22 normal lung tissues using immunohistochemistry. Low levels of LATS2 protein were inversely associated with the T classification (P = 0.001), N classification (P = 0.005) and clinical stage (P = 0.001) in NSCLC patients. Patients with lower LATS2 expression had a significantly shorter overall survival than patients with high LATS2 expression. Multivariate analysis suggested that low expression of LATS2 was an independent prognostic indicator (P = 0.002) for the survival of patients with NSCLC. Furthermore, overexpression of LATS2 resulted in mobility inhibition in NSCLC cell lines A549 and H1299, and reduced protein level of matrix metalloproteinase-2 (MMP-2) and MMP-9. On the contrary, LATS2 siRNA treatment enhanced cell mobility and increased MMP-2 and MMP-9 protein expression level. In conclusion, low expression of LATS2 is a potential unfavorable prognostic factor and promoted cell invasion and migration in NSCLC.     

BCL2L12: A promising molecular prognostic biomarker in breast cancer

ObjectivesBCL2-like 12 (BCL2L12) is a new member of the BCL2 gene family that was discovered and cloned by members of our group and found to be expressed in the mammary gland. Many genes of the BCL2 family were found to be implicated in breast carcinogenesis and to serve as possible prognostic markers. The aim of the present study was the quantification of BCL2L12 mRNA expression in order to assess its value as a prognostic tissue biomarker in breast cancer (BC).Design and methodsBCL2L12 mRNA levels were determined in a statistically significant sample size of cancerous (N = 108) and adjacent non-cancerous (N = 71) breast tissues using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Relative quantification analysis was conducted using the comparative C_T (2^− ΔΔC_T) method, whereas the association between BCL2L12 expression and clinopathological data, disease-free survival (DFS) and overall survival (OS) were estimated by statistical analysis.ResultsBCL2L12 mRNA expression was decreased in malignant samples compared to the histologically normal counterparts (p = 0.012). Significant relationships between BCL2L12 expression and TNM stages (p = 0.009), metastatic potential (p = 0.012), tumor size (p = 0.04) and age (p = 0.024) were observed. Moreover, Kaplan–Meier and Cox univariate analyses indicated that BCL2L12 expression is associated with longer DFS, whereas multivariate analysis pointed out the independent favorable prognostic value of BCL2L12.ConclusionsAccording to our results, BCL2L12 mRNA expression is a favorable prognostic marker of DFS for BC patients, suggesting its possible application as a novel prognostic indicator of this malignancy.     

Cancer-Related Symptom Clusters,Eosinophils, and Survival in Hepatobiliary Cancer: An Exploratory Study

ContextThe study of symptom clusters is gaining increased attention in the field of oncology in an attempt to improve the quality of life of patients diagnosed with cancer.ObjectivesThe aims of the present study were to 1) determine the prevalence and distribution of pain, fatigue, and symptoms of depression and their covariation as a cluster in people with hepatobiliary carcinoma (HBC), 2) characterize how variation in each individual symptom and/or their covariation as a cluster are associated with changes in immunity, and 3) determine if the symptom clusters, and associated biomarkers, are related to survival in people diagnosed with HBC.MethodsTwo hundred six participants diagnosed with HBC completed a battery of standardized questionnaires measuring cancer-related symptoms. Peripheral blood leukocytes were measured at diagnosis and at three- and six-month follow-ups. Survival was measured from the date of diagnosis to death.ResultsCancer-related symptoms were prevalent and two-step hierarchical cluster analyses yielded three symptom clusters. High levels of pain, fatigue, and depression were found to be associated with elevated eosinophil percentages (F[1,78] = 3.1, P = 0.05) at three- and six-month follow-up using repeated-measures analysis of variance. Using multivariate latent growth curve modeling, pain was the primary symptom associated with elevated eosinophil percentages between diagnosis and six months (z = 2.24, P = 0.05). Using Cox regression, vascular invasion and age were negatively associated with survival (Chi-square = 21.6, P = 0.03). While stratifying for vascular invasion, Kaplan-Meier survival analysis was performed, and eosinophil levels above the median for the sample were found to be related to increased survival in patients with and without vascular invasion (Breslow Chi-square = 4.9, P = 0.03). Symptom clusters did not mediate the relationship between eosinophils and survival.ConclusionCancer-related symptoms, particularly pain and depression, were associated with increased percentages of eosinophils. The presence of symptoms may reflect tumor cell death and be indicative of response to treatment, or other processes, in patients with HBC.     

Characteristics and Outcomes of Patients Admitted to the Acute Palliative Care Unit From the Emergency Center

ContextMost patients admitted to acute palliative care units (APCUs) are transferred from inpatient oncology units. We hypothesized that patients admitted to APCUs from emergency centers (ECs) have symptom burdens and outcomes that differ from those of transferred inpatients.ObjectivesThe purpose of this retrospective cohort study was to compare the symptom burdens and survival rate of patients admitted to an APCU from an EC with those of inpatients transferred to the APCU.MethodsAmong the 2568 patients admitted to our APCU between September 1, 2003 and August 31, 2008, 312 (12%) were EC patients. We randomly selected 300 inpatients transferred to the APCU as controls (The outcome data were unavailable for two patients). We retrieved data on patient demographics, cancer diagnosis, Edmonton Symptom Assessment System scores, discharge outcomes, and overall survival from time of admission to the APCU.ResultsThe EC patients had higher rates of pain, fatigue, nausea, and insomnia and were less likely to be delirious. They were more than twice as likely to be discharged alive than transferred inpatients. Kaplan-Meier plot tests for product-limit survival estimate from admission to APCU for EC patients and inpatients were statistically significant (median survival 34 vs. 31 days, P < 0.0001). In multivariate analysis, EC admission (odds ratio [OR] = 1.8593, 95% confidence interval [CI] 1.1532–2.9961), dyspnea (OR = 0.8533, 95% CI 0.7892–0.9211), well-being (OR = 1.1192, 95% CI 1.0234–1.2257), and delirium (OR = 0.3942, 95% CI 0.2443–0.6351) were independently associated with being discharged alive.ConclusionThe EC patients have a higher acute symptom burden and are more likely to be discharged alive than transferred inpatients. The APCU was successful at managing symptoms and facilitating the discharge of both inpatients and EC patients to the community although the patients had severe symptoms on admission.     

Expression of STK15 mRNA in hepatocellular carcinoma and its prognostic significance

ObjectivesTo investigate whether the STK15 mRNA expression correlates with clinicopathologic features and the prognosis of HCC patients.Design and methodsThree hepatoma cell lines, two normal liver epithelial cell lines, hepatoma tissues, adjacent tumor tissues and normal liver tissues were obtained from 46 HCC patients. Semi-quantitative RT-PCR assays were performed to detect the expression of STK15 mRNA in above cell lines and tissues. Moreover, the expression of STK15 protein in hepatoma tissues, adjacent tumor tissues and normal liver tissues was also examined by immunohistochemical staining. Finally, correlations between STK15 mRNA expression and the clinicopathological features and prognosis of HCC patients were evaluated.ResultsSTK15 mRNA showed higher levels in hepatoma cell lines than in normal liver epithelial cell lines. Moreover, the mean levels of STK15 mRNA and protein expression showed statistical difference between tumor tissues, tumor adjacent tissues and normal liver tissues (P < 0.01). By immunohistochemical analysis, we found that paraffin-embedded archival HCC tissues showed higher expression of STK15 than adjacent tumors and normal liver tissues. Furthermore, HCC patients with higher STK15 mRNA expression showed poorer prognosis than those with lower STK15 mRNA expression. The high level of STK15 mRNA expression was significantly correlated with tumor stage (P = 0.0081), more frequent lymph node (P = 0.0380) or hematogenous metastasis (P = 0.0066), and a higher incidence of cancer-related death (P = 0.0083). Furthermore, the disease-free survival (DFS) and overall survival (OS) rates of HCC patients with higher STK15 mRNA expression group (47.6% and 52.7%) were significantly lower than those of patients with low STK15 mRNA expression group (56.9% and 68.8%, P = 0.0018 and 0.0047).ConclusionsSTK15 mRNA might be a good marker for predicting the prognosis of HCC patients.     

The expression of TSSC3 and its prognostic value in patients with osteosarcoma

Osteosarcoma is one of the most common primary bone tumors in children and adolescents, typically presenting with poor prognosis. Recent studies have found that TSSC3 had a potential capability in suppressing the tumor development in osteosarcoma. Our purpose was to explore the role of TSSC3 in the clinical outcome of osteosarcoma patients. Firstly, we detected the expression of TSSC3 at mRNA level by quantitative real-time polymerase chain reaction (qRT-PCR). The result demonstrated that TSSC3 expression was lower in osteosarcoma patients than in healthy controls (P < 0.05). Then, the relationship between TSSC3 and clinicopathological characteristics was analyzed by chi-square test which manifested that WHO grade, metastasis, and recurrence were vital influential factors on the expression of TSSC3 (P < 0.05). We also estimated the association between TSSC3 and overall survival of osteosarcoma patients by Kaplan–Meier analysis as well as assessed the prognostic value of TSSC3 and clinicopathological characteristics through cox regression analysis. Patients with high TSSC3 expression were proved to live longer than those with low TSSC3 expression (log rank test, P < 0.05). TSSC3 expression (P = 0.032, HR = 0.405, 95%CI = 0.177–0.926) and metastasis (P = 0.010, HR = 2.849, 95%CI = 1.291–6.287) were considered to be independent prognostic factors in osteosarcoma. Taken together, our findings provided preliminary evidence that the TSSC3 was a prognostic marker in osteosarcoma and this might be useful for the therapy of osteosarcoma.     

Prognostic Factors of Survival in Patients With Advanced Cancer Admitted to Home Care

ContextData regarding prognostication of life expectancy in patients with advanced cancer are of paramount importance to patients, families, and clinicians. However, data regarding patients followed at home are lacking.ObjectivesThe aim of this study was to evaluate the correlation between various factors recorded at the beginning of home care assistance and survival.MethodsA sample of consecutive patients admitted to two home care programs was surveyed. A preliminary consensus was achieved as to the possible variables easy to be recorded at home. These included age at the time of home care admission, gender, residence, marital status, primary cancer diagnosis, Karnofsky Performance Status (KPS) score, measures of systolic blood pressure and heart rate, cyanosis, use of oxygen, and body temperature. The Edmonton Symptom Assessment System was used to record the intensity of each symptom. Patients were divided into two groups: patients with a survival of less than 10 days (short survival) and patients with a survival of 10 days or more (medium-long survival).ResultsThree hundred seventy-four consecutive patients admitted to home care programs were surveyed, of which 187 were male. The mean ± SD age was 72.1 ± 12.7 years. The mean survival was 56.2 ± 65 days. Mean survival was 71.5 ± 67 days (287 patients) and 5.6 ± 2.7 days (87 patients) in the short and medium-long survival groups, respectively. No association between type of tumor and survival was observed (P = 0.162). Univariate logistic regression analysis revealed that male gender (P = 0.020), older age (P = 0.012), lower KPS scores (P < 0.0005), systolic blood pressure less than 100 mm Hg (P = 0.003), heart rate greater than 100 beats per minute (P = 0.0006), delirium (P = 0.004), the use of oxygen (P = 0.002), intensity of fatigue (P = 0.006), drowsiness (P < 0.0005), anorexia (P < 0.0005), dyspnea (P < 0.0005), poor sense of well-being (P < 0.0005), and distress score (P < 0.0005) were associated with a survival of less than 10 days. Marital status, residence, cognitive function, fever, pain, depression, and anxiety were not found to be significantly correlated with survival. In a multiple logistic regression model, low systolic blood pressure and high heart rate, gender, delirium, use of oxygen, KPS score, drowsiness, anorexia, and dyspnea were significantly correlated with a shorter survival.ConclusionLow systolic blood pressure and high heart rate, male gender, poor KPS score, anorexia, and dyspnea were correlated with a shorter survival. Moreover, patients with low systolic blood pressure and high heart rate, male gender, poor KPS score, and greater intensity of anorexia and dyspnea are more likely to die within one week. The combination of physical symptoms from the Edmonton Symptom Assessment System and other parameters included in this study, which are simple to assess and are repeatable at home, should be further explored in future studies to provide a simple tool for use with patients with advanced cancer admitted to a home care program.     

Serum neural precursor cell-expressed,developmentally down regulated 9 (NEDD9) level may have a prognostic role in patients with gastric cancer

BackgroundNeural precursor cell-expressed, developmentally down regulated 9 (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved in cancer cell adhesion, migration and invasion. The prognostic value of NEDD9 has been evaluated before and its expression is a predictor of poor prognosis in cancer patients. The objective of this study was to determine the clinical significance of the serum levels of NEDD9 in gastric cancer (GC) patients.Patients and methodsA total of 68 patients with a pathologically confirmed diagnosis of GC were enrolled into this study. Serum NEDD9 concentrations were determined by the solid-phase sandwich (ELISA) method. Twenty-eight healthy age- and sex-matched controls were included into the analysis.ResultsThe median age at diagnosis was 60 years, range 21 to 84 years. Forty-nine (72%) patients were male and cardia was the most common tumor localization (n = 37, 77%) in GC patients. The most frequent histologic subtype was adenocarcinoma (n = 45, 66%). Liver was the most common metastatic site in 32 patients with metastasis (n = 14, 44%). Sixty-one percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. The median follow-up time was 8 months (range 1 to 23 months). At the end of the observation period, 17 patients (25%) experienced disease progression and 28 of the remaining patients (41%) died. Median progression-free survival (PFS) and overall survival (OS) of the whole group were 4.0 ± 0.7 months [95% confidence interval (CI) = 3–5 months] and 14.6 ± 1.2 months (95% CI = 12–17 months), respectively. One-year and 2-year OS rates were 54.4% (95% CI = 41.3–67.5) and 51.2% (95% CI = 37.3–65.1), respectively. The median serum NEDD9 levels of GC patients were significantly higher than controls (1339.51 vs. 1187.91 pg/mL, P = 0.02). There was no significant difference according to known disease-related clinicopathological or laboratory parameters (P > 0.05). Serum NEDD9 levels had a significant impact on PFS (P = 0.04). On the other hand, serum NEDD9 levels showed no significantly adverse effect on OS (P = 0.50).ConclusionSerum NEDD9 level may be a diagnostic marker for GC patients. Moreover, our study results showed that it was elevated in GC patients and had an unfavorable prognostic effect. However, it has no predictive role on CTx response.     

Associations Among Hypogonadism,C-Reactive Protein,Symptom Burden,and Survival in Male Cancer Patients with Cachexia: A Preliminary Report

ContextCachexia is characterized by muscle wasting, anorexia, and elevated inflammatory markers. In patients without cancer, hypogonadism is associated with lower lean body mass, increased symptom burden, and decreased survival. Hypogonadism in cancer cachexia could exacerbate symptoms, facilitate a proinflammatory state, and decrease survival.ObjectivesTo explore the relationships among these factors, a retrospective study of male cancer patients was conducted.MethodsThe charts of 98 consecutive male patients referred to a cachexia clinic at a comprehensive cancer center were reviewed. All patients reported weight loss of >5% within the preceding six months; the median age was 60 years. Fifty-seven (58%) had serum C-reactive protein (CRP), and 68 (69%) had total testosterone evaluated. Symptoms were evaluated by the Edmonton Symptom Assessment Scale.ResultsMedian CRP was 20 mg/L, and median testosterone level was 185 ng/dL (6.42 nmol/L) (normal ≥240 ng/dL or 8.36 nmol/L). There was an inverse correlation between testosterone and CRP levels (P < 0.01). Lower testosterone was associated with increased dyspnea and insomnia (P < 0.05). Poor appetite and insomnia (P < 0.05) correlated with elevated CRP. Survival of patients with testosterone levels ≤185 ng/dL (6.42 nmol/L) was decreased compared with that of those with levels >185 ng/dL (13 vs. 62 weeks, P = 0.004). Patients with CRP levels >10 mg/L had decreased survival compared with those with levels ≤10 mg/L (15 vs. 46 weeks, P = 0.01). The combination of hypogonadism and elevated CRP was associated with poorer prognosis. Elevated CRP levels were associated with increased symptom burden and decreased survival. Low testosterone was associated with decreased survival and correlated inversely with CRP levels, dyspnea, and insomnia.ConclusionOur preliminary results suggest that testosterone and CRP may be additive or synergistic as markers for survival in male patients and could be useful in future prognostic models.     

Traditional Chinese Medicine treatment as maintenance therapy in advanced non-small-cell lung cancer: A randomized controlled trial

ObjectivesMaintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) is an increasingly hot topic in the field of clinical NSCLC research. This study aimed to evaluate the effects of Traditional Chinese Medicine (TCM) treatment as maintenance therapy on time to progression (TTP), quality of life (QOL), overall survival (OS) and 1-year survival rate in patients with advanced NSCLC.MethodsThis study was conducted as a randomized, controlled, open-label trial. 64 non-progressive patients who responded to initial therapy were randomized 1:1 to the TCM arm (treated with herbal injection (Cinobufacini, 20 ml/d, d1–d10), herbal decoction (d1–d21) and Chinese acupoint application (d1–d21), n = 32) or to the chemotherapy arm (treated with pemetrexed (non-squamous NSCLC, 500 mg/m², d1), docetaxel (75 mg/m², d1) or gemcitabine (1250 mg/m², d1 and d8), n = 32). Each therapy cycle was 21 days. They were repeated until disease progression, unacceptable toxicity, or until the patients requested therapy discontinuation. The primary end point was TTP; the secondary end points were QOL, OS and 1-year survival rate. “Intention-to-treat” analysis included all randomized participants.ResultsTCM treatment prolonged median TTP for 0.7 months compared with chemotherapy, but it was not statistically significant (3.0 months vs. 2.3 months, P = 0.114). Median OS time for TCM treatment did not offer a significant advantage over for chemotherapy (21.5 months vs. 18.8 months, P = 0.601). 1-year survival rate of TCM treatment significantly improved than that of chemotherapy (78.1% vs. 53.1%, P = 0.035). TCM treatment can significantly improve QOL when compared to chemotherapy as assessed by EORTC QLQ-C30 and EORTC QLQ-LC13 QOL instruments.ConclusionsTCM maintenance treatment had similar effects on TTP and OS compared with maintenance chemotherapy, but it improved patients' QOL and had higher 1-year survival rate. TCM Maintenance treatment is a promising option for advanced NSCLC patients without progression following first-line chemotherapy.