Consistent with this hypothesis, large tumors ( ?5?cm in diameter) were present more frequently in patients with anti-eEF2 autoantibodies compared with those with small tumors (Li et al. significantly higher in subjects with a positive history of alcoholism (test and ANOVA followed by LSD assessments were used for comparisons between groups. Pearson correlation was used to assess linear correlations between log-anti-HSP27 and continuous variables and multiple linear regression analysis to evaluate their RAF1 impartial association with log-anti-HSP27. Logistic regression analysis was performed to establish if log-anti-HSP27 values were associated with HCC with respect to other non-malignant chronic liver disease, independently of age, FP, DCP, and s-HSP27. A 2-tailed value of ?0.05 was considered statistically significant. Analyses were performed using the SPSS software (version 25). Results Patient characteristics The clinical characteristics of the patients included in the study are shown in Table ?Table1.1. Patients with HCC, cirrhosis, and CAH were comparable for age and gender. Healthy control subjects had similar age and percentage of male (age 65.2 (7.3) years, male 69.0%). Etiology was predominantly viral and hepatitis C was the most frequent cause of chronic liver disease. Most of the patients with liver cirrhosis were in Child-Pugh class A and only a minority was in class C. Most patients with HCC experienced an early tumor and 73% experienced a single nodule. Values of FP, DCP, sHSP27 were, as expected, higher in patients with HCC. Table 1 Characteristics of the patients recruited in the study valuehepatocellular carcinoma, chronic active hepatitis, -fetoprotein, des-gamma carboxy prothrombin; serum warmth shock protein 27 Anti-HSP27 levels Anti-HSP27 levels were measurable in all subjects with a right-skewed distribution of values. Anti-HSP27 antibody levels did not differ significantly among groups as depicted in Fig.?1. Table ?Table22 shows anti-HSP27 values by categorical variables in patients with chronic liver disease (HCC, CAH, and cirrhosis). Anti-HSP27 levels did not differ by sex and Child-Pugh class. However, in patients with CAH/cirrhosis, anti-HSP27 levels were significantly higher EO 1428 in subjects with a positive history of alcoholism. Moreover, in the whole group (HCC + CAH + liver cirrhosis), anti-HSP27 levels were significantly higher in alcohol-positive than in alcohol-negative patients (47.0 (27.4C50.8) vs. 31.5 (17.6C50.6), valueCirrhosis and CAH (valueSex??Women29.8 (15.3C53.9)0.66131.7 (17.1C41.8)0.131??Men36.2 (19.7C52.1)35.2 (20.8C56.3)Alcohol-related etiology??No32.2 (15.3C52.7)0.16331.3 (19.3C48.0)0.003??Yes38.6 (28.3C48.9)53.4 (33.3C71.8)Child-Pugh??A34.0 (23.1C52.1)0.22633.2 (20.6C59.3)0.497??B29.8 (13.9C53.9)34.1 (23.7C43.9)Tumor stage??I29.8 (26.6C52.7)0.938-??II34.0 (15.0C52.9)-??III33.3 (25.6C43.1)-??IV40.0 (31.6C48.8)-Nodule number??131.4 (18.9C52.9)0.873C?? 137.6 (22.0C44.5)CNodule size?2?cm29.0 (22.8C54.0)0.744- ?2?cm35.9 (18.9C37.1)- Open in a separate window Data are expressed as median (25th, 75th percentile) hepatocellular carcinoma, chronic active hepatitis Univariate and multivariate regression Univariate analysis showed that log-anti-HSP27 levels were not linearly correlated with log-sHSP27 ( em r /em ?=???0.004, em p /em ?=?0.958). Moreover, there was no significant correlation between log-anti-HSP27 and both log-DCP ( em r /em ?=?0.129, em p /em ?=?0.114) and log-FP (all groups: em r /em ?=?0.03, em p /em ?=?0.715; HCC: em r /em ?=?0.051, em p /em ?=?0.674; CAH: em r /em ?=?0.111, em p /em ?=?0.633; CIR: em r /em ?=???0.006, em p /em ?=?0.962). The only continuous variable significantly associated with anti-HSP27 was the level EO 1428 of hemoglobin (Hb) ( em r /em ?=?0.193 em p /em ?=?0.035) in patients with chronic liver disease. In stepwise multivariate analyses, log-anti-HSP27 was significantly associated with age ( em /em ?=?0.283 em p /em ?=?0.001), Hb ( em /em ?=?0.218, em p /em ?=?0.012), and alcohol-related etiology ( em /em ?=?0.388, em p /em ?=?0.000), while the other included variables (sex, log-sHSP27) were not retained in the final model that explained 18% of log-anti-HSP27 variability. Logistic regression analysis In logistic regression analysis performed in all patients with chronic liver disease with and without HCC ( em n /em ?=?151), log-antiHSP27 was not associated with the likelihood of having HCC with respect to other chronic liver diseases in a model including age, sex, Hb, FP, and DCP. As expected, both FP and DCP markedly increased the OR of having HCC (FP: OR 4.3 (95% CI 1.8C10.0); DCP OR 13.2 (95% CI 3.4C50.6)). Conversation We have previously reported that serum levels of HSP27 are an independent biomarker of HCC in patients with chronic liver disease EO 1428 (Gruden et al. 2013). In contrast, in the present study, performed on the same study base, we found that anti-HSP27 values were similar in patients with HCC, CAH, liver cirrhosis, and healthy control subjects. Moreover, in logistic regression analysis, anti-HSP27 levels were not associated with an increased OR of having HCC. Therefore, this cross-sectional study demonstrates that anti-HSP27 antibodies are not a candidate biomarker for early HCC. At variance with our results, levels of anti-HSP27 were enhanced in women with ovarian carcinoma and breast cancer compared with those of the control subjects (Conroy et al. 1998; Olejek et al. 2009; Homaei-Shandiz et al. 2016). This shows that the relevance of anti-HSP antibody amounts as tumor biomarker could be related to the precise cancer type. Anti-HSP27 amounts didn’t differ by HCC significantly.
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