Two-tailed P-values <0.05 were considered statistically significant. 24 We also performed the sensitivity analysis by sequentially omitting each individual study to validate the stability of the synthetic results. 23 Publication bias was statistically assessed via the Egger’s test and visually evaluated by funnel plots. 22 Taking into account the relatively small meta-analysis, the random-effects model was always applied to provide better estimates with wider CIs. Significant heterogeneity among studies was defined as I 2>50%. Heterogeneity was measured using the Higgins I 2 test. In addition, the pooled odds ratio (OR) and 95% CI were used to evaluate the correlation between HSF1 expression and the clinicopathological parameters of solid tumors.
The overall HR >1 that failed to overlap its 95% CI indicated a poor prognosis in patients with HSF1 overexpression. The combined HR and 95% CI were calculated to assess the association between HSF1 expression and OS of solid tumor patients. Stata 12.0 (StataCorp LP, College Station, TX, USA) and RevMan software 5.3 (The Cochrane Collaboration, Oxford, UK) were used to conduct all the statistical analyses. The aim of the present meta-analysis is to make a comprehensive analysis on potential prognostic and clinicopathological roles of HSF1 in solid tumors. 18, 19 Nevertheless, the results of these individual studies are not consistent and conclusive because of the small sample size. 17 Furthermore, evidence implies that the elevation of HSF1 expression is correlated with poor survival of tumor patients. Growing studies have demonstrated that HSF1 is overexpressed in a series of solid tumors such as esophageal squamous cell carcinoma (ESCC), 8, 9 breast cancer (BC), 10, 11 hepatocellular carcinoma (HCC), 12 – 14 osteosarcoma, 15 non-small-cell lung cancer (NSCLC), 16 and pancreatic cancer. Identification of many prognostic factors in recent years has helped more accurate prognostic prediction of tumor patients. In tumor cells, however, this feedback inhibition may be ineffective. Simultaneously, HSF1 activation is repressed by interaction with HSP overexpression in nontumor cells. 4, 5 HSPs such as HSP27, HSP70, and HSP90 are important molecular chaperones that promote proper folding, transportation, and degradation of proteins within cells. 3 However, in the event of proteotoxic stress, this inactive monomeric HSF1 forms a phosphorylated trimer and then triggers the transcription of heat shock proteins (HSPs) by binding to consensus heat shock elements (HSE). HSF1 exists primarily as an inactive monomer located in the cytoplasm and is dispensable for cellular viability under normal proteome homeostasis conditions. HSF1 is the master regulator of proteotoxic stress response that protects cells against heat, inflammation, ischemia, and other noxious conditions.
1, 2 Therefore, there is an urgent need to seek reliable and feasible tumor biomarkers to assist in obtaining additional prognostic information. Despite the improvements in diagnostic methods and treatment techniques, the 5-year survival rate for all tumors is not optimistic, especially in developing countries.
Cancer remains a growing public health problem worldwide due to the increasing tendency of overall morbidity over the past decades.