Abstract
As there are millions of cancer deaths every year, it is of great value to identify applicable prognostic biomarkers. As an important alarm, the prognostic role of high mobility group box 1 (HMGB1) in cancer remains controversial. We aim to assess the association of HMGB1 expression with prognosis in cancer patients. Systematic literature searches of PubMed, Embase and Web of Science databases were performed for eligible studies of HMGB1 as prognostic factor in cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the influence of HMGB1 expression on overall survival (OS) and progression-free survival (PFS) in cancer patients. 18 studies involving 11 different tumor types were included in meta-analysis. HMGB1 overexpression was significantly associated with poorer OS (HR: 1.99; 95% CI, 1.71-2.31) and PFS (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamous-cell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma. Subgroup analyses indicated geographical area and size of studies did not affect the prognostic effects of HMGB1 for OS. Morever, HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse-transcription polymerase chain reaction in tissues. HMGB1 overexpression is associated with poorer prognosis in patients with various types of cancer, suggesting that it is a prognostic factor and potential biomarker for survival in cancer.
Highlights
According to the reports from WHO, there were 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer in 2012 worldwide [1]
high mobility group box 1 (HMGB1) overexpression was significantly associated with poorer overall survival (OS) (HR: 1.99; 95% confidence intervals (CIs), 1.71-2.31) and progression-free survival (PFS) (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamouscell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma
HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse-transcription polymerase chain reaction in tissues
Summary
According to the reports from WHO, there were 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer (within 5 years of diagnosis) in 2012 worldwide [1]. Combination of surgery, radiotherapy and chemotherapy remains the standard treatment in most cancer cases, not all patients derive benefit from it [2]. We have known that HMGB1 was involved in transcription regulation of many cancer genes, including E-selectin, TNF-α, BRCA1 and insulin receptor [6,7,8,9]. In addition to these reports, recent evidence demonstrates that HMGB1 plays an important role in the tumorigenesis and progression of many types of cancers such as digestive system, urogenital system, skin, bone, and blood cancer [10,11,12]. We performed a literature-based systematic review and meta-analysis in order to assess the association of HMGB1 expression with prognosis in patients with cancer
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