Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is an extremely malignant tumor arising from the epithelial cells of the second-order or more proximal bile ducts. The poor prognosis of this disease is mainly due to the insufficient understanding of the pathogenesis, lack of early diagnosis methods and limited treatment modalities. The investigations on molecular biomarkers of ICC may help the early diagnosis, prognostic estimation and treatment recommendations. The aim of this study was to investigated the expression of the pro-inflammatory factor, high mobility group protein 1 (HMGB1) in ICC tissue and its clinical significance as well as its relationship with tumor microangiogenesis.
Methods: The HMGB1 expressions and tumor microvascular density (MVD) counts (CD31 expressions) in surgical specimens of ICC tissue and tumor adjacent tissue from 65 ICC patients and 30 specimens of normal bile duct tissues were detected by immunohistochemical staining. The relations of HMGB1 expression and MVD count with the clinicopathologic factors of ICC patients and their correlation in ICC tissue were determined, and their influences on prognosis of ICC patients were also analyzed.
Results: Both HMGB1 expression and MVD count presented a significant decreasing order in ICC tissue, tumor adjacent tissue and normal bile duct tissue (all P<0.05). The HMGB1 expression was significantly associated with the degree of tumor differentiation, vascular invasion and lymph node metastasis (all P<0.05), while the MVD count was significantly associated with vascular invasion of the tumor (P<0.05); there was a significant positive correlation between HMGB1 expression and MVD count in ICC tissue (r=0.330, P=0.008). In the whole group of ICC patients, the postoperative 1-, 3- and 5-year survival rates of patients were 55.4%, 36.9% and 7.7%. The survival rate in patients with positive HMGB1 expression was significantly lower than that in patients with negative HMGB1 expression (χ2=6.278, P=0.012), and in those with high MVD count was significantly lower than that in cases with low MVD count (χ2=5.101, P=0.024); the survival rate in patients with characteristics of both positive HMGB1 expression and high MVD count was significantly lower than those with only one or none of the characteristics (all P<0.05).
Conclusion: The HMG1 expression is elevated in ICC tissue and is closely related to the invasion, metastasis and prognosis of ICC. The action mechanism may be probably associated with HMG1 inducing tumor microangiogenesis through various signaling pathways and then promoting growth and progression of the tumor. HMG1 can be potentially used as an indicator for prognostic assessment and decision-making, and also provides a new direction for the targeted drug development.