Pathological significance and prognostic implications of heme oxygenase 1 expression in non-muscle-invasive bladder cancer: Correlation with cell proliferation, angiogenesis, lymphangiogenesis and expression of VEGFs and COX-2

Abstract

Abstract. Heme oxygenase 1 (HO-1) is a stress-response protein and its expression is associated with malignant potential and poor prognosis in several types of cancer. The present study investigated the association between HO-1 expression levels and the pathological features, clinical outcomes and other associated factors in patients with non-muscle-invasive bladder cancer (NMIBC). HO-1 expression was evaluated using immunohistochemistry in 147 formalin-fixed tissue specimens. The proliferation index, microvessel density, lymph vessel density and expression of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D were also investigated. Correlations among variables were analyzed by multivariate analysis. Survival was assessed using Kaplan-Meier survival curves and multivariate statistics. HO-1 expression levels in high-grade and pT1 tumors were significantly higher compared with low-grade and pTa tumors, and were correlated with the proliferation index (P<0.001), lymph vessel density (P=0.021) and COX-2 expression levels (P=0.003). The proliferation index and COX-2 expression levels were also identified as independent contributing factors in multivariate models. Kaplan-Meier survival curves associated HO-1 expression with a poor prognosis in metastasis-free (P=0.047) and cause-specific survival (P=0.017), but not with urinary tract recurrence (P=0.231). Furthermore, HO-1 expression was identified by multivariate analysis to be a significant predictor for cause-specific survival (hazard ratio, 4.08; 95% confidence interval, 1.06-15.66; P=0.004). HO-1 has an important role in the malignant aggressiveness of NMIBC and its expression is associated with cause-specific survival. HO-1-associated activities are regulated by cancer cell proliferation, lymphangiogenesis and COX-2. The results suggest that HO-1 may be a potential therapeutic target and a useful predictive prognostic factor in patients with NMIBC.

Screening the active compounds of Phellodendri Amurensis cortex for treating prostate cancer by high-throughput chinmedomics

“…Both Caspase-3 and Bcl-2 play an important role in signal transduction of cell apoptosis49. COX-2 is an inflammatory mediator involved in the process of cell proliferation, migration, and apoptosis5051. These results indicate that the effect of PAC treatment on prostate cancer is mainly achieved by adjusting the expression of PSA, AR, COX-2, Bcl-2, and caspase3, and by further inhibiting the inflammatory microenvironment in vivo , finally inhibiting prostate cancer cell proliferation and inducing prostate cancer cell apoptosis, offering further effective intervention in the growth of prostate cancer xenograft tumours.…”

Clinicopathological and prognostic significance of heme oxygenase‐1 expression in small intestinal adenocarcinomas

“…According to the previous studies of HO‐1 for the resected malignancies, clinicopathologic and prognostic significance of its high expression were variable (Table ). In bladder cancer, especially non‐muscle‐invasive type, high HO‐1 expression is correlated with higher grade and T category, more frequent lymphovascular invasion, and shorter overall survival of patients . Similar to bladder cancer, high HO‐1 expression is associated with advanced stage, frequent nodal involvement, high metastatic rate, and poor prognosis of patients with lung cancer .…”

“…Immunohistochemical findings of HO‐1 in various carcinomas comparing to normal adjacent epithelium have been reported using variable interpreting methods . In spite of different methods for interpreting the expression of HO‐1, consistent higher HO‐1 expression has been observed in cancer cells than that in normal epithelial cells . Interestingly, HO‐1 expression levels are quite different in normal epithelial cells depending on organs.…”

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] In spite of different methods for interpreting the expression of HO-1, consistent higher HO-1 expression has been observed in cancer cells than that in normal epithelial cells. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Interestingly, HO-1 expression levels are quite different in normal epithelial cells depending on organs. Squamous cells of head and neck, urothelial cells, and thyroid follicular cells are negative for HO-1, 6,12,14 whereas intestinal and gastric epithelial cells are positive for HO-1.…”

“…In addition, HO-1 is a novel therapeutic target in patients with inflammatory bowel disease. 3 In the literature, HO-1 is also highly expressed in various cancers, including squamous cell carcinoma of the oral cavity, 5 head and neck cancer, 6 colorectal cancer, 4,7-9 gastric cancer, 10 urinary bladder cancer, [11][12][13][14] prostate cancer, 15 thyroid cancer, 16 lung cancer, 17,18 and breast cancer. 19 Potential functions of HO-1 for formation, progression, metastasis, and prognosis of cancers have been recently implicated.…”