Expression of heme oxygenase-1 in non-small cell lung cancer (NSCLC) and its correlation with clinical data

Degese, María Sol; Mendizábal, Javier Enrique; Gandini, Norberto Ariel; Gutkind, J. Silvio; Molinolo, Alfredo A.; Hewitt, Stephen M.; Curino, Alejandro Carlos; Coso, Omar A.; Facchinetti, María Marta

doi:10.1016/j.lungcan.2012.02.016

Cited by 77 publications

(67 citation statements)

References 36 publications

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“…In addition to numerous physiological functions, HO-1 has important roles in various pathological conditions, including certain types of cancer. Increased expression levels of HO-1 were previously demonstrated to be associated with malignant potential, cancer cell dissemination and poor prognosis in renal cell, lung and gastric carcinomas (14,25,26). However, other studies have indicated that increased HO-1 expression levels are associated with favorable outcomes in colorectal (27) and tongue cancers (28).…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

“…Notably, HO-1 expression levels are elevated in various types of cancer (12)(13)(14) and have been demonstrated to regulate certain cancer-associated molecules (15,16). A previous study reported that HO-1 expression levels are significantly associated with malignant aggressiveness and prognosis in patients with bladder cancer (17).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Many examples suggest that HO-1 abundance and localization are associated with tumor formation (20,31). In nonsmall lung cells, cancer patients with a high HO-1 expression ratio in tumor tissue compared with normal tissue had a significantly poorer prognosis and a higher metastatic rate compared with those with a low HO-1 expression ratio (20). In vitro, the invasive and migratory abilities of A549 and H441 lung cancer cells significantly increased after high (20-fold increase) exogenous HO-1 over-expression and significantly decreased after HO-1 silencing.…”

Section: Maladaptive Consequences Of Ho-1 Overexpression and Cellularmentioning

confidence: 99%

Heme Oxygenase in Neonatal Lung Injury and Repair

Dennery

2014

Antioxidants & Redox Signaling

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Significance: Premature and sick neonates are often exposed to high concentrations of oxygen, which results in lung injury and long-term adverse consequences. Nevertheless, neonates are more tolerant to hyperoxia than are adults. This may be, in part, explained by the high lung content of heme oxygenase-1 (HO-1), the rate-limiting enzyme in the degradation of heme and an important stress protein. The abundance of HO-1 dictates its cytoprotective and deleterious effects. Interestingly, in response to hyperoxia, lung HO-1 mRNA is not further up-regulated in neonates, suggesting that lung HO-1 gene expression is tightly regulated so as to optimize cytoprotection when faced with an oxidative stress such as hyperoxia. Recent Advances: In addition to the lack of induction of HO-1 mRNA, neonatal lung HO-1 protein is observed in the nucleus in neonatal mice exposed to hyperoxia but not in adults, which is further evidence for the developmental regulation of HO-1. Nuclear HO-1 had unique properties independent of its enzymatic activity. In addition, there has been increasing evidence that nuclear HO-1 contributes to cellular proliferation and malignant transformation in several human cancers. Critical Issues: Since HO-1 has dual effects in cytoprotection and cellular proliferation, the titration of HO-1 effects is critical to ensure beneficial actions against oxidative stress. Future Directions: Much more has to be understood about the specific roles of HO-1 so as to manipulate its abundance and/or nuclear migration to maximize the therapeutic benefit of this pleiotropic protein in the neonatal lung.

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“…However, the advantages in anti-apoptotic and cytoprotective roles of HO-1 turn out to induce tumor-progression in cancer chemotherapeutic [5]. It was reported that increased expression of HO-1 in human malignant cancer tissue was observed, such as lung cancers [6]. One of reports showed that high expression of HO-1 was associated with poor prognosis in lung cancer [7].…”

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confidence: 99%

MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1

Gao¹,

Peng²,

Peng³

2014

neo

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Clear-cell renal cell carcinoma is a highly treatment-resistant tumor type. Heme oxygenase-1 plays an anti-apoptotic role in cancer chemotherapeutic inducing tumor-progression. The miR-200 family was involved in the process of mesenchymal-epithelial transition (MET) during renal development. In the present study, we demonstrated the regulatory relationship between miR-200c and HO-1. We provided evidences to elucidate that miR-200c could sensitize ccRCC cells to sorafenib or imatinib to inhibit cell proliferation, at least partly by targeting HO-1. Moreover, the correlation between miR-200c and HO-1 expression level and drug resistance in ccRCC was also determined. Combined application with chemotherapeutic drugs, miR-200c, a HO-1 inhibitor, may enhance the efficiency of therapy by promoting both apoptosis and autophagy.

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Expression of heme oxygenase-1 in non-small cell lung cancer (NSCLC) and its correlation with clinical data

Cited by 77 publications

References 36 publications

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

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

Heme Oxygenase in Neonatal Lung Injury and Repair

MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1

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