title: Quantitative measurement of iNOS expression in melanoma, nasopharyngeal, colorectal, and breast tumors of Tunisian patients: comparative study and clinical significance.
abstract: Chronic inflammation increases the risk of development of human malignancies. iNOS is an enzyme dominantly expressed during inflammatory reactions and seems to play a critical role in tumorigenesis. Our aim was to assess the iNOS expression in four types of human tumors: breast, colorectal, nasopharyngeal, and melanoma, of Tunisian patients. The level of iNOS was measured by RT-QPCR in tumor specimens. We showed that the expression of iNOS was higher in breast compared to colorectal and nasopharyngeal tumors, whereas in melanoma, the level of iNOS expression was low. Significant associations were found when comparing the iNOS expression in cancers pairs such as melanoma versus colorectal (p < 0.0001), colorectal versus nasopharyngeal (p = 0.0072), and melanoma versus breast (p < 0.0001). Furthermore, iNOS expression correlated with the Breslow thickness, Clark level, and histological subtype in melanoma, while in nasopharyngeal carcinoma, significant association was seen with age at diagnosis, TNM, metastasis, response to treatment, and expression of COX-2. Furthermore, the expression of iNOS correlated with tumor size, TNM, tumor location, and histological type in colorectal cancer, and with tumor size, tumor stage, SBR grade, and triple negative cases in breast cancer. On the other hand, immunohistochemistry analysis shows that the expression of iNOS is observed in the stroma and tumor cells as well. Overall, our results highlight that iNOS is a reliable marker for advanced stage and aggressive behavior for the four types of cancer and might be a potential promising therapeutic target.
authors.affiliation: Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP"K"1177, Sfax, 3018, Tunisia.|Inserm U1016, CNRS UMR8104, Institut Cochin and University Paris Descartes, 75014, Paris, France.|Inserm U1173 and University of Versailles Saint-Quentin, 78180, Montigny-le-Bretonneux, France.
authors.forename: Emna
authors.initials: E
authors.lastname: Dabbeche-Bouricha
authors.affiliation: Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP"K"1177, Sfax, 3018, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Hadiji-Abbes
authors.affiliation: Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP"K"1177, Sfax, 3018, Tunisia.
authors.forename: Rania
authors.initials: R
authors.lastname: Abdelmaksoud-Damak
authors.affiliation: Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP"K"1177, Sfax, 3018, Tunisia.
authors.forename: Nesrine
authors.initials: N
authors.lastname: Alaya
authors.affiliation: Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP"K"1177, Sfax, 3018, Tunisia.
authors.forename: Wajdi
authors.initials: W
authors.lastname: Ayadi
authors.affiliation: Department of Anatomo-pathology, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, 3000, Tunisia.
authors.forename: Slim
authors.initials: S
authors.lastname: Charfi
authors.affiliation: Department of Anatomo-pathology, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, 3000, Tunisia.
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.affiliation: Department of Anatomo-pathology, Centre Hospitalo-Universitaire Habib Bourguiba, Sfax, 3000, Tunisia.
authors.forename: Tahia
authors.initials: T
authors.lastname: Sellami-Boudawara
authors.affiliation: Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP"K"1177, Sfax, 3018, Tunisia. raja.gargouri@cbs.rnrt.tn.
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D014416:Tunisia / Q000453:epidemiology
chemical_list: C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Breast cancer; Colorectal cancer; Expression levels; Melanoma; Nasopharyngeal carcinoma; iNOS