Athanasios Tampakis1, Benjamin Weixler1,2, Silvan Rast1, Ekaterini-Christina Tampaki3,4, Eleonora Cremonesi5, Venkatesh Kancherla5, Nadia Tosti1,5, Christoph Kettelhack1, Charlotte K Y Ng6, Tarik Delko1, Savas D Soysal1, Urs von Holzen7,8,9, Evangelos Felekouras10, Nikolaos Nikiteas4, Martin Bolli1, Luigi Tornillo5, Luigi Terracciano5, Serenella Eppenberger-Castori5, Giulio C Spagnoli11, Salvatore Piscuoglio5,12, Markus von Flüe1,12, Silvio Däster1, Raoul A Droeser1. 1. Clarunis, University Centre for Gastrointestinal and Liver Disorders, Department of Visceral Surgery, University Hospital of Basel, Basel, Switzerland. 2. Department of Surgery, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany. 3. National Organization for the Provision of Healthcare Services, Department of Planning and Monitoring of Medicines Dispencing, Medicines Division, Athens, Greece. 4. 2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko General Hospital, Athens, Greece. 5. Institute of Pathology, University Hospital Basel, Basel, Switzerland. 6. Department of Biomedical Research, University of Bern, Bern, Switzerland. 7. Indiana University School of Medicine South Bend, Goshen Center for Cancer Care, Goshen, IN, USA. 8. Harper Cancer Research Institute, South Bend, IN, USA. 9. School of Medicine, University of Basel, Basel, Switzerland. 10. 1st Department of Propedeutic Surgery, Athens University Medical School, Laiko General Hospital, Athens, Greece. 11. Istituto CNR "Translational Pharmacology", Rome, Italy. 12. Department of Biomedicine, Visceral Surgery Research Laboratory, Clarunis, Basel, Switzerland.
Abstract
BACKGROUND: Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. METHODS: A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset. RESULTS: Expression of nestin and CD34 was observed only in the tumor stroma. Patients displaying high expression of nestin and CD34 demonstrated higher rates of T1 and T2 tumors (p = .020), lower vascular invasion (p < .001) and improved 5-year overall survival (65%; 95% CI = 55-73 vs 45%; 95% CI = 37-53) after adjusting for clinicopathological characteristics (HR: 0.67; 95% CI = 0.46-0.96). A moderate to strong correlation (r = 0.37-0.78, p < .03) of nestin and CD34 was demonstrated for the following markers; HIF-1α, CD4, CD8, FOXP3, IRF1, GATA3, CCL2, CCL3, CXCL12 and CCL21. CONCLUSIONS: Combined expression of nestin and CD34 expression is associated with better overall survival possibly by modulating a favorable immune response.
BACKGROUND: Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. METHODS: A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset. RESULTS: Expression of nestin and CD34 was observed only in the tumor stroma. Patients displaying high expression of nestin and CD34 demonstrated higher rates of T1 and T2 tumors (p = .020), lower vascular invasion (p < .001) and improved 5-year overall survival (65%; 95% CI = 55-73 vs 45%; 95% CI = 37-53) after adjusting for clinicopathological characteristics (HR: 0.67; 95% CI = 0.46-0.96). A moderate to strong correlation (r = 0.37-0.78, p < .03) of nestin and CD34 was demonstrated for the following markers; HIF-1α, CD4, CD8, FOXP3, IRF1, GATA3, CCL2, CCL3, CXCL12 and CCL21. CONCLUSIONS: Combined expression of nestin and CD34 expression is associated with better overall survival possibly by modulating a favorable immune response.
Authors: Marta Sánchez-Díez; Nicolás Alegría-Aravena; Marta López-Montes; Josefa Quiroz-Troncoso; Raquel González-Martos; Adrián Menéndez-Rey; José Luis Sánchez-Sánchez; Juan Manuel Pastor; Carmen Ramírez-Castillejo Journal: Biomedicines Date: 2022-05-06