Overexpression of cytoplasmic dynamin 2 is associated with worse outcomes in patients with clear cell renal cell carcinoma

Article type: Research Article

Authors: Safaei, Sadegh^{a; b; 1} | Sajed, Roya^{a; b; 1} | Saeednejad Zanjani, Leili^{b; *} | Rahimi, Mandana^c | Fattahi, Fahimeh^{a; b} | Ensieh Kazemi-Sefat, Golnaz^a | Razmi, Mahdieh^b | Dorafshan, Shima^{a; b} | Eini, Leila^{b; d} | Madjd, Zahra^{a; b; *} | Ghods, Roya^{a; b; *}

Affiliations: [a] Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran | [b] Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran | [c] Hasheminejad Kidney Center, Pathology Department, Iran University of Medical Sciences (IUMS), Tehran, Iran | [d] Division of Histology, Department of Basic Science, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

Correspondence: [*] Corresponding authors: Roya Ghods, %****␣cbm-35-cbm210514_temp.tex␣Line␣100␣**** Oncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, Iran. Tel.: +98 218 670 3212; Fax: +98 218 862 2608; E-mail: [email protected]; [email protected]. Zahra Madjd, Oncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, Iran. Tel.: +98 218 670 3212; Fax: +98 218 862 2608; E-mail: [email protected]; [email protected]. Leili Saeednejad Zanjani, Oncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, Iran. Tel.: +98 218 670 3212; Fax: +98 218 862 2608; E-mail: [email protected].

Note: [1] Sadegh Safaei and Roya Sajed contributed equally to this manuscript as cofirst authors.

Abstract: BACKGROUND: Dynamin 2 (DNM2) involved in tumor progression in various malignancies. OBJECTIVE: For the first time, we evaluated DNM2 expression pattern, its association with clinicopathological characteristics and survival outcomes in RCC subtypes. METHODS: We evaluated the DNM2 expression pattern in RCC tissues as well as adjacent normal tissue using immunohistochemistry on tissue microarray (TMA) slides. RESULTS: Our findings revealed increased DNM2 expression in RCC samples rather than in adjacent normal tissues. The results indicated that there was a statistically significant difference between cytoplasmic expression of DNM2 among subtypes of RCC in terms of intensity of staining, percentage of positive tumor cells, and H-score (P= 0.024, 0.049, and 0.009, respectively). The analysis revealed that increased cytoplasmic expression of DNM2 in ccRCC is associated with worse OS (log rank: P= 0.045), DSS (P= 0.049), and PFS (P= 0.041). Furthermore, cytoplasmic expression of DNM2 was found as an independent prognostic factor affecting DSS and PFS in multivariate analysis. CONCLUSIONS: Our results indicated that DNM2 cytoplasmic expression is associated with tumor aggressiveness and poor outcomes. DNM2 could serve as a promising prognostic biomarker and therapeutic target in patients with ccRCC.

Keywords: DNM2, renal cell carcinoma (RCC), ccRCC, immunohistochemistry (IHC), tissue microarray (TMA)

DOI: 10.3233/CBM-210514

Journal: Cancer Biomarkers, vol. 35, no. 1, pp. 27-45, 2022