Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance

Abstract

GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS). On the contrary, increased numbers of GOLPH2-positive and GOLPH3-positive TAMs were observed in thinner, non-ulcerated tumors, with brisk lymphocytic reaction and absent lymphangioinvasion. Distant metastases were not observed among patients with high numbers of GOLPH2-positive TAMs. Increased expression of either protein in TAMs was related to prolonged CSOS and DFS. Similarly, GOLPH3-expressing CAFs were more frequent in thin melanomas with low mitotic rate, without ulceration and lymphangioinvasion. Moreover, increased GOLPH3-positive CAFs correlated with the absence of regional or distant metastases, and with longer CSOS and DFS. GOLPH2 expression was not observed in CAFs. Our results suggest that GOLPH2 and GOLPH3 play a role in melanoma progression and are potential targets for molecular-based therapies.

Effects of hub genes on the clinicopathological and prognostic features of lung adenocarcinoma

“…GOLM1 is a resident cis-Golgi membrane protein. On the surface of the Golgi apparatus, there is an extensive C-terminal, coiled-coil domain and a single N-terminal transmembrane domain (44). It has been confirmed that the Golgi apparatus serves an active role in cell migration, which can be activated by post-translational modification and prominent alterations (45).…”

A CREB3-regulated ER–Golgi trafficking signature promotes metastatic progression in breast cancer

“…These data point toward the potential use of Golgi trafficking genes as prognostic markers in cancer. To date, several Golgi-associated genes have been studied as prognostic markers in cancer, including Golgi phosphoprotein-3 (GOLPH3), Golgi protein 73 (GP73) and progestin and adipoQ receptor 3 (PAQR3) 57 – 60 . Further studies focused on elucidating the mechanisms regulating Golgi secretion capacity are warranted and may lead to therapeutic targeting of discrete components of this pathway in metastatic disease.…”

Nucleoli cytomorphology in cutaneous melanoma cells – a new prognostic approach to an old concept

“…In our study we observed a statistically significant correlation between the presence of macronucleoli and increased number of nucleoli (polynucleolization) and decreased expression of GOLPH3 protein in tumor-associated macrophages (TAMs). Having no factual insight into the role of GOLPH3 in TAMs, we only speculate that the reduced GOLPH3 immunoreactivity in TAMs may be associated with stable prooncogenic M2 phenotype [ 19 ]. Due to the lack of clinical and molecular data careful functional investigations are needed to explore the roles of tumor-associated macrophages in melanoma.…”