Prognostic relevance of autophagy-related markers p62, LC3, and Beclin1 in ovarian cancer. 2022

Ljubiša Jovanović, and Aleksandra Nikolić, and Sandra Dragičević, and Milena Jović, and Radmila Janković
Ljubiša Jovanović, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, jovanovicljubisa18@gmail.com.

OBJECTIVE To analyze the expression of autophagy markers p62, LC3, and Beclin1 in ovarian cancer tissue and evaluate the prognostic potential of these markers. METHODS The study enrolled 328 patients: 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. The expression of p62, LC3, and Beclin1 was analyzed in central and invasive tumor segments with immunohistochemistry combined with tissue microarray. The expression levels of the analyzed markers were correlated with relevant histopathology parameters. RESULTS The expression of all analyzed markers was most remarkable in epithelial ovarian carcinoma. There was a strong positive correlation between the expressions of p62 and LC3, while these two markers negatively correlated with Beclin1. High-grade serous carcinoma had higher p62 and LC3 levels, and lower Beclin1 levels than other tumor types. This expression profile was also observed in more advanced tumor stages. CONCLUSIONS Prominent p62 and LC3 expression in combination with weak Beclin1 expression in high-grade serous carcinoma indicates potential for the application of autophagy inhibitors in patients with this tumor subtype.

UI MeSH Term Description Entries
D008869 Microtubule-Associated Proteins High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules. Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071186 Beclin-1 An autophagy related protein which functions as a core subunit of PHOSPHATIDYLINOSITOL 3-KINASE MULTIPROTEIN COMPLEXES. It mediates the formation of phosphatidylinositol 3-phosphate and functions in AUTOPHAGY, where it is required for maturation of the AUTOPHAGOSOME. It also functions in ENDOCYTOSIS and CYTOKINESIS as part of a separate complex. Beclin-1 associates with INTRACELLULAR MEMBRANES and interacts with the PROTO-ONCOGENE PROTEINS C-BCL-2 and BCL-X PROTEIN. ATG-6 Protein,ATG6 Protein,Beclin-1 Protein,Beclin1,Coiled-coil Myosin-like Bcl2-interacting Protein,GT197 Protein,ATG 6 Protein,Beclin 1,Beclin 1 Protein,Coiled coil Myosin like Bcl2 interacting Protein
D000077216 Carcinoma, Ovarian Epithelial A malignant neoplasm that originates in cells on the surface EPITHELIUM of the ovary and is the most common form of ovarian cancer. There are five histologic subtypes: papillary serous, endometrioid, mucinous, clear cell, and transitional cell. Mutations in BRCA1, OPCML, PRKN, PIK3CA, AKT1, CTNNB1, RRAS2, and CDH1 genes are associated with this cancer. Epithelial Ovarian Cancer,Epithelial Ovarian Carcinoma,Ovarian Cancer, Epithelial,Ovarian Epithelial Cancer,Ovarian Epithelial Carcinoma,Cancer, Epithelial Ovarian,Cancer, Ovarian Epithelial,Carcinoma, Epithelial Ovarian,Epithelial Cancer, Ovarian,Epithelial Carcinoma, Ovarian,Epithelial Ovarian Cancers,Epithelial Ovarian Carcinomas,Ovarian Carcinoma, Epithelial,Ovarian Epithelial Cancers,Ovarian Epithelial Carcinomas
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy

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