Identification of key biomarkers involved in osteosarcoma using altered modules

Abstract

ABSTRACT. The aim of this study was to screen for key biomarkers of osteosarcoma (OS) by tracking altered modules. Protein-protein interaction (PPI) networks of OS and normal groups were constructed and re-weighted using the Pearson correlation coefficient (PCC), respectively. The condition-specific modules were explored from OS and normal PPI networks using a clique-merging algorithm. Altered modules were identified by a maximum weight bipartite-matching method. The important biological pathways in OS were identified by a pathway-enrichment analysis using genes from disrupted modules. The most important genes in these pathways were selected as key biomarkers. Finally, the mRNA and protein expressions of hub genes in OS bone tissues were analyzed using reverse transcription-polymerase chain reaction and western blotting, respectively. We identified 703 and 2270 modules in normal and disease networks, respectively; 150 altered modules were identified from among these and explored. We identified 10 important pathways based on gene pairs with altered PCC > 1 in the disrupted modules (P < 0.01), and PCNA, ATP6V1C2, ATP6V1G3, FEN1, CDC7, and RPA3 (expressed in these pathways) were selected as key genes of OS. We observed that these genes (and the proteins they encoded) were differentially expressed between normal and OS samples (P < 0.01) (excluding ATP6V1C2, whose protein expression did not differ significantly). Therefore, we identified 5 gene signatures that may be potential biomarkers for the detection and effective therapy of OS.

The Clinical Significance of the Expression of FEN1 in Primary Osteosarcoma

“…It is worth mentioning that Liu et al have concluded that FEN1, identified as a key gene associated with OS development, might be a potential biomarker for diagnosis and treatment of this tumor by systematically tracking the altered modules in the reweighted normal and OS PPI networks. 28 In the present study, we found that osteosarcoma patients, who showed high expression of FEN1, had shorter OS time and PFS time. Meanwhile, multivariate analysis indicated that FEN1 expression was an independent prognostic factor for osteosarcoma patients.…”

Cullin-1 Regulates MG63 Cell Proliferation and Metastasis and is a Novel Prognostic Marker of Osteosarcoma

“…These tumors are typically rapid growers with high metastatic potential, especially to the lungs and bones (5). Although treatment with surgery and neoadjuvant chemotherapy appears to cure 60%-70% of cases (6), the 5-year survival rate Research investigating the mechanism of osteosarcoma development has primarily focused on chromosomal abnormalities, genetic alterations of tumor suppressor genes, activation of oncogenes and dysregulation of major signaling pathways (12). Therefore, the exact role of CUL1 in the tumorigenesis and progression of osteosarcoma has yet to be established.…”

“…Research investigating the mechanism of osteosarcoma development has primarily focused on chromosomal abnormalities, genetic alterations of tumor suppressor genes, activation of oncogenes and dysregulation of major signaling pathways (12). Therefore, the exact role of CUL1 in the tumorigenesis and progression of osteosarcoma has yet to be established.…”

V-ATPases and osteoclasts: ambiguous future of V-ATPases inhibitors in osteoporosis

“…Subunit G3: Subunit G3 is expressed in kidney and rat epididymis 105 , 109 . Its protein is used as a novel immunohistochemical marker for differentiating subtypes of chromophobe renal cell carcinoma (RCC) including clear cell, papillary RCCs 114 , 115 , and osteosarcoma 116 .…”