Ollier disease mainly occurs in the first decade of life [4]. The most common malignancy of OD is chondrosarcoma. In the present study, we analyzed OD related microarray datasets from the GEO database to screen for DEGs of Ollier chondrosarcoma and identified candidate hub genes. The relationship between immune and Ollier chondrosarcoma was firstly revealed.
KEGG pathway analysis showed that phagosome and ECM-receptor interaction pathways were closely related to DEGs. Phagocytosis is the main process of phagosome pathway, and can be carried out by the cell of relatively large particles (> 0.5 mm) into vacuoles. [11]. Normal means of phagosome maturation could promote the immune response [12]. In our study, phagosome pathway mainly included 11 DEGs. Among them, HLA-DMB, HLA-DMA and HLA-DRA are all related to MHC Class II antigen. Last studies have shown that ECM-receptor interaction pathway is also up-regulated in prostate cancer tissue [13].
GO enrichment analysis revealed that significant ontology categories of upregulated DEGs included ECM constituent, glycosaminoglycan binding, and antigen processing and presentation of peptide or polysaccharide antigen via MHC class II. Some studies have demonstrated the composition of the micro-environment play a considerable role in the whole procession of tumors [14]. The peritumoral stroma exists in an extensive ECM composed of a lot of molecules, including glycoproteins, and so on [15]. Hyaluronan(HA) influences whole biological activities in the ECM [16]. A previous study found that HA increased significantly in chondrosarcoma patients [17]. The necrotic zone in vivo is a centre where HLA-DR monocytes are gathered and start to transform into chondrosarcoma [18].
Immune filtration analysis helps us understand the proportion of immune microenvironment. In our study, M0 macrophages are of statistical significance. Richert [19] reported that the M0 cells were characterized by high plasticity and they were both tumor-associated macrophages participating the metastatic spreading. B cells naïve has been proved to perform a role in autoimmune disease such as multiple sclerosis[20]. Recent study revealed that C-type lectin CLEC16A expressed in the surface of naïve B cells participated in MHC Class II pathway[21].
7 hub genes were selected from PPI network. Among them, three hub genes COL3A1, COL11A1 and VCAN were in module1. Module1 was mainly enriched in GO terms of chondrocyte development, post-translation protein phosphorylation and ECM organization pathway. Changes in amount and composition of ECM are considered as a biomarker of tumour development [22].
ITGB1 is regarded as the most significant receptor of COL2A1 [23]. It can mediate COL2A1 related effect on chondrocyte hypertrophy [24]. In oral squamous cell carcinoma (OSCC), THBS1 is a tumor specificity ECM protein induced by TGFB1 and improves the migration ability of cancer cells [25]. It does not directly protect chondrocytes but could reduce inflammation [26].
CCND1 and CCL2 belong to module2 in PPI network. Module2 was mainly enriched in GO terms of antigen processing and presentation, and MHC class II antigen presentation pathway. Romeo S [27] reported that CCND1 was lower expression in high-grade central chondrosarcoma, compared with chondromyxoid fibroma. This phenomenon reflected impairment of cell cycle progression and of cell-cell adhesions in malignant tumors. PTHR1 can directly control the activation of the cyclinD1 promoter [28]. The expression of PTHR1 was higher with increasing histological grade in chondrosarcoma [27]. Chemokine ligand2 (CCL2) belongs to the CC chemokine family. CCL2 is related to the migration of chondrosarcoma. A recent study indicated that CCL2 accelerated the migration of chondrosarcoma cells through the CCR2 receptor and NF-κB signal transduction pathway [29]. These results square with the functional enrichment analysis results of DEGs and can reflect the primary function of DEGs.
By putting the results together, we found that phagosome pathway was a key link in the presentation of antigens MHC Class II, and linked innate and adaptive immunity [30]. The two terms are both related to upregulated DEGs. Chondrosarcomas and central nervous system tumors are seen as tumors with the highest frequency IDH mutations [5]. A previous study revealed that the maturation of type IV collagen which could result in fragile basement membranes was inhibited in IDH1 R132H knock-in mice [31]. IDH1/2 mutation has also been reported in conventional (central and periosteal) and dedifferentiated chondrosarcoma [31]. In our analysis, IDH1 and IDH2 are both slightly up-regulated. COL4A1 encoding type IV collagen was important in our study, and it played the same role as IDH in regulating basement membrane.
A study based on cDNA, comparing OD with solitary chondrosarcoma samples (n = 7, three with OD). There are no statistical difference in biology between them in this study. This study is limited to the samples available are few because OD is sporadic. While, this study found that JunB protein was significantly lower in enchondromas compared with chondrosarcoma. JunB may be identified as a good diagnostic marker for malignancy [32]. Our study can also support this conclusion, JunB is also a DEG in our study.