Transcriptional Levels of GINS members in Sarcoma Patients
Four members (GINS1, GINS2, GINS3, GINS4) of GINS family has been discovered in previous studies. They were found to be linked to many different types of tumor. The ONCOMINE database was used to compare the dissimilarity of transcription levels of GINS between cancer and normal samples. We detected that the transcription levels of GINS were upregulated in several cancers including cervical cancer, colorectal cancer, lung cancer and sarcoma. Especially, all the transcription levels of the four subunits of GINS were upregulated in sarcoma tissues (figure 1). In table 1, as we showed, the mRNA expression level of GINS1 was significantly upregulated in sarcoma patients. In Detwiller Sarcoma dataset, the mRNA expression of GINS1 in pleomorphic liposarcoma was higher than in normal samples, with a fold change of 10.222. In fibrosarcoma, malignant fibrous histiocytoma and round cell liposarcoma, GINS1 was also more highly expressed than in normal samples, and the fold changes were 9.773, 10.455 and 6.478. The Barretina Sarcoma dataset provided us that the expression levels of GINS1 were higher in pleomorphic liposarcoma (fold change = 4.135), myxofibrosarcoma (fold change = 5.272), leiomyosarcoma (fold change = 4.566), dedifferentiated liposarcoma (fold change = 3.204) and myxoid/round cell liposarcoma (fold change = 3.412) than in normal samples.
We could also learn from the Detwiller et al. that GINS2 was overexpressed in pleomorphic liposarcoma, malignant fibrous histiocytoma, fibrosarcoma, round cell liposarcoma with fold changes of 7.103, 6.800, 6.258 and 4.712 respectively. Highly expressed GINS2 was also found in Pleomorphic Liposarcoma, Myxofibrosarcoma, Leiomyosarcoma, Dedifferentiated Liposarcoma, Myxoid/Round Cell Liposarcoma, with fold changes of 2.231, 2.729, 2.892, 2.046 and 2.351 respectively, compared with normal tissues through Barretina Sarcoma dataset. GINS3 was found upregulated with a fold change of 5.246 in Malignant Fibrous Histiocytoma in Detwiller datasets. In Detwiller datasets, highly overexpressed GINS4 was reported in Fibrosarcoma (fold change = 2.441).
Comparison of The Expression of GINS mRNAs in Sarcoma and Normal Tissues
Using the GEPIA dataset, we compared the expression of GINS mRNAs in sarcoma and normal tissues, it indicated that the expression levels of GINS1, GINS2 and GINS3 in sarcoma were statistically higher than in normal samples. The expression level of GINS4 in sarcoma was also higher than in normal samples, but with no significance. (figures 2A- 2F).
GINS Translational Factors Expression in Sarcoma Cell Lines
By interrogating CCLE, we detected the transcription level of GINS members in many types of cancer cell lines, and got the conclusion that GINS1, GINS2 GINS3 and GINS4 were highly expressed in sarcoma cell lines including Ewings sarcoma, osteosarcoma and chondrosarcoma. (figures 3A- 3D).
The Prognostic Value of GINS members in Sarcoma
The GEPIA and Kaplan-Meier Plotter was used to make the investigation of the prognostic ability of GINS1, GINS2, GINS3 and GINS4 expression levels in sarcoma. We can see from the (figure 4A-4C), increased GINS1-3 were found to be linked to poor overall survival (OS) (p<0.05), disease-free survival (DFS) (p<0.05) and relapse-free survival (RFS) (p<0.05). Nevertheless, increased GINS4 was discovered tend to have significant association with poor RFS. To sum up, GINS1-4 were prognostic factors for sarcoma.
Co-expressed Genes of GINSes, and the Correction between
GINSes in Sarcoma
ONCOMINE and GEPIA datasets were used in this part. Analyses of co-expressed genes of GINS1 and the correction between GINS1 in sarcoma were conducted in the Barretina dataset. We obtained that GINS1 was highly corrected with ZWINT, CDK1, KIAA0101, RRM2, RACGAP1, BUB1B, NUSAP1, PRC1, TOP2A and TTK (figure 5A). We searched for this of GINS2 in Barretina datasets likewise, and found its positive correction is with MCM2, RFC4, MLF1IP, DTL, TYMS, POLE2, RRM1, LIG1, EZH2 and CENPM (figure 5A). The data about co-expressed genes of GINS3 were from the TCGA Sarcoma (http://tcga-data.nci.nih.gov/tcga/), our study pointed out that GINS3 was positively corrected with PRSSS4, CCDC113, CSNK2A2, C16orf80, MMP15, C16orf57, ZNF319, TEPP, CNC81 and KIFC3 (figure 5A). As for GINS4, we discovered it was positively corrected with CKAP2L, BRIP1, ZNF367, MCM10, CENPM, MYBL2, CDC45, MTSS1, GABRR3 and FANCB in Nakayama dataset (figure 5A). Our study also encompassed the association among GINS1, GINS2, GINS3 and GINS4 through GEPIA, revealing that GINS1 was positively corrected with GINS2 (R=0.67, p＜0.05), GINS3 (R=0.6, p＜0.05), GINS4 (R=0.64, p＜0.05) (figure 5B). And GINS2 was positively corrected with GINS3 (R=0.55, p＜0.05) and GINS4 (R=047, p＜0.05) (figure 5B), also, GINS3 was positively corrected with GINS4 (R=0.4, p＜0.05) (figure 5B).