Overexpressing PTTG family genes predict poor prognosis in kidney renal clear cell carcinoma

Abstract

Background: Pituitary tumor transforming genes (PTTG1, PTTG2, and PTTG3P) play key roles in the pathogenesis and development of human cancers. The studies show that overexpression of the PTTG genes is associated with tumor progression and migration. However, the function of the PTTG genes in the prognostic value of kidney renal clear cell carcinoma is rarely known by people.

Methods: The expression of PTTG family genes was analyzed by the ONCOMINE, Human Protein Atlas, GEPIA2, and UALCAN database. The relationship between PTTG family genes expression level and clinical indicators including prognostic data in kidney renal clear cell carcinoma was analyzed by GEPIA2, TCGA portal, and UALCAN. cBioPortal database was used to analyze the genetic mutations of differentially expressed PTTG family members. Similar genes of the PTTG family (90 in total) obtained from GEPIA2 and Metascape were used for GO enrichment to explore the interaction among similar genes. The online tools of Metascape and STRING were used for functional and pathway enrichment analysis.

Results: PTTG1, 2, and 3P mRNA and protein expression upregulated in kidney renal clear cell carcinoma kidney renal clear cell carcinoma patients compared with normal tissues. And higher expression level of PTTG family genes was associated with shorter overall survival (OS) and disease-free survival (DFS). Furthermore, overexpression of the PTTG family genes had been found correlated with individual cancer stages and pathological tumor grades. In addition, 18% of mutations in the PTTG family genes were associated with short-term survival in kidney renal clear cell carcinoma patients.

Conclusions: A single PTTG gene or PTTG family genes as a whole may be a potential prognostic biomarker for kidney renal clear cell carcinoma.

Keywords: Biomarker; KIRC; PTTG; Prognostic.

Fig. 1

Transcriptional expression of PTTGs in 20 different types of cancer diseases (a). Difference of transcriptional expression was compared by students’ t test. Cut-off of p value and fold change were as follows: p value, 0.01; fold change, 1.5; gene rank, 10%; data type, mRNA. Significant changes of PTTGs expression in transcription level between KIRC and normal tissues (ONCOMINE) (b-j)

Fig. 2

mRNA expression of distinct PTTG family members in KIRC and adjacent normal tissues (UALCAN). mRNA expressions of PTTG family members were found to be over-expressed in primary KIRC tissues compared with normal samples (a-c). *p<0.05, **p<0.01, ***p<0.001. Representative immunohistochemistry images of distinct PTTG family members in KIRC tissues and normal tissues (Human Protein Atlas), PTTG3P protein were not expressed in normal renal tissues, while PTTG1 and PTTG2 high and medium expressions were observed in KIRC tissues (d, e)

Fig. 3

Association of mRNA expression of distinct PTTG family members with tumor grades of KIRC patients. mRNA expressions of PTTG family members were significantly related to tumor grades, and as tumor grade increased, the mRNA expressions of PTTGs tended to be higher, individual cancer stages similarly (a-f) *p<0.05, **p<0.01, ***p<0.001

Fig. 4

Prognostic value of mRNA expression of distinct PTTG family members in KIRC patients (UALCAN) (a-c). Prognostic value of protein expression of distinct PTTG family members in KIRC patients (Human Protein Atlas) (d). Prognostic value of mRNA expression of PTTG1, PTTG2 in KIRC patients (TCGAportal) (e, f). Prognostic value of mRNA expression of distinct PTTG family members in KIRC patients (GEPIA) (g)

Fig. 5

Genetic mutation rates of PTTG family genes in KIRC patients of KIRC patients (cBioPortal). Mutation rate (18%) of PTTGs was observed in KIRC patients, their mutation rates were 14%, 4%, and 5% respectively (a). Genetic alterations in PTTGs were associated with shorter OS of KIRC patients (b)

Fig. 6

Co-expression profile of PTTG1 identified (ONCOMINE) (a) mRNA expression of UBE2C in KIRC samples and adjacent normal renal samples (GEPIA) (b). The prognostic value for the expression of UBE2C (GEPIA) (c, d)

Fig. 7

GO functional enrichment analysis predicted four main functions of PTTGs. Functionally similar gene including biological process, cellular components, molecular functions, and KEGG pathway analysis (a-c). PPI network was generated from members of the PTTG family genes and their similar genes (STRING) (d)