Dynamic changes of SCGN expression imply different phases of clear cell renal cell carcinoma progression

Abstract

The secretagogin (SCGN) was originally identified as a secreted calcium-binding protein present in the cytoplasm. Recent studies have found that SCGN has a close relationship with cancer. However, its role in the occurrence, progression, and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we utilized a mutual authentication method based on public databases and clinical samples to determine the role of SCGN in the progression and prognosis of ccRCC. Firstly, we comprehensively analyzed the expression characteristics of SCGN in ccRCC in several public databases. Subsequently, we systematically evaluated SCGN expression on 252 microarrays of ccRCC tissues from different grades. It was found that SCGN was absent in all the normal kidney tissues and significantly overexpressed in ccRCC tumor tissues. In addition, the expression level of SCGN gradually decreased with an increase in tumor grade, and the percentage of SCGN staining positivity over 50% was 86.7% (13/15) and 73.4% (58/79) in Grade1 and Grade2, respectively, while it was only 8.3% (12/144) in Grade3, and the expression of SCGN was completely absent in Grade4 (0/14) and distant metastasis group (0/4). Additionally, the expression of SCGN was strongly correlated with the patient's prognosis, with the higher the expression levels of SCGN being associated with longer overall survival and disease-free survival of patients. In conclusion, our results suggest that reduced expression of SCGN in cancer cells is correlated with the progression and prognosis of ccRCC.

Keywords: Biomarker; Heterogeneity; Occurrence; Prognosis; SCGN; ccRCC.

Fig. 1

SCGN mRNA levels are upregulated in ccRCC. A A Venn diagram: the origin of SCGN. B Expression of SCGN mRNA in pan-cancer. C Comparison of transcript levels of SCGN in cancer and normal tissues in the TCGA cohort. D Comparison of transcript levels of SCGN in cancer and normal tissues in the CPTAC cohort. E Comparison of transcript levels of SCGN in cancer and normal tissues in the GSE40435 cohort

Fig. 2

SCGN protein is upregulated in ccRCC. A Comparison of SCGN expression in cancer and normal tissues in the CPTAC database. B IHC of SCGN in cancer and normal tissues in the HPA database. C IHC of SCGN in cancer and normal tissues in our cohort. D Nuclear positive ratio statistical analysis of cancers and normal tissues under IHC in our cohort

Fig. 3

As ccRCC progressed SCGN expression was gradually decreased. A The relationship between SCGN mRNA level and stages in TCGA cohort. B The relationship between SCGN mRNA level and WHO/ISUP nuclear grades in TCGA cohort. C The relationship between SCGN protein level and stages in CPTAC cohort. D The relationship between SCGN protein level and WHO/ISUP nuclear grades in CPTAC cohort. E HE and IHC of SCGN of ccRCC patients with nuclear grade 1. F HE and IHC of SCGN of ccRCC patients with nuclear grade 2. G HE and IHC of SCGN of ccRCC patients with nuclear grade 3. H HE and IHC of SCGN of ccRCC patients with nuclear grade 4. I Statistical analysis of nuclear positive ratio of tissue microarrays between different ccRCC grades. J Intratumoral heterogeneous expression of SCGN in ccRCC

Fig. 4

Absence of SCGN expression in distant metastases of ccRCC. A Comparison of SCGN expression between primary and distant metastatic foci in ccRCC. B HE and IHC of ccRCC with lung metastasis. C Comparison of SCGN expression between cell lines of ccRCC

Fig. 5

Patients with high SCGN expression have a longer survival time. A–B In the TCGA cohort, patients were grouped according to SCGN expression to compare OS and DFS. C In the E-MEAB-1980 cohort, patients were grouped according to SCGN expression to compare OS. D In the CPTAC cohort, patients were grouped according to SCGN expression to compare OS