Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

Abstract

Background: Apolipoprotein C1 (APOC1) has been proved to play a critical role in gastric, breast, lung, and pancreatic cancer. However, the relationship between APOC1 and urinary tumors remains unclear. This study aimed to assess the diagnostic and prognostic value of APOC1 in urinary tumors. Methods: We performed a pan analysis of APOC1 mRNA expression in urinary cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) database. To further investigate the prognostic value of APOC1 expression in urinary cancers, the Kaplan-Meier plotter database was used. Furthermore, we collected the tumor and adjacent normal samples of 32 ccRCC patients to perform qRT-PCR and western blotting assays. A total of 72 cases with ccRCC were analyzed using tissue microarrays (TMAs). Results: Our results based on Kaplan-Meier plotter database indicated that a high expression of APOC1 may lead to poor overall survival (OS, p = 0.0019) in patients with ccRCC. Furthermore, the cancer stages and tumor grade of ccRCC appeared to be strongly linked with APOC1 expression according to UALCAN database. Hence, we reached a preliminary conclusion that APOC1 may play a key role in the tumorigenesis and progression of ccRCC. Furthermore, the Kaplan-Meier survival curve analyses of 72 clinical patients indicated that high expression of APOC1 was associated with poor progression-free survival (PFS, p = 0.007) and OS (p = 0.022). In addition, univariate Cox regression analysis confirmed the significant relationship between APOC1 expression and survival (p = 0.038). The TMAs analysis in combination with the patients' clinicopathological features was also performed. The expression of APOC1 was found to be significantly correlated with the tumor size (p = 0.018) and histological grade (p = 0.016). Conclusions: In conclusion, the findings of our study suggest that APOC1 may serve as a novel diagnostic and prognostic biomarker for ccRCC. Further evidence on the mechanism of APOC1 promoting tumor progression may transform it to a new therapeutic target for the treatment of ccRCC.

Keywords: apolipoprotein C1 (APOC1); biomarker; clear cell renal cell carcinoma (ccRCC); diagnosis; prognosis.

Figure 1

The mRNA expression of APOC1 was significantly increased in urinary tumor tissues, compared to that in normal tissues (*p <0.05).

Figure 2

Higher expression of APOC1 was significantly associated with shorter overall survival in KIRC (p = 0.0019). However, no such association was observed in KIRP (p = 0.0078), despite the high APOC1 levels. Additionally, high APOC1 had no significant association with the overall survival in other urinary tumors, including BLCA (p = 0.22), TGCT (p = 0.17), KICH (p = 0.61), and PRAD (p = 0.52).

Figure 3

(A) The transcript level of APOC1 in different stages of kidney cancers. The expression of APOC1 increased with the development of KIRC, but made no sense for KIRP and KICH. (B) Similarly, the significantly difference in APOC1 expression was also found in ccRCC tumor grades.

Figure 4

(A) PCR results of the 32 ccRCC tumor tissues. The mRNA expression of APOC1 in tumor tissues was significantly higher than that in adjacent tissues (p < 0.01) (B) the APOC1 protein level was significantly higher in tumor tissues than that in adjacent tissues. (C) The western blot analysis of eight ccRCC patients with different tumor grades revealed higher protein expression of APOC1 in patients with higher tumor grade. (D,E) The mRNA and protein expression level of APOC1 was highest in CAKI-2. In addition to CAKI-2 and ACHN, all the other cell lines showed lower APOC1 expression than HK-2, which is considered as a normal tissue cell line (**p < 0.01, ***p < 0.001).

Figure 5

Representative pictures of ccRCC in tissue microarray by IHC, (a) (negative), (b) (weak brown), (c) (moderate brown), (d) (strong brown).

Figure 6

The APOC1 high expression group was associated with decreased overall survival (A) and progression-free survival (B) in 72 ccRCC patients. Log-rank p value was 0.022 for OS, and 0.007 for PFS.