陆军军医大学学报 (Jan 2023)

Predictive value of CPT1A and CPT2 expression levels in prognosis of clear cell renal cell carcinoma

  • HUANG Yiqiang,
  • PENG Song,
  • TANG Peng,
  • WANG Ze,
  • XU Jing

DOI
https://doi.org/10.16016/j.2097-0927.202205078
Journal volume & issue
Vol. 45, no. 1
pp. 45 – 53

Abstract

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Objective To explore the expressions of fatty acid degradation related genes carnitine palmitoyltransferase 1A (CPT1A) and carnitine palmitoyltransferase 2 (CPT2) in clear cell renal cell carcinoma (ccRCC) and their prognostic significance. Methods The genes involved in fatty acid degradation and their related metabolites in the ccRCC datasets from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were analyzed by bioinformatic tools. Clinical data of renal carcinoma patients admitted to our hospital from 2007 to 2016 were collected. Immunohistochemical (IHC) staining and Western blotting were performed to detect the levels of CPT1A and CPT2, key genes of fatty acid degradation. The tissue chips of ccRCC were prepared (n=103), and IHC scores of CPT1A and CPT2 were used to estimate the relationship between their expression and prognosis of patients. Subsequently, the prognostic models were constructed and preliminarily evaluated. Results Bioinformatics analysis revealed that CPT1A and CPT2 were key genes involved in palmitylcarnitine metabolism, fatty acid oxidation and renal carcinoma progression. The results of tissue microarray and TCGA cohort showed that ①The expression levels of both CPT1A and CPT2 in ccRCC were lower than those in normal renal tissues (P < 0.05); ②IHC scores indicated that the expression levels of CPT1A and CPT2 were negatively correlated with pathological grade (r=-0.243, P=0.013; r=-0.391, P < 0.01) as well as with TNM stage(r=-0.363, P < 0.01; r=-0.430, P < 0.01); ③Reduced levels of CPT1A and CPT2 were associated with declined disease-free survival (P < 0.01). Moreover, Cox regression analysis showed that CPT2 expression level was an independent prognostic factor for ccRCC patients (P < 0.01). Finally, TNM-CPT1A and TNM-CPT2 models significantly improved the ability of TNM stage alone to predict ccRCC prognosis. Conclusion Compared with patients with high expression, low expression of CPT1A and CPT2 predicted poor prognosis in patients with ccRCC.

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