Significant Implications of APOA1 Gene Sequence Variations and Its Protein Expression in Bladder Cancer.

Javid A Magray,Muzzain Khateeb,Zafar A Shah,Arif Hamid,Mohammad S Wani,Sheikh Mansoor,Aabid Koul,Wafa Charifi,Iqbal Qasim,Arshad A Pandith,Ajaz Ahmad,Shahid M Baba

doi:10.3390/biomedicines9080938

Abstract

Apolipoprotein A1 (APOA1) is a potential biomarker because of its variable concentration in different types of cancers. The current study is the first of its kind to evaluate the association between the APOA1 genotypes of −75 G/A and +83 C/T in tandem with the APOA1 protein expression in urine samples to find out the risk and potential relationship for differentially expressed urinary proteins and APOA1 genotypes. The study included 108 cases of bladder tumors and 150 healthy controls that were frequency matched to cases with respect to age, sex, and smoking status. Genotyping was performed using PCR-RFLP and the urinary expression of the APOA1 protein was done using ELISA. Bladder tumor cases were significantly associated with the APOA1 −75 AA genotype (p < 0.05), while the APOA1 +83 C/T heterozygotes showed an association with cases (p < 0.05). The overall distribution of the different haplotypes showed a marked difference between the cases and controls in GT when compared with the wild type GC (p < 0.03). Bladder tumor cases that carried the variant genotype APOA1 −75AA were found more (70.0%) with a higher expression (≥20 ng/mL)of the APOA1 urinary protein and differed significantly against wild type GG (p = 0.03). Again, in low grade bladder tumors, urinary APOA1 protein was exhibited significantly more (52.4% vs. 15.4% high grade) with a higher expression (≥20 ng), while high grade tumor cases (84.6% vs. 47.5% low grade) showed a lower APOA1 expression (<20 ng/mL) (O.R = 6.08, p = 0.002). A strong association was observed between APOA1 −75G/A and risk for bladder tumor and its relation to urinary protein expression, which substantiates its possible role as a marker for the risk assessment of the disease and as a promising diagnostic marker for different grades of malignant bladder tumors.

Highlights

The latter report seems to be in complete accordance with our study, with only the exception that we found being the association of Apolipoprotein A1 (APOA1) +83 C/T in bladder tumor cases with a heterozygous condition (+83 CT)
The fact that a marked reduction in APOA1 levels occur during inflammation corroborates well with our findings, where we found a definite correlation between a lower expression of APOA1 with higher bladder tumor grades and stages
The APOA1 combined haplotypic effect confers a significant risk for bladder tumors

Summary

Introduction

Of all cancer cases [1] It is a cancer of the environment and age where the incidence rates increase with age, peaking in the eighth decade of life, and a strong association has been documented between environmental toxins, smoking, and urothelial cancer formation [2,3,4]. Apart from these risk factors, there are circumstances where the disease develops without or with very limited exposure to the risk factors.

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