br Apo A which mediates the
Apo-A1, which mediates the reverse transport of cholesterol from peripheral cells to the liver for excretion, is a major high-density lipo-protein (HDL) component in plasma, constituting about 70% of the apolipoprotein (APO) content of HDL particles. In the lipid-bound state, Apo-A1 governs lipid transport, receptor recognition and other func-tions, including activation of lecithin-cholesterol acyltransferase, which converts cholesterol to cholesterol ester (Sengupta and Mukhopadhyay, 2016). Apo-A2 is the second-most abundant apolipoprotein of HDL 20% of HDL protein (Moradi et al., 2017).
The diagnostic value of Apo-A1 in early tumor detection was re-ported in many subsequent studies in which, increased levels of Apo-A1 were found in various malignant tumors. Apo-A1 precursor was sig-nificantly increased suggesting it could be an eﬀective potential bio-marker in the diagnosis of thyroid cancer (Li et al., 2014).
In cancer, lipid and cholesterol homeostasis is often dysregulated to facilitate the cancer cells' increased demand for these building blocks which are required for proliferation and evasion of apoptosis. To this end, tumor cells can manipulate their intracellular cholesterol level by reducing expression of ABCA1 which eﬄuxes cholesterol and in-creasing the expression of SR-B1 which influxes cholesterol. This phe-nomenon has been reported in several prostate, colon and Taranabant cancers.
Fig. 3. Levels of Apo-A1 expression by protein normalization ratio in urine samples of the studied group.
Fig. 4. Levels of Apo-A2 expression by protein normalization ratio in urine samples of the studied groups.
The present study showed that the level of Apo-A1 and Apo-A2 in voided urine was significantly higher in malignant group than cystitis (benign) group and normal healthy group with 100% sensitivity and 100% specificity for both markers and 100% PPV and 100% NPV and 100% AUC for two markers. This result was in agreement with many studies. Li et al., have reported that Apo-A1 was detected in all urine's samples (n = 40) of bladder cancers (Li et al., 2014). In another study they found that Apo-A1 have higher level in urine from bladder cancer patients (Hammam et al., 2015). Similarly, Chen et al., found that the average levels of Apo-A1, Apo-A2 were high in cancer group compared to controls (Chen et al., 2010). In another study they found that 12 proteins including Apo-A1 and Apo-A2 represent potential urinary biomarker candidates for detection of bladder cancer (Chen et al., 2012). In another study, apolipoproteins Apo-A1 and Apo-A2, were present at elevated levels in bladder cancer urine specimens (Chen et al., 2013). Results also showed that both Apo-A1 and Apo-A2 levels in blood of three groups were measured without any significant dif-ference between normal and bladder cancer group. At the present time, we do not know the mechanism involved significantly increased of urinary ApoA1 and ApoA2 in bladder cancer, while not changed in the blood. Further studies of these markers on large number of patients along with follow-up of the patients for tumor recurrence are re-commended.
This study revealed that Apo-A1 and Apo-A2 protein levels in urine could be used as a reliable diagnostic agent as well as screening bio-marker which is characterized with being highly sensitive and non-in-vasive.
Each subject signed an informed consent before participating to the study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Data of ROC curves of Apo-A1 and Apo-A2 in urine and blood.
1 - Specificity
1 - Specificity
ROC Cut oﬀ value Sensitivity Specificity Positive predictive value (PVP) Negative predictive value (NPV) AUC*
AUC* represent accuracy.
Correlations between urinary Apo-A1and Apo-A2 as well as other laboratory data of all malignant group.
Variables Urinary Apo-A1 Urinary Apo-A2
R p-value R p-value
Correlation of urinary levels of ApoA-1and Apo-A2 with clinic-pathological parameters in the malignant group (n = 50) using t-test:
Clinicopathological Mean ± SD of P value of Mean ± SD P value of factor urinary Apo- urinary of urinary urinary
This study was not funded by any grants or other financial support.