Abstract
Background Inhibitors of apoptosis proteins such as cIAP-1 and cIAP-2 have recently emerged as the key mechanism in resistance to apoptosis in various cancers and lead to cell survival. Therefore, the present study aimed to evaluate the cIAP-1 and cIAP-2 expression in breast cancer patients, as well as their association with overall patient survival. Methods Histopathologically confirmed 100 invasive ductal carcinoma patients and healthy controls were included in the present study. Total RNA extraction was done from the serum sample of the patients; further, 100 ng of total RNA was used to synthesise cDNA from patients' as well as from healthy controls' serum. Quantitative real-time PCR was performed using the maxima SYBR Green dye to study the expression of cIAP-1 and cIAP-2, and beta-actin was used as the internal control. Results The study observed that breast cancer patients had 13.50 mean fold increased cIAP-1 mRNA and 8.76 mean fold increased cIAP-2 mRNA expression compared to the control subjects. Breast cancer patients in the TNM stages I, II, III, and IV showed 9.54, 11.80, 15.19, and 16.83 mean fold increased cIAP-1 mRNA expression (p=0.004). Distant organ metastasis, (p=0.008), PR status of breast cancer patients (p < 0.0001), and HER2 status of breast cancer patients (p < 0.0001) were found to be associated with cIAP-1 mRNA expression. Breast cancer patients with different TNM stages such as stages I, II, III, and IV showed 7.8, 8.09, 7.97, and 12.85 mean fold increased cIAP-2 mRNA expression (p=0.0002). Breast cancer patients with distant organ metastases status were found to be associated with cIAP-2 mRNA expression (p < 0.0001). Breast cancer patients with <13-fold and >13-fold cIAP-1 mRNA expression showed 37.39 months and 34.70 months of overall median survival, and the difference among them was found to be significant (p=0.0001). However, cIAP-2 mRNA expression among <8-fold and >8-fold mRNA expression groups showed 35 months and 27.90 months of overall median survival time (p < 0.0001). Higher cIAP-1 mRNA expression was linked with smoking and alcoholism among the breast cancer patients (p < 0.0001 and p < 0.0001). Significant association of higher cIAP-1 mRNA expression was found with the advancement of the disease, while higher mRNA expression of cIAP-1 was associated with distant organ metastases in ROC curve analysis. Conclusion The present study suggested that increased cell-free cIAP-1 and cIAP-2 mRNA expression was correlated with the advancement of disease, progression of disease, and overall reduced patient survival. Cell-free cIAP-1 and cIAP-2 mRNA expression could be the predictive indicator of the disease.
Highlights
Apoptosis is a highly conserved cell death mechanism carried out by high machinery in our body, and the hallmark step of this mechanism includes the activation of aspartic acidspecific cysteine proteases called caspases [1]
E cIAP-1 and cIAP-2 mRNA expression was done by quantitative RT-PCR using SYBR Green I technology, and the beta-actin gene was used as the housekeeping control to analyse the fold change in mRNA expression. e primer sequences for cIAP-1 and cIAP-2 mRNA and beta-actin mRNA amplification are depicted in Table 1. e cIAP-1 and cIAP-2 mRNA expression study was executed by using the programme for 40 cycles, with the first denaturation step at 94°C for 35 s, annealing was for 40 s to 600°C with various temperatures, and extension was done at 72°C for 40 s, and the final reaction volume was maintained to 20 μl. e final step for extension was at 72°C for 5 minutes
We found that 13.50 mean fold increased cIAP-1 and 8.76 mean fold increased cIAP-2 mRNA expression was observed in breast cancer patients
Summary
Apoptosis is a highly conserved cell death mechanism carried out by high machinery in our body, and the hallmark step of this mechanism includes the activation of aspartic acidspecific cysteine proteases called caspases [1]. Breast cancer patients in the TNM stages I, II, III, and IV showed 9.54, 11.80, 15.19, and 16.83 mean fold increased cIAP-1 mRNA expression (p 0.004). Breast cancer patients with different TNM stages such as stages I, II, III, and IV showed 7.8, 8.09, 7.97, and 12.85 mean fold increased cIAP-2 mRNA expression (p 0.0002). Breast cancer patients with distant organ metastases status were found to be associated with cIAP-2 mRNA expression (p < 0.0001). Breast cancer patients with 13-fold cIAP-1 mRNA expression showed 37.39 months and 34.70 months of overall median survival, and the difference among them was found to be significant (p 0.0001). E present study suggested that increased cell-free cIAP-1 and cIAP2 mRNA expression was correlated with the advancement of disease, progression of disease, and overall reduced patient survival. Cell-free cIAP-1 and cIAP-2 mRNA expression could be the predictive indicator of the disease
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