VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients

Abstract

AIM: The main objectives of this article were to evaluate the association of voltage-dependent anion channel 1 (VDAC1) expression with Cytochrome C (Cytc) protein, various clinicopathological features and prognosis in patients diagnosed with breast cancer (BC). Meanwhile, the correlation of Cytc expression with various clinical features and 5-year disease-free survival (5-DFS) of BC is also investigated. Methods: Expression of VDAC1 protein and Cytc protein was conducted in 219 BC patients and 60 benign breast lesions by immunohistochemical (IHC) analysis. Results: In our study, VDAC1 protein expression was significantly increased while Cytc protein was decreased in breast tumor tissues (P = 0.015 and P = 0.029, respectively). High expression of VDAC1 is conversely associated with Cytc expression in BC, especially in triple-negative breast cancer (TNBC) (P = 0.011 and P = 0.004, respectively). Interestingly, high expression of VDCA1 not only had a significant association with advanced TNM stage, histological grade, LNM, HER2 gene amplification and recurrence (P < 0.05), but also displayed a poorer 5-DFS (P < 0.001) in BC. The multivariate Cox proportional hazard model demonstrated VDAC1 as a novel independent poor prognostic factor in BC (P = 0.001). Strikingly, our study also showed the prognostic significance of VDAC1 in triple-negative breast cancer in particular. Furthermore, low expression of Cytc was found to be correlated with histological grade, ER status, PR status and recurrence in BC (P < 0.05). Kaplan-Meier analysis indicated that low Cytc expression was associated with poorer survival and high mortality rate (P = 0.007). Cytc protein expression also served as a novel independent prognosis parameters in BC patients (P = 0.035). Conclusion: Our findings firstly revealed that VDAC1 was elevated in BC tissues and conversely associated with Cytc. Furthermore, high VDAC1 protein was associated with reduced 5-DFS and could be acted as an independent poor prognostic factor not only in breast cancer in general, but also in TNBC in particular. All in all, VDAC1 can be exploited as a potential prognostic marker and therapeutic target in BC, especially in TNBC.

Pan-Cancer Analysis of Voltage-Dependent Anion Channel (VDAC1) as a Cancer Therapeutic Target or Diagnostic Biomarker

“…), our analysis indicated that high expression of VDAC1 was related to poor OS, RFS, and distant metastasis-free survival (DMFS) of cases, especially in a subgroup analysis of "TP53 wild type," "PR negative," "HER2 negative," "grade 3," "Intrinsic subtype/Luminal A," "Pietenpol subtype/Basal-like 2," and "Pietenpol subtype/Mesenchymal stem-like" (Supplementary Figure 2b and Supplementary Table 1). Similarly, it has been reported that VDAC1 is highly expressed in breast cancer tissues, which may predict the poor prognosis of breast cancer cases, especially triple-negative breast cancer [34]. In addition, the results in vitro and mouse models indicated that silencing VDAC1 expression inhibited the growth of different cancer cells, including triple-negative breast cancer, suggesting VDAC1 was involved in the reprogramming of breast cancer cells metabolism, regardless of origin or mutational status [35].…”

Pro-apoptotic and anti-invasive properties underscore the tumor suppressing impact of myoglobin on subset of human breast cancer cells

“…VDAC1, despite its role in mitochondrial metabolism [65], acts as a suppressor of apoptosis by downregulating caspases, p53, cytochrome c and growth in cancer cells [66] and yeast [67]. Recently, VDAC1 expression was correlated with poor prognosis in human breast cancer patients [68]. The loss of MB in normoxic MCF7 cells, however, not only reduces apoptosis, but may, in parallel, increase autophagy to eventually increase longevity of mammary carcinoma, and perhaps many cancers cell types [69][70][71], yet to be further studied and verified.…”

The Application of Nucleic Acid Probe–Based Fluorescent Sensing and Imaging in Cancer Diagnosis and Therapy

“…Protein also exerts enormous functions in diverse pathological activities, which provides effective targets for cancer diagnosis. For example, cytochrome c (Cyt c), a heme protein, is a significant biomarker for apoptosis ( Chen et al, 2021 ). Cyt c–specific nucleic acid aptamers have the strong binding affinity to Cyt c. The detection of Cyt c relies on the interaction of nucleic acid aptamers with fluorescent CDs.…”