Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

Abstract

Purpose An early and accurate diagnosis of ovarian carcinoma (OC) may reduce morbidity and mortality of the patients. To improve the clinical outcome in OC patients, the present study is aimed at identifying robust biomarkers for early OC diagnosis. Experimental Design In order to look for early‐stage protein markers, a systematic protein profiling approach involving 2‐dimensional electrophoresis coupled with mass spectrometric analyses of human malignant and non‐malignant ovarian biopsy samples, is performed. Results Six 2D gel spots, corresponding to five proteins, display statistically significant differential expression in the tumor tissues compared to benign controls (FDR ≤ 0.05; PMF score ≥ 79). Ingenuity pathway analysis predicts two proteins, that is, Ca2+‐dependent membrane‐binding protein annexin A6 (AnxA6) and the metabolic enzyme l‐lactate dehydrogenase A chain, as potential predictive biomarkers. Increased expression of AnxA6 is further ascertained by Western blot and enzyme linked immunosorbent assay in the resected tissues and the plasma samples. The expression is found markedly increasing particularly in the advanced stage tumors. Conclusions and Clinical Relevance The significant upregulation of AnxA6 in OC, reported for the first time, is likely to provide insight into the mechanism of OC progression, which may lead to the design of potential diagnostic and therapeutic strategies.

ANXA6 Contributes to Radioresistance by Promoting Autophagy via Inhibiting the PI3K/AKT/mTOR Signaling Pathway in Nasopharyngeal Carcinoma

“…Thus, a total of 29 genes were identified from NPC cells and clinical specimens and are visualized by heat map in Figure 1D, including eight co-upregulated genes and six co-downregulated genes. We speculated that the high expression of ANXA6 among them was probably an important prognostic marker of NPC radioresistance because the elevation of ANXA6 has been previously reported to be an independent risk factor for poor prognosis of many neoplasms, such as cervix carcinogenesis, pancreatic cancer, ovarian carcinoma, and thyroid cancer (Lomnytska et al, 2011;O'Sullivan et al, 2017;Lee et al, 2018;Noreen et al, 2019).…”

Tubulin Beta 2C Chain (TBB2C), a Potential Marker of Ovarian Cancer, an Insight from Ovarian Cancer Proteome Profile

“…Protein fractionation by 2D-GE was performed as previously described. 16 Briefly, the tissue lysate containing ∼800 μg of proteins was mixed in rehydration buffer and applied to 17 cm linear IpG strips (pH 3–10) (Serva, Heidelberg, Germany), followed by passive rehydration and isoelectric focusing (IEF) on a PROTEAN i12 IEF cell (Bio-Rad) for a total of 60 kVhr at 20 °C. Following IEF, IpG strips were equilibrated in equilibration buffers and analyzed by two-dimensional SDS-PAGE.…”

“…In our previous study, 16 by employing 2-DE and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) analysis, we compared the proteome maps of the OC and benign disease control ovarian tissues to identify differentially represented proteins that can serve as putative biomarkers of the disease. Resultantly, we reported annexin A6, a potential indicator of OC.…”

Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance

“…Tumor promotor breast cancer [246], cervical cancer [251], esophageal cancer [252], melanoma [252], ovarian cancer [253], pancreatic cancer [254][255][256], women's thyroid cancer [257] Tumor suppressor A431 epithelial carcinoma [240][241][242]245], breast cancer (TNBC, EGFR overexpressing and ER-negative) [239][240][241]246], cervical cancer [249], gastric cancer [248], HCC [250] Chemotherapy response TNBC [239,247,258], gastric cancer [259] On the other hand, tumor promoter activities of AnxA6 have also been reported, with AnxA6 displaying pro-invasive functions in invasive breast cancer cells [239,246]. In gastric cancer, AnxA6 conferred drug resistance via β1 integrin and FAK activation [259].…”