Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value

Lomnytska, Marta; Becker, Susanne; Bodin, Inger; Olsson, Anna; Hellman, Kristina; Hellström, Ann‐Cathrin; Mints, Miriam; Hellman, Ulf; Auer, Gert; Andersson, Sonia

doi:10.1038/sj.bjc.6605992

Cited by 57 publications

(57 citation statements)

References 42 publications

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“…To our knowledge, this is the first study to evaluate HSPB1 expression in human bronchial epithelium carcinogenic process and its early diagnostic significance in LSCC. Interestingly, previous studies have showed that HSPB1 was overexpressed in preneoplastic lesions in the uterine cervix and gastric cancer, and has an early diagnostic significance for these two tumors (56,57), which also supports HSPB1 as biomarker for early detection of LSCC. It has been reported that HSPB1 overexpression was involved in liver carcinogenesis induced by chemical carcinogens (58), and HSPB1 expression in benign proliferating breast lesions increased risk of cell malignant progression (59).…”

Section: Knockdown Of Gstp1 Increased the Susceptibility Of Human Bromentioning

confidence: 83%

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Zeng

Zhang

Deng

et al. 2012

Molecular & Cellular Proteomics

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To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffinembedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplatic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo ( Lung cancer is the most frequently occurring malignancy with increasing incidence and is the leading cause of mortality in cancer-related deaths in China and worldwide (1, 2). Although great improvement has been made in diagnosis and treatment of lung cancer, the overall patients' survival is still very low and does not exceed 15% (3). The poor prognosis of this cancer is mainly explained by the fact that the diagnosis is generally made only at advanced stages because of the lack of reliable, early diagnostic biomarkers and the limited understanding of its carcinogenic mechanisms. Therefore, identification of biomarkers for early detection of lung cancer is mandatory, in turn leading to more effective treatment and reduction of mortality.Lung squamous cell carcinoma (LSCC) 1 originated from the bronchial epithelial cells is the most common histological type of lung cancer. It is known that carcinogenesis of LSCC is a multistage process and the result of multistep accumulation of genetic and epigenetic alterations (4). With exposure to environmental carcinogens, bronchial epithelial carcinogenesis often progresses in the following manner: hyperplasia, squamous metaplasia (SM), atypical hyperplasia (AH), cancer in situ (CIS) and invasive cancer (5). LSCC is the end-point of a whole range of morphological abnormalities that are dis-...

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Section: Knockdown Of Gstp1 Increased the Susceptibility Of Human Bromentioning

confidence: 83%

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Zeng

Zhang

Deng

et al. 2012

Molecular & Cellular Proteomics

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“…+ cells among atypical cells increased from CIN2/3 to invasive SCC (40). Based on these results, it is possible to hypothesize that the detectable alterations in the protein expression levels of AnxA6 in SCC precursor lesions may aid in the cytological and pathological diagnostics of CC and its prognostic evaluation.…”

Section: Roles Of Anxa6 In Cervical Cancer Progression and Malignancymentioning

confidence: 92%

“…In addition, strong expression of AnxA6 was observed in the nucleus of SCC cells, compared with the weak or moderate expression observed in the cytoplasm of SCE cells (25). However, these may be infiltrating immune cells, since their histopathological appearance was observed to be variable (40). Another study by Lomnytska et al (40) indicated that AnxA6 may aid cytology-based diagnostics of SCC precursor lesions, since its expression levels vary during the different sequential steps of SCC carcinogenesis.…”

Section: Roles Of Anxa6 In Cervical Cancer Progression and Malignancymentioning

confidence: 99%

“…A number of studies have demonstrated that AnxA6 is associated with the progression and malignancy of CC, and it is a potential protein marker for SCC development (25,40). Proteomic results of Lomnytska et al (25) demonstrated that AnxA6 was overexpressed in SCC, and the N-terminus of AnxA6 was upregulated 2-fold in SCC compared with cervical mucosa (CM).…”

Section: Roles Of Anxa6 In Cervical Cancer Progression and Malignancymentioning

confidence: 99%

“…However, these may be infiltrating immune cells, since their histopathological appearance was observed to be variable (40). Another study by Lomnytska et al (40) indicated that AnxA6 may aid cytology-based diagnostics of SCC precursor lesions, since its expression levels vary during the different sequential steps of SCC carcinogenesis. Their IHC analysis demonstrated the following findings: i) AnxA6 was preferentially expressed in the cytoplasm of SCC cells vs. the cell membranes of SCE; ii) the cytoplasmic expression of AnxA6 increased during the progression from cervical intraepithelial neoplasia 2/3 (CIN2/3) to microinvasive cancer; iii) invasive SCC displayed the highest sensitivity and specificity during IHC detection of AnxA6, whereas microinvasive SCC presented low expression levels of AnxA6 in the cytoplasm; and iv) the number of sporadic AnxA6…”

Section: Roles Of Anxa6 In Cervical Cancer Progression and Malignancymentioning

confidence: 99%

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Role of annexin A6 in cancer

Liu

Guo

et al. 2015

Oncology Letters

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Abstract. Annexin A6 (AnxA6) is a member of a conserved superfamily of Ca 2+ -dependent membrane-binding annexin proteins. It participates in membrane and cytoskeleton organization, cholesterol homeostasis, membrane trafficking, cell adhesion and signal transduction. The expression levels of AnxA6 are closely associated with melanoma, cervical cancer, epithelial carcinoma, breast cancer, gastric cancer, prostate cancer, acute lymphoblastic leukemia, chronic myeloid leukemia, large-cell lymphoma and myeloma. AnxA6 exhibits dual functions in cancer, acting either as a tumor suppressor or promoter, depending on the type of cancer and the degree of malignancy. In several types of cancer, AnxA6 acts via Ras, Ras/MAPK and/or FAK/PI3K signaling pathways by mainly mediating PKCα, p120GAP, Bcr-Abl and YY1. In the present review, the roles of AnxA6 in different types of cancer are summarized.

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Evaluation of a 4‐protein serum biomarker panel—biglycan, annexin‐A6, myeloperoxidase, and protein S100‐A9 (B‐AMP)—for the detection of esophageal adenocarcinoma

Zaidi

Gopalakrishnan

Kasi

et al. 2014

Cancer

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Objective Esophageal adenocarcinoma (EAC) is associated with a dismal prognosis. The identification of cancer biomarkers advances the possibility for early detection and better monitoring of tumor progression and/or response to therapy. The current study presents results of the development of a serum based four-protein (biglycan, myeloperoxidase, annexin-A6, and protein S100-A9) biomarker-panel for EAC. Design A vertically integrated proteomics-based biomarker discovery approach was used to identify candidate serum biomarkers for detection of EAC. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was performed on FFPE tissue samples that were collected from across the Barrett's esophagus (BE)-EAC disease spectrum. The MS-based spectral count data was used to guide the selection of candidate serum biomarkers. The serum ELISA data was validated in an independent cohort and used to develop a multi-parametric risk assessment model to predict the presence of disease. Results With a minimum threshold of 10 spectral counts, 351 proteins were identified as differentially abundant along the spectrum of BE, HGD and EAC (p < 0.05). Eleven proteins from this dataset were then tested using ELISAs in serum samples of which five proteins were significantly elevated in abundance in the EAC patients compared to normal controls, which mirrored trends across the disease spectrum present in the tissue data. Using serum data a Bayesian Rule Learning predictive model with four biomarkers was developed to accurately classify disease class; the cross-validation results for the merged dataset yielded accuracy of 87% and AUROC of 93 %. Conclusion Serum biomarkers hold significant promise for early non-invasive detection of EAC.

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Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value

Cited by 57 publications

References 42 publications

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Role of annexin A6 in cancer

Evaluation of a 4‐protein serum biomarker panel—biglycan, annexin‐A6, myeloperoxidase, and protein S100‐A9 (B‐AMP)—for the detection of esophageal adenocarcinoma

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