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Published in: Diagnostic Pathology 1/2021

Open Access 01-12-2021 | Esophageal Cancer | Research

MAEL as a diagnostic marker for the early detection of esophageal squamous cell carcinoma

Authors: Mohammad Reza Abbaszadegan, Negin Taghehchian, Azadeh Aarabi, Faride Akbari, Ehsan Saburi, Meysam Moghbeli

Published in: Diagnostic Pathology | Issue 1/2021

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Abstract

Background

Esophageal cancer is one of the most common malignancies among Iranians and is categorized as adenocarcinoma and squamous cell carcinoma. Various environmental and genetic factors are involved in this malignancy. Despite the recent advances in therapeutic modalities there is still a noticeable mortality rate among such patients which can be related to the late diagnosis. Regarding high ratio of esophageal squamous cell carcinoma (ESCC) in Iran, therefore it is required to assess molecular biology of ESCC to introduce novel diagnostic markers. In present study we assessed the role of Maelstrom (MAEL) cancer testis gene in biology of ESCC among Iranian patients.

Methods

Forty-five freshly normal and tumor tissues were enrolled to evaluate the levels of MAEL mRNA expression using Real time polymerase chain reaction.

Results

MAEL under and over expressions were observed in 12 (26.7%) and 9 (20%) of patients, respectively. MAEL fold changes were ranged between -4.33 to -1.87 (mean SD: -2.90± 0.24) and 1.92 to 7.72 (mean SD: 3.97± 0.69) in under and over expressed cases, respectively. There was a significant association between stage and MAEL expression in which majority of MAEL over expressed tumors (8/9, 88.9%) were in stage I/II (p<0.001). There was also a significant correlation between MAEL expression and depth of invasion in which tumor with T1/2 had higher levels of MAEL expression compared with T3/4 tumors (p=0.017). Moreover, there were significant correlations between MAEL expression, tumor size (p=0.028), and grade (p=0.003) among male patients.

Conclusions

Our data showed that the MAEL was mainly involved in primary stages of tumor progression and it has a declining expression levels toward the advanced stages and higher depth of tumor invasions. Therefore, MAEL can be efficiently introduced as an early detection marker among Iranian ESCC patients.
Literature
1.
go back to reference Sadjadi A, et al. Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J Cancer Prev. 2005;6(3):359–63.PubMed Sadjadi A, et al. Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J Cancer Prev. 2005;6(3):359–63.PubMed
2.
go back to reference Sadjadi A, et al. Cancer occurrence in Ardabil: results of a population-based cancer registry from Iran. Int J Cancer. 2003;107(1):113–8.PubMedCrossRef Sadjadi A, et al. Cancer occurrence in Ardabil: results of a population-based cancer registry from Iran. Int J Cancer. 2003;107(1):113–8.PubMedCrossRef
3.
go back to reference Gholipour M, et al. Esophageal Cancer in Golestan Province, Iran: A Review of Genetic Susceptibility and Environmental Risk Factors. Middle East J Dig Dis. 2016;8(4):249–66.PubMedPubMedCentralCrossRef Gholipour M, et al. Esophageal Cancer in Golestan Province, Iran: A Review of Genetic Susceptibility and Environmental Risk Factors. Middle East J Dig Dis. 2016;8(4):249–66.PubMedPubMedCentralCrossRef
4.
go back to reference Abbaszadegan MR, et al. WNT and NOTCH signaling pathways as activators for epidermal growth factor receptor in esophageal squamous cell carcinoma. Cell Mol Biol Lett. 2018;23:42.PubMedPubMedCentralCrossRef Abbaszadegan MR, et al. WNT and NOTCH signaling pathways as activators for epidermal growth factor receptor in esophageal squamous cell carcinoma. Cell Mol Biol Lett. 2018;23:42.PubMedPubMedCentralCrossRef
6.
go back to reference Moghbeli M, et al. Correlation Between Meis1 and Msi1 in Esophageal Squamous Cell Carcinoma. J Gastrointest Cancer. 2016;47(3):273–7.PubMedCrossRef Moghbeli M, et al. Correlation Between Meis1 and Msi1 in Esophageal Squamous Cell Carcinoma. J Gastrointest Cancer. 2016;47(3):273–7.PubMedCrossRef
7.
8.
go back to reference Ferlay J, et al. Cancer incidence and mortality worldwide. Lyon: International Agency for Research on Cancer; 2010. Ferlay J, et al. Cancer incidence and mortality worldwide. Lyon: International Agency for Research on Cancer; 2010.
9.
10.
go back to reference Abbaszadegan MR, Moghbeli M. Role of MAML1 and MEIS1 in Esophageal Squamous Cell Carcinoma Depth of Invasion. Pathol Oncol Res. 2018;24(2):245–50.PubMedCrossRef Abbaszadegan MR, Moghbeli M. Role of MAML1 and MEIS1 in Esophageal Squamous Cell Carcinoma Depth of Invasion. Pathol Oncol Res. 2018;24(2):245–50.PubMedCrossRef
11.
12.
go back to reference Abbaszadegan MR, et al. MAEL Cancer-Testis Antigen as a Diagnostic Marker in Primary Stages of Gastric Cancer with Helicobacter pylori Infection. Journal of Gastrointestinal Cancer. 2020;51(1):17–22.PubMedCrossRef Abbaszadegan MR, et al. MAEL Cancer-Testis Antigen as a Diagnostic Marker in Primary Stages of Gastric Cancer with Helicobacter pylori Infection. Journal of Gastrointestinal Cancer. 2020;51(1):17–22.PubMedCrossRef
13.
go back to reference Li Y, et al. Roles of cancer/testis antigens (CTAs) in breast cancer. Cancer letters. 2017;399:64–73.PubMedCrossRef Li Y, et al. Roles of cancer/testis antigens (CTAs) in breast cancer. Cancer letters. 2017;399:64–73.PubMedCrossRef
14.
go back to reference Grizzi F, et al. Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma. J Transl Med. 2007;5:3.PubMedPubMedCentralCrossRef Grizzi F, et al. Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma. J Transl Med. 2007;5:3.PubMedPubMedCentralCrossRef
15.
go back to reference Xiao L, et al. Identification of a novel human cancer/testis gene MAEL that is regulated by DNA methylation. Mol Biol Rep. 2010;37(5):2355–60.PubMedCrossRef Xiao L, et al. Identification of a novel human cancer/testis gene MAEL that is regulated by DNA methylation. Mol Biol Rep. 2010;37(5):2355–60.PubMedCrossRef
16.
go back to reference Li Q, et al. MAEL expression links epithelial-mesenchymal transition and stem cell properties in colorectal cancer. Int J Cancer. 2016;139(11):2502–11.PubMedCrossRef Li Q, et al. MAEL expression links epithelial-mesenchymal transition and stem cell properties in colorectal cancer. Int J Cancer. 2016;139(11):2502–11.PubMedCrossRef
17.
go back to reference Sato K, Siomi MC. Functional and structural insights into the piRNA factor Maelstrom. FEBS Lett. 2015;589(14):1688–93.PubMedCrossRef Sato K, Siomi MC. Functional and structural insights into the piRNA factor Maelstrom. FEBS Lett. 2015;589(14):1688–93.PubMedCrossRef
19.
go back to reference Cox DN, Chao A, Lin H. piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development. 2000;127(3):503–14.PubMedCrossRef Cox DN, Chao A, Lin H. piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development. 2000;127(3):503–14.PubMedCrossRef
20.
go back to reference Janic A, et al. Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science. 2010;330(6012):1824–7.PubMedCrossRef Janic A, et al. Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science. 2010;330(6012):1824–7.PubMedCrossRef
21.
go back to reference Lee JH, et al. Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum Mol Genet. 2006;15(2):201–11.PubMedCrossRef Lee JH, et al. Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum Mol Genet. 2006;15(2):201–11.PubMedCrossRef
22.
go back to reference Qiao D, et al. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002;21(25):3988–99.PubMedCrossRef Qiao D, et al. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 2002;21(25):3988–99.PubMedCrossRef
23.
go back to reference Taubert H, et al. Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma. Oncogene. 2007;26(7):1098–100.PubMedCrossRef Taubert H, et al. Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma. Oncogene. 2007;26(7):1098–100.PubMedCrossRef
24.
go back to reference Soper SF, et al. Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis. Dev Cell. 2008;15(2):285–97.PubMedPubMedCentralCrossRef Soper SF, et al. Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis. Dev Cell. 2008;15(2):285–97.PubMedPubMedCentralCrossRef
25.
go back to reference Kim YH, et al. Epigenomic analysis of aberrantly methylated genes in colorectal cancer identifies genes commonly affected by epigenetic alterations. Ann Surg Oncol. 2011;18(8):2338–47.PubMedPubMedCentralCrossRef Kim YH, et al. Epigenomic analysis of aberrantly methylated genes in colorectal cancer identifies genes commonly affected by epigenetic alterations. Ann Surg Oncol. 2011;18(8):2338–47.PubMedPubMedCentralCrossRef
26.
go back to reference Liu L, et al. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3beta/Snail signaling. Hepatology. 2014;59(2):531–43.PubMedCrossRef Liu L, et al. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3beta/Snail signaling. Hepatology. 2014;59(2):531–43.PubMedCrossRef
27.
go back to reference Li XD, et al. Overexpression of maelstrom promotes bladder urothelial carcinoma cell aggressiveness by epigenetically downregulating MTSS1 through DNMT3B. Oncogene. 2016;35(49):6281–92.PubMedCrossRef Li XD, et al. Overexpression of maelstrom promotes bladder urothelial carcinoma cell aggressiveness by epigenetically downregulating MTSS1 through DNMT3B. Oncogene. 2016;35(49):6281–92.PubMedCrossRef
28.
go back to reference Li P, et al. Maelstrom Directs Myeloid-Derived Suppressor Cells to Promote Esophageal Squamous Cell Carcinoma Progression via Activation of the Akt1/RelA/IL8 Signaling Pathway. Cancer Immunol Res. 2018;6(10):1246–59.PubMedCrossRef Li P, et al. Maelstrom Directs Myeloid-Derived Suppressor Cells to Promote Esophageal Squamous Cell Carcinoma Progression via Activation of the Akt1/RelA/IL8 Signaling Pathway. Cancer Immunol Res. 2018;6(10):1246–59.PubMedCrossRef
29.
go back to reference Kim SH, et al. Mael is essential for cancer cell survival and tumorigenesis through protection of genetic integrity. Oncotarget. 2017;8(3):5026–37.PubMedCrossRef Kim SH, et al. Mael is essential for cancer cell survival and tumorigenesis through protection of genetic integrity. Oncotarget. 2017;8(3):5026–37.PubMedCrossRef
30.
go back to reference Yuan L, et al. Proteomic analysis reveals that MAEL, a component of nuage, interacts with stress granule proteins in cancer cells. Oncol Rep. 2014;31(1):342–50.PubMedCrossRef Yuan L, et al. Proteomic analysis reveals that MAEL, a component of nuage, interacts with stress granule proteins in cancer cells. Oncol Rep. 2014;31(1):342–50.PubMedCrossRef
32.
go back to reference Pek JW, Lim AK, Kai T. Drosophila maelstrom ensures proper germline stem cell lineage differentiation by repressing microRNA-7. Dev Cell. 2009;17(3):417–24.PubMedCrossRef Pek JW, Lim AK, Kai T. Drosophila maelstrom ensures proper germline stem cell lineage differentiation by repressing microRNA-7. Dev Cell. 2009;17(3):417–24.PubMedCrossRef
33.
go back to reference Frederick L, et al., AJCC cancer staging manual. 2002: Springer Science & Business Media. Frederick L, et al., AJCC cancer staging manual. 2002: Springer Science & Business Media.
34.
go back to reference Abbaszadegan MR, et al., MAEL Cancer-Testis Antigen as a Diagnostic Marker in Primary Stages of Gastric Cancer with Helicobacter pylori Infection. J Gastrointest Cancer, 2018. Abbaszadegan MR, et al., MAEL Cancer-Testis Antigen as a Diagnostic Marker in Primary Stages of Gastric Cancer with Helicobacter pylori Infection. J Gastrointest Cancer, 2018.
35.
go back to reference Hosono M, et al. CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells. Oncotarget. 2017;8(62):106071–88.PubMedPubMedCentralCrossRef Hosono M, et al. CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells. Oncotarget. 2017;8(62):106071–88.PubMedPubMedCentralCrossRef
36.
go back to reference Anderson P, Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem Sci. 2008;33(3):141–50.PubMedCrossRef Anderson P, Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem Sci. 2008;33(3):141–50.PubMedCrossRef
37.
go back to reference Decker CJ, Parker R. P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. Cold Spring Harb Perspect Biol. 2012;4(9):a012286.PubMedPubMedCentralCrossRef Decker CJ, Parker R. P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. Cold Spring Harb Perspect Biol. 2012;4(9):a012286.PubMedPubMedCentralCrossRef
38.
39.
go back to reference Pek JW, Patil VS, Kai T. piRNA pathway and the potential processing site, the nuage, in the Drosophila germline. Dev Growth Differ. 2012;54(1):66–77.PubMedCrossRef Pek JW, Patil VS, Kai T. piRNA pathway and the potential processing site, the nuage, in the Drosophila germline. Dev Growth Differ. 2012;54(1):66–77.PubMedCrossRef
40.
go back to reference Anderson P, Kedersha N. RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol. 2009;10(6):430–6.PubMedCrossRef Anderson P, Kedersha N. RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol. 2009;10(6):430–6.PubMedCrossRef
41.
go back to reference Costa Y, et al. Mouse MAELSTROM: the link between meiotic silencing of unsynapsed chromatin and microRNA pathway? Hum Mol Genet. 2006;15(15):2324–34.PubMedCrossRef Costa Y, et al. Mouse MAELSTROM: the link between meiotic silencing of unsynapsed chromatin and microRNA pathway? Hum Mol Genet. 2006;15(15):2324–34.PubMedCrossRef
43.
go back to reference Gloushankova N, Zhitnyak I, Rubtsova S. Role of epithelial-mesenchymal transition in tumor progression. Biochemistry. 2018;83(12–13):1469–76.PubMed Gloushankova N, Zhitnyak I, Rubtsova S. Role of epithelial-mesenchymal transition in tumor progression. Biochemistry. 2018;83(12–13):1469–76.PubMed
44.
go back to reference Fang Y, et al. MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma. Hepatology. 2012;55(6):1852–62.PubMedCrossRef Fang Y, et al. MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma. Hepatology. 2012;55(6):1852–62.PubMedCrossRef
45.
go back to reference Lyons RM, Keski-Oja J, Moses HL. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol. 1988;106(5):1659–65.PubMedCrossRef Lyons RM, Keski-Oja J, Moses HL. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol. 1988;106(5):1659–65.PubMedCrossRef
Metadata
Title
MAEL as a diagnostic marker for the early detection of esophageal squamous cell carcinoma
Authors
Mohammad Reza Abbaszadegan
Negin Taghehchian
Azadeh Aarabi
Faride Akbari
Ehsan Saburi
Meysam Moghbeli
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2021
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-021-01098-z

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