Main Article Content
Abstract
Highlights:
1. In this study, new primers designed using the semi-nested polymerase chain reaction (PCR) method were utilized to identify MAGE-A11 and MAGE-A12 expressions in specimens collected from core biopsy, forcep biopsy, and bronchoalveolar lavage.
2. The histopathological analysis revealed positive expressions of MAGE-A11 and MAGE-A12 in specimens diagnosed with non-small cell lung cancer (NSCLC) as well as in specimens with no malignant cells.
3. This study provides evidence indicating that the detection of messenger ribonucleic acid (mRNA) of MAGE-A11 and MAGE-A12 by nested reverse transcription PCR can improve the accuracy of lung cancer diagnosis.
Abstract
The melanoma antigen gene (MAGE) belongs to the group of cancer-testis antigens that are exclusively expressed in germ cells but may be re-expressed in cancer cells. The highly expressed MAGE-A subfamily in lung cancer may potentially be a diagnostic and prognostic biomarker. This study aimed to identify MAGE-A11 and MAGE-A12 expressions in lung tumors obtained from core biopsy, forceps biopsy, and bronchoalveolar lavage specimens. A cross-sectional observational study was conducted on 90 patients clinically diagnosed with lung tumors. These patients received core biopsy, forceps biopsy, and bronchoalveolar lavage interventions after ethical approval was obtained. The complementary deoxyribonucleic acid (cDNA) quality was assessed by the polymerase chain reaction (PCR) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The assessment was performed to ascertain if all specimens exhibited positive PCR amplification of the GAPDH gene. MAGE-A11 and MAGE-A12 were identified through a semi-nested reverse transcription PCR. The positive results were detected by measuring the PCR products, with MAGE-A11 and MAGE-A12 at base pairs (bp) of 858 and 496 in the first and second rounds, respectively. The expressions of MAGE-A11 and MAGE-A12 were observed in 3 (3.33%) and 40 (44.44%) out of 90 specimens, respectively. The prevalence rate of non-small cell lung cancer (NSCLC) was 31.11% (28/90). Among these cases, 3.57% (1/28) showed the expression of MAGE-A11, while 32.14% (9/28) exhibited the expression of MAGE-A12. Sixty-two (68.89%) out of 90 patients were diagnosed with no tumor cell malignancy. Out of 62 cases, 2 (3.23%) exhibited the expression of MAGE-A11, while 31 (50%) demonstrated the expression of MAGE-A12. MAGE-A11 and MAGE-A12 were detected in NSCLC and certain specimens with a pathological diagnosis that indicated the absence of malignant cells. In conclusion, MAGE A11 and MAGE A12 have potential markers to improve the pathological diagnosis of lung cancer. Further investigation is necessary to explore the expression of MAGE-A in correlation with lung cancer progression.
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References
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- Brisam M, Rauthe S, Hartmann S, et al (2016). Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma. Oncol Rep 35, 1979-86 (doi: https://doi.org/10.3892/or.2016.4600 )
- Cainap C, Pop LA, Balacescu O, et al (2021). Early diagnosis and screening for lung cancer. Cold Spring Harb Perspect Med 10, 1993-2009 (PMID: 32774997)
- Engeland K (2022). Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ 29, 946-60 (doi: https://doi.org/10.1038/s41418-022-00988-z )
- Ferlay J, Ervik M, Lam F, et al (2020). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today , accessed [12 September 2023]
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- Jia S, Zhang M, Li Y, et al (2020). MAGE-A11 Expression Predicts Patient Prognosis in Head and Neck Squamous Cell Carcinoma. Cancer Manag Res 12, 1427-35 (doi: https://doi.org/10.2147/CMAR.S237867 )
- Lee HS, Kim SW, Hong JC, et al (2013) Expression of MAGE A1-6 and the clinical characteristics of papillary thyroid carcinoma. Anticancer Res 33, 1731-6 (PMID: 23564824)
- Li R, Gong J, Xiao C, et al (2020). A comprehensive analysis of the MAGE family as prognostic and diagnostic markers for hepatocellular carcinoma. Genomics 112, 5101-14 (doi: https://doi.org/10.1016/j.ygeno.2020.09.026 )
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- Liu S, Zhao Y, Xu Y, et al (2020) Mage-A genes as predictors of the outcome of laryngeal squamous cell carcinoma. Oncol Lett 20, 1-10 (doi: https://doi.org/10.3892/ol.2020.11920 )
- Malhotra J, Malvezzi M, Negri E, et al (2016). Risk factors for lung cancer worldwide. Eur Respir J 48, 889-902 (doi: https://doi.org/10.1183/13993003.00359-2016 )
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- Mohsenzadegan M, Razmi M, Vafaei S, et al (2022). Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer. Sci Rep 12, 599 (doi: https://doi.org/10.1038/s41598-021-04510-2 )
- Ning J, Ge T, Jiang M, et al (2021). Early diagnosis of lung cancer: which is the optimal choice? Aging (Albany NY) 13, 6214-27 (doi: https://doi.org/10.18632/aging.202504 )
- í•unap K, Kurg K, Víµsa L, et al (2018). Antibody response against cancer-testis antigens MAGEA4 and MAGEA10 in patients with melanoma. Oncol Lett 16, 211-8 (doi: https://doi.org/10.3892/ol.2018.8684 )
- Poojary M, Jishnu PV, Kabekkodu SP (2020). Prognostic Value of Melanoma-Associated Antigen-A (MAGE-A) Gene Expression in Various Human Cancers: A Systematic Review and Meta-analysis of 7428 Patients and 44 Studies. Mol Diagn Ther 24, 537-55 (doi: https://doi.org/10.1007/s40291-020-00476-5 )
- Sang M, Gu L, Yin D, et al (2017). MAGE-A family expression is correlated with poor survival of patients with lung adenocarcinoma: a retrospective clinical study based on tissue microarray. J Clin Pathol 70, 533-40 (doi: https://doi.org/10.1136/jclinpath-2016-203718 )
- Siegel RL, Miller KD, Wagle NS, et al (2023). Cancer statistics, 2023. CA Cancer J Clin 73, 17-48 (doi: https://doi.org/10.3322/caac.21763 )
- Su S, Minges JT, Grossman G, et al (2013). Proto-oncogene activity of melanoma antigen-A11 (MAGE-A11) regulates retinoblastoma-related p107 and E2F1 proteins. J Biol Chem 288, 24809-24 (doi: https://doi.org/10.1074/jbc.M113.468579 )
- Sung H, Ferlay J, Siegel RL, et al (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71, 209-49 (doi: https://doi.org/10.3322/caac.21660 )
- Weon JL, Potts PR (2015). The MAGE protein family and cancer. Curr Opin Cell Biol 37, 1-8 (doi: https://doi.org/10.1016/j.ceb.2015.08.002 )
- Wu J, Wang J, Shen W (2017). Identification of MAGEA12 as a prognostic outlier gene in gastric cancers. Neoplasma 64, 238-43 (doi: https://doi.org/10.4149/neo_2017_210 )
- Yanagi T, Nagai K, Shimizu H, et al (2017). Melanoma antigen A12 regulates cell cycle via tumor suppressor p21 expression. Oncotarget 8, 68448-59 (doi: https://doi.org/10.18632/oncotarget.19497 )
- Yi E, Chang JE, Leem C, et al (2017). Association of MAGE A1-6 Expression with Lung Cancer Progression. J Cancer 8, 1324-9 (doi: https://doi.org/10.7150/jca.18086 )
- Zhao G, Bae JY, Zheng Z, et al (2019). Overexpression and Implications of Melanoma-associated Antigen A12 in Pathogenesis of Human Cutaneous Squamous Cell Carcinoma. Anticancer Res 39, 1849-57 (doi: https://doi.org/10.21873/anticanres.13292 )
References
Almutairi MH, Alotaibi MM, Alonaizan R, et al (2022). Identification of MAGE-A family genes in colon cancer patients and their expression mechanism. J King Saud Univ-Sci 34, 102251 (doi: https://doi.org/10.1016/j.jksus.2022.102251)
Brisam M, Rauthe S, Hartmann S, et al (2016). Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma. Oncol Rep 35, 1979-86 (doi: https://doi.org/10.3892/or.2016.4600 )
Cainap C, Pop LA, Balacescu O, et al (2021). Early diagnosis and screening for lung cancer. Cold Spring Harb Perspect Med 10, 1993-2009 (PMID: 32774997)
Engeland K (2022). Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ 29, 946-60 (doi: https://doi.org/10.1038/s41418-022-00988-z )
Ferlay J, Ervik M, Lam F, et al (2020). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today , accessed [12 September 2023]
Goel S, Yeshvanth SK, Asnani R, et al (2022). Accuracy of bronchial cytological diagnosis in lung lesions in comparison with histopathology. J Cytol 39, 163-8 (doi: https://doi.org/10.4103/joc.joc_44_22 )
Gu L, Sang M, Yin D, et al (2018). MAGE-A gene expression in peripheral blood serves as a poor prognostic marker for patients with lung cancer. Thorac Cancer 9, 431-8 (doi: https://doi.org/10.1111/1759-7714.12571 )
Hou SY, Sang MX, Geng CZ, et al (2014). Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression mechanism. Arch Med Res 45, 44-51 (doi: http://doi.org/10.1016/j.arcmed.2013.10.005)
James SR, Cedeno CD, Sharma A, et al (2013). DNA methylation and nucleosome occupancy regulate the cancer germline antigen gene MAGEA11. Epigenetics 8, 849-63 (doi: https://doi.org/10.4161/epi.25500 )
Jia S, Zhang M, Li Y, et al (2020). MAGE-A11 Expression Predicts Patient Prognosis in Head and Neck Squamous Cell Carcinoma. Cancer Manag Res 12, 1427-35 (doi: https://doi.org/10.2147/CMAR.S237867 )
Lee HS, Kim SW, Hong JC, et al (2013) Expression of MAGE A1-6 and the clinical characteristics of papillary thyroid carcinoma. Anticancer Res 33, 1731-6 (PMID: 23564824)
Li R, Gong J, Xiao C, et al (2020). A comprehensive analysis of the MAGE family as prognostic and diagnostic markers for hepatocellular carcinoma. Genomics 112, 5101-14 (doi: https://doi.org/10.1016/j.ygeno.2020.09.026 )
Lian Y, Sang M, Ding C, et al (2012). Expressions of MAGE-A10 and MAGE-A11 in breast cancers and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol 138, 519-27 (doi: https://doi.org/10.1007/s00432-011-1122-x )
Lian Y, Meng L, Ding P, et al (2018). Epigenetic regulation of MAGE family in human cancer progression-DNA methylation, histone modification, and non-coding RNAs. Clin Epigenet 10, 115 (doi: https://doi.org/10.1186/s13148-018-0550-8 )
Liu S, Zhao Y, Xu Y, et al (2020) Mage-A genes as predictors of the outcome of laryngeal squamous cell carcinoma. Oncol Lett 20, 1-10 (doi: https://doi.org/10.3892/ol.2020.11920 )
Malhotra J, Malvezzi M, Negri E, et al (2016). Risk factors for lung cancer worldwide. Eur Respir J 48, 889-902 (doi: https://doi.org/10.1183/13993003.00359-2016 )
Marhana IA, Widianiti K, Kusumastuti EH (2022). Conformity of fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) in peripheral lung tumor patients: a cross-sectional study. Ann Med Surg 75, 103423 (doi: https://doi.org/10.1016/j.amsu.2022.103423 )
Mastutik G, Rahniayu A, Marhana IA, et al (2021). Novel universal primers to identify the expression of MAGE A1-A10 in the core biopsy of lung cancer. Middle East J Cancer 12, 10-9 (doi: https://doi.org/10.30476/mejc.2020.82457.1089)
Mastutik G, Rahniayu A, Marhana IA, et al (2023). The MAGE A1-A10 Expression associated with Histopathological Findings of Malignant or Non-Malignant Cells in Peripheral Lung Tumors. Asian Pac J Cancer Prev 24, 2329-35 (doi: https://doi.org/10.31557/APJCP.2023.24.7.2329 )
Mohsenzadegan M, Razmi M, Vafaei S, et al (2022). Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer. Sci Rep 12, 599 (doi: https://doi.org/10.1038/s41598-021-04510-2 )
Ning J, Ge T, Jiang M, et al (2021). Early diagnosis of lung cancer: which is the optimal choice? Aging (Albany NY) 13, 6214-27 (doi: https://doi.org/10.18632/aging.202504 )
í•unap K, Kurg K, Víµsa L, et al (2018). Antibody response against cancer-testis antigens MAGEA4 and MAGEA10 in patients with melanoma. Oncol Lett 16, 211-8 (doi: https://doi.org/10.3892/ol.2018.8684 )
Poojary M, Jishnu PV, Kabekkodu SP (2020). Prognostic Value of Melanoma-Associated Antigen-A (MAGE-A) Gene Expression in Various Human Cancers: A Systematic Review and Meta-analysis of 7428 Patients and 44 Studies. Mol Diagn Ther 24, 537-55 (doi: https://doi.org/10.1007/s40291-020-00476-5 )
Sang M, Gu L, Yin D, et al (2017). MAGE-A family expression is correlated with poor survival of patients with lung adenocarcinoma: a retrospective clinical study based on tissue microarray. J Clin Pathol 70, 533-40 (doi: https://doi.org/10.1136/jclinpath-2016-203718 )
Siegel RL, Miller KD, Wagle NS, et al (2023). Cancer statistics, 2023. CA Cancer J Clin 73, 17-48 (doi: https://doi.org/10.3322/caac.21763 )
Su S, Minges JT, Grossman G, et al (2013). Proto-oncogene activity of melanoma antigen-A11 (MAGE-A11) regulates retinoblastoma-related p107 and E2F1 proteins. J Biol Chem 288, 24809-24 (doi: https://doi.org/10.1074/jbc.M113.468579 )
Sung H, Ferlay J, Siegel RL, et al (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71, 209-49 (doi: https://doi.org/10.3322/caac.21660 )
Weon JL, Potts PR (2015). The MAGE protein family and cancer. Curr Opin Cell Biol 37, 1-8 (doi: https://doi.org/10.1016/j.ceb.2015.08.002 )
Wu J, Wang J, Shen W (2017). Identification of MAGEA12 as a prognostic outlier gene in gastric cancers. Neoplasma 64, 238-43 (doi: https://doi.org/10.4149/neo_2017_210 )
Yanagi T, Nagai K, Shimizu H, et al (2017). Melanoma antigen A12 regulates cell cycle via tumor suppressor p21 expression. Oncotarget 8, 68448-59 (doi: https://doi.org/10.18632/oncotarget.19497 )
Yi E, Chang JE, Leem C, et al (2017). Association of MAGE A1-6 Expression with Lung Cancer Progression. J Cancer 8, 1324-9 (doi: https://doi.org/10.7150/jca.18086 )
Zhao G, Bae JY, Zheng Z, et al (2019). Overexpression and Implications of Melanoma-associated Antigen A12 in Pathogenesis of Human Cutaneous Squamous Cell Carcinoma. Anticancer Res 39, 1849-57 (doi: https://doi.org/10.21873/anticanres.13292 )