鄭恩加 教授

鄭恩加 (Ann-Joy Cheng)







腫瘤生物學、細胞分子生物學、生物化學 、醫學生物技術









研究方向及研究室特色(Lab & Research Interest)

Research interests

We, Laboratory of Translational Cancer Research are to investigate clinical associated cancer issues, especially on the topic of native Taiwan cancer – Head and neck cancer (HNC). HNC, including oral cavity cancer and pharyngolaryngeal cancer, is one of the ten frequent cancers in the world with an estimated over 500,000 new cases being diagnosed annually. In Taiwan, the incidence of HNC has become the top 5th cancer in male after year of 2006, and is still increasing in recent years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact of family and society. Epidemiologic studies have shown a wide variation range of incidence between worldwide areas. HNC is highly prevalent in Southeast Asia, comprising 30-35% of all malignancies in India, compared to approximately 10% in Taiwan and 2-4% in Western countries. Epidemiologic studies have shown a strong association between HNC and environmental carcinogens, especially the use of tobacco, alcohol, and areca nut. While tobacco smoking is a common habit in Western patients, areca nut chewing inIndia area, the both habits are frequently found In Taiwan patients. Therefore, the differential incidence of HNC may be attributed to certain environmental exposures, in addition to genetic factors.

    According to specific tumor subsite and individual clinical behavior, the treatment of HNC usually integrates with surgery, chemotherapy, and radiotherapy. In order to better serve patients and more comprehensively study this disease, we together with other multidisciplinary investigators and clinical physicians form the Chang Gung Head Neck Oncology Group. The goal of our laboratory is to systemic investigate the molecular carcinogenesis of HNC. The research topics include the carcinogenic mechanism of areca nut, searching of circulating tumor markers, identification of molecular pathogenic networks, and evaluations of prognostic factors. To reach these goals, we have established several HNC cell lines, as well as sublines with the characteristics of highly invasion, radioresistance, chmeoresistance, and chronic area nut exposure. We used advanced techniques, including microarray and bioinformatic analyses to global survey and profile the transcriptomes and proteomes of each specific cellular phenotype. We then used cellular and animal based methods to examine the molecular network pathways and biological functions of the genes that we defined. Finally, we performed clinical association study to evaluate the significance of the identified genes in clinicopathological presentations. Currently, several molecules that were first determined by us demonstrate contributing to HNC, such as DSG3, Grp78, and Gp96. They functions on cellular metastasis, cancer stem cell conversion, and radio-resistance, respectively. We hope the results of our study can contribute to the knowledge in cancer field, as well further apply in clinical diagnosis, therapeutics, and prognosis to benefit medical society.



*Corresponding author

  1. You GR, Chang JT, Li HF, Cheng AJ*. Multifaceted and intricate oncogenic mechanisms of NDRG1 in head and neck cancer depend on its C-terminal 3R-motif. (2022.05) Cells 2022, 11:1581. Doi:10.3390/cells11091581.
  2. Lin CH, Lin CY, Fan KH, Hung SP, Chou YC, Liu CJ, Chou WC, Chen YC, Huang SF, Kang CJ, Chang KP, Wang HM, Cheng AJ, Chang JT. (2021, 12) Efficacy of postoperative unilateral neck irradiation in patients with buccal mucosa squamous carcinoma with extranodal extension: a propensity score analysis. Cancers 2021, 13: 5997. Doi: 10.3390/cancers13235997.
  3. Tang SJ, You GR, Chang JT, Cheng AJ*. (2021.10) Systemic analysis and identification of dysregulated panel lncRNAs contributing to poor prognosis in head-neck cancer. Frontiers Oncol 2021, 11: 731752. Doi: 10.3389/fonc.2021.731752.
  4. Cheng AJ, You GR, Lee CJ, Lu YC, Tang SJ, Huang YF, Huang YC, Lee LY, Fan KS, Chen YC, Huang SF, Chang JT*. (2021.08) Systemic investigation identifying salivary miR-196b as a promising biomarker for early detection of head-neck cancer and oral precancer lesions. Diagnostics 2011, 11: 1411. Doi: 10.3390/diagnostics11081411.
  5. Chen YJ, Chang JT#, You GR, Huang CY, Fan KH, Cheng AJ*. (2021.08) Panel biomarkers associated with cancer invasion and prognostic prediction for head-neck cancer. Biomark Med 2021, 15: 864-877. Doi: 10.2217/bmm-2021-0213.
  6. Chou YC, Fan KH, Lin CY, Hung TM, Huang BS, Chang KP, Kang CJ, Huang SF, Chang PH, Hsu CL, Wang HM, Hsieh JC, Cheng AJ, Chang JT*. (2021.07) Intensity modulated proton beam therapy verse volumetric modulated arc therapy for patients with nasopharyngeal cancer: a propensity score-matched study. Cancers 2021, 13: 3555. Doi: 10.3390/cancers13143555.
  7. You GR, Chang JT#, Li YL, Chen YJ, Huang YC, Fan KH, Chen YC, Kang CJ, Cheng AJ*. Molecular interplays between cell invasion and radio-resistance that lead to poor prognosis in head-neck cancer. (2021.07) Frontiers Oncol 2021, 11: 681717. Doi: 10.3389/fonc.2021.681717.
  8. Fan KH, Yeh CH, Hung SP, Kang CJ, Huang SF, Chang KP, Wang HM, Hsieh JC, Lin CY, Cheng AJ, Ng SH, Chang JT*. (2021.03) Prognostic value of radiologic extranodal extension in patients with hypopharyngeal cancer treated with primary chemoradiation. Radiother Oncol 2021, 156: 217-222. Doi: 10.1016/j.radonc.2020.12.028.
  9. Chen YJ, You GR, Lai MY, Lu LS, Chen CY, Ting LL, Lee HL, Kanno Y, Chiou JF, Cheng AJ*. (2020.11) A combined systemic strategy for overcoming cisplatin resistance in head and neck cancer: from target identification to drug discovery. Cancers 2020, 12: 3482. Doi:10.3390/cancers12113482.
  10. Hung TM, Fan KH, Kang CJ, Huang SF, Lin CY, Ho AT, Wang HM, Hsieh JC, Cheng AJ, Ng SH, Chang JT*. (2020.07) Lymph node-to –primary tumor standardized uptake value ratio on PET predicts distant metastasis in nasopharyngeal carcinoma. Oral Oncol 2020, 110: 104756.Doi: 10.1016/j.oraloncology.2020.104756.
  11. Chen YL, Tsai WH, Ko YC, Lai TY, Cheng AJ, Shiah SG, Hsiao JR, Chang JY, Lin SF. (2020.03) Discoidin Domain Receptor-1 (DDR1) is involved in angiolymphatic invasion in oral cancer. Cancers 2020, 12(4):841. Doi: 10.3390/cancers12040841.
  12. Chiu CC, Yeh TH, Chen RS, Chen HC, Huang YZ, Weng YH, Cheng YC, Liu YC, Cheng AJ, Lu YC, Chen YJ, Lin YW, Hsu CC, Chen YL, Lu CS, Wang HL. (2019.09) Upregulated expression of microRNA-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated apoptotic signaling cascade. Front Cell Neurosci 2019, 13:399. Doi: 10.3389/fncel.2019.00399. eCollection 2019.
  13. Li YC, Cheng AJ#, Lee LY, Huang YC, Chang JT*. (2019.07) Multifaceted mechanisms of areca nuts in oral carcinogenesis: the molecular pathology from precancerous condition to malignant transformation. J Cancer 2019, 10 (17): 4054-4062. Doi:10.7150/jca.29765. eCollection 2019.
  14. You GR, Cheng AJ#, Lee LY, Huang YC, Liu H, Chen YJ, Chang JT*. (2019.01) Prognostic signature associated with radioresistance in head and neck cancer via transcriptomic and bioinformatic analyses. BMC Cancer 2019, 19(1): 64. Doi: 10.1186/s12885-018-5243-3.
  15. Chen SH, Chao A, Tsai CL, Sue SC, Lin CY, Lee YZ, Hung YL, Chao AS, Cheng AJ, Wang HS, Wang TH. (2018.12) Utilization of HEPES for enhancing protein transfection into mammalian cells. Mol Ther Methods Clin Dev 2019, 13: 99-111. Doi: 10.1016/j.omtm.2018.12.005.
  16. Tsai CY, Chi HC, Chi LM, Yang HY, Tsai MM, Lee KF, Huang HW, Chou LF, Cheng AJ, Yang CW, Wang CS, Lin KH. (2018.05) Argininosuccinate synthetase 1 contributes to gastric cancer invasion and progression by modulating autophagy. FASEB J 2018, 32(5): 2601-2614. doi: 10.1096/fj.201700094R.
  17. Chen HY, Chang TC, Chien KY, Lee YS, You GR, Cheng AJ*. (2018.01) The endogenous Grp78 interactome in human head and neck cancers: a deterministic role of cell surface Grp78 in cancer stemness. Sci Rep 2018, 8(1): 536. Doi: 10.1038/s41598-017-14604-5. PMID: 29323121.
  18. Chen YJ, Kuo CC, Ting LL, Lu LS, Lu YC, Cheng AJ, Lin YT, Chen CH, Tsai JT, Chiou JF. (2018.02) Piperlongumine inhibits cancer stem cell properties and regulates multiple malignant phenotypes in oral cancer. Oncol Lett 2018, 15(2): 1789-1798. Doi: 10.3892/ol.2017.7486. PMID: 29399195.
  19. Lu YC, Cheng AJ#, Lee LY, You GR, Li YL, Chen HY, Chang JT*. (2017.05) MiR-520b as a novel molecular target for suppressing stemness phenotype of head-neck cancer by inhibiting CD44. Sci Rep 2017, 7 (1): 2042. Doi: 10.1038/s41598-017-02058-8.
  20. Li YL, Chang JT#, Lee LY, Fan KH, Lu YC, Li YC, Chiang CH, Chen HY, Cheng AJ*. (2017.01) GDF15 contributes to radioresistance and cancer stemness of head and neck cancer by regulating cellular reactive oxygen species via a SMAD-associated signaling pathway. Oncotarget 2017, 8 (1): 1508-1528. Doi: 10.18632/oncotarget.13649. PMID: 27903972
  21. Chiang CH, Wu CC, Lee LY, Li YC, Liu HP, Hsu CW, Lu YC, Chang JT, Cheng AJ*. (2016, 09) Proteomics analysis reveals involvement of Krt17 in areca nut – induced oral carcinogenesis. J Proteome Res 2016, 15: 2981-2997. Doi: 10.1021/acs.jproteome.6b00138. PMID: 27432155.
  22. Chao YK, Peng TL, Chuang WY, Yeh CJ, Li YL, Lu YC, Cheng AJ*. (2016.07) Transketolas serve a poor prognosticator in esophageal cancer by promoting cell invasion via epithelial – mesenchymal transition. J Cancer 2016, 7: 1408-1811. Doi: 10.7150/jca.15467. eCollection 2016.
  23. Lu YC, Chang JT, Chan EC, Chao YK, Yeh TS, Chen JS, Cheng AJ*. (2016.03) miR-196, an emerging cancer biomarker for digestive tract cancers. J Cancer 2016, 7(6): 650-655. Doi: 10.7150/jca.13460. PMID: 27076845.
  24. Li YC, Chang JT, Chiu C, Lu YC, Yi YL, Chiang CH, You GR, Lee LY, Cheng AJ*. (2016.05) Areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells. Mol Carcinog 2016, 55: 1012-1023. Doi: 10.1002/mc.22344. PMID: 26087469.
  25. Cheng CW, Hsiao JR, Fan CC, Lo YK, Tzen CY, Wu LW, Fang WY, Cheng AJ, Chen CH, Chang IS, Jiang SS, Chang JY, Lee AY. (2016.05) Loss of GDF10/BMP3b as a prognostic marker collaborates with TGFBR3 to enhance chemotherapy resistance and epithelial- mesenchymal transition in oral squamous cell carcinoma. Mol Carcinog 2016, 55(5): 499-513. Doi: 10.1002/mc.22297. PMID: 25728212.
  26. Martel J, Wu CY, Hung CY, Wong TY, Cheng AJ, Cheng ML, Shiao MS, Young JD. (2016.03) Fatty acids and small organic compounds bind to mineralo-organic nanoparticles derived from human body fluids as revealed by metabolomic analysis. Nanoscale 2016, 8(10): 5537-5545. Doi: 10.1039/c5nr08116e. PMID: 26818428
  27. Lee CH, Pank KL, Tang YC, Tsai MH, Cheng AJ, Shen MY, Cheng YM, Huang TT, Lin P. (2015.09) LDOC1 silenced by cigarette exposure and involved in oral neoplastic transformation. Oncotarget 2015, 6: 25188-25201. Doi: 10.18632/oncotarget.4512. PMID: 26317789.
  28. Lee LY, Chen YJ, Lu YC, Liao CT, Chen IH, Chang JTC, Huang YC, Chen WH, Huang CC, Tsai CY, Cheng AJ*. (2015.09) Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment. Clin Chem Lab Med 2015, 53: 1031-1641. Doi: 10.1515/cclm-2014-1016. PMID: 25781684.
  29. Lu YC, Chang JT, Huang YC, Huang CC, Chen WH, Lee LY, Huang BS, Chen YJ, Li HS, Cheng AJ*. (2015.02) Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer. Clin Biochem 2015, 48: 115-121. Doi: 10.1016/j.clinbiochem.2014.11.020. PMID: 25485932.
  30. Lu YC, Chang JT, Liao CT, Kang CJ, Huang SF, Chen IH, Huang CC, Huang YC, Chen WH, Tsai CY, Wang HM, Yen TC, You GR, Chiang CH, Cheng AJ*. (2014.09) OncomiR-196 promotes an invasive phenotype in oral cancer through the NEM4-JNK-TIMP1-MMP signaling pathway. Mol Cancer 2014, 13:218. Doi:10.1186/1476-4598-13-218. PMID: 25233933.
  31. Peng SC, Liao CT, Peng CH, Cheng AJ, Chen SJ, Huang CG, Hsieh WP, Yen TC. MicroRNA miR-218, mir-125b, and let-7g predict prognosis in patients with oral cavity squamous cell carcinoma. (2014.07) PLoS One 2014, 9: e102403. Doi: 10.1371/journal.pone.0102403. PMID: 25050624.
  32. Lu YC, Cheng AJ*. (2014.05). Pathological function and clinical significance of microRNA-10b in cancer. Cancer Sci Res Open Access 1(2): 1-5.
  33. Yen YC, Shiah SG, Chu HC, Hsu YM, Hsiao JR, Chang JY, Hung WC, Liao CT, Cheng AJ, Lu YC, Chen YW. (2014.01) Reciprocal regulation of microRNA-99a and insulin-like growth factor I receptor signaling in oral squamous cell carcinoma cells. Mol Cancer 2014, 13:6. Doi: 10.1186/1476-4598-13-6, PMID: 24410957.
  34. Huang WC, Chan SH, Jang TH, Chang JW, Ko YC, Yen TC, Chiang SL, Chiang WF, Shieh TY, Liao CT, Juang JL, Wang HC, Cheng AJ, Lu YC, Wang LH. (2014.02) miRNA-491-5p and GIT1 Serve as Modulators and Biomarkers for Oral Squamous Cell Carcinoma Invasion and Metastasis. Cancer Res 2014, 74:751-64. Doi: 10.1158/0008-5472.CAN-13-1297. PMID: 24335959.
  35. Chiu CC, Lee LY, Li YC, Chen YJ, Lu YC, Li YL, Wang HM, Chang JTC, Cheng AJ*. (2013.11) Grp78 as a therapeutic target for refractory head-neck cancer with CD24-CD44+ stemness phenotype. Cancer Gene Ther 2013, 20: 606-615. Doi: 10.1038/cgt.2013.64. PMID: 24201869.
  36. Chen YJ, Lee LY, Chao YK, Chang JT, Lu YC, Li HF, Chiu CC, Li YL, Chiou JF, Cheng AJ*. (2013.05) DSG3 facilitates cancer cell growth and invasion through the DSG3- plakoglobin - TCF/LEF - myc/cyclinD1/ MMP signaling pathway. PLoS One 2013, 8: e60488. Doi: 10.1371/journal.pone.0064088. PMID: 23737966.
  37. Lee CH, Wong TS, Chan JY, Lu SC, Lin P, Cheng AJ, Chen YJ, Chang JS, Hsiao SH, Leu YW, Li CI, Hsiao JR, Chang JY. (2013.07) Epigenetic regulation of the X-linked tumor suppressors BEX1 and LDOC1 in oral squamous cell carcinoma. J Pathol 2013, 230: 298-309. Doi: 10.1002/path.4173.
  38. Wu YM, Su F, Kalyana-Sundaram S, Khazanov N, Ateeq B, Cao X, Lonigro RJ, Vats P, Wang R, Lin SF, Cheng AJ, et al. (2013.06) Identification of targetable EGFR gene fusions in diverse cancers. Cancer Discov 2013, 3:636-647. Doi: 10.1158/2159-8290.CD-13-0050. PMID: 23558953.
  39. Jian SL, Hsieh HY, Liao CT, Yen TC, Nien SW, Cheng AJ, Juang JL. (2013.06) Ga12 drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. PLoS One 2013, 8: e66133. Doi: 10.1371/journal.pone.0066133. PMID: 23762476.
  40. Le QT, Zhang Q, Cao H, Cheng AJ, Pinsky BA, Hong RL, Chang JT, Wang CW, Tsao KC, Lo YD, Lee NY, Ang KK, Chan AT, Chan KA. (2013.04) An international collaboration to harmonize the quantitative plasma Epstein-Barr Virus (EBV) DNA assay for future biomarker-guided rrials in nasopharyngeal carcinoma. Clin Cancer Res 2013, 19: 2208-2015.Doi: 10.1158/1078-0432. CCR-12-3702. PMID: 23459720.
  41. Huang SF, Li HF, Liao CT, Wang HM, Chen IH, Chang JTC, Chen YJ, Cheng AJ*. (2012. 11) Association of HPV infection with second primary tumors in early staged oral cavity cancer. Oral Disease 2012, 18: 809-815. Doi: 10.1111/j.1601-0825.2012.01950.x. PMID: 22747969.
  42. Tsai JP, Lee MH, Hsu SC, Chen MY, Liu SJ, Chang JT, Liao CT, Cheng AJ, Chong P, Chu CL, Shen CR, Chen HW. (2012.08) CD4+ T cells disarm or delete cytotoxic T lymphocytes under IL-17 polarizing conditions.  J Immunol 2012, 189: 1671-1679. Doi: 10.4049/jimmunol.1103447. PMID: 22798680.
  43. Lu YC, Chen YJ, Wang HM, Tsai CY, Chen WH, Huang YC, Fan KH, Tsai CN, Huang SF, Kang CJ, Chang JT, Cheng AJ*. (2012.04) Oncogenic function and early detection potential of miRNA-10b in oral cancer as identified by microRNA profiling. Cancer Prev Res 2012, 5:665-674.Doi: 10.1158/1940-6207.CAPR-11-0358. PMID: 22318752.
  44. Chao YK, Chuang WY, Yeh CJ, Wu YC, Liu YH, Hsieh MJ, Cheng AJ, Hsueh C, Liu HP (2012, 02). Prognostic significance of high podoplanin expression after chemoradiotherapy in esophageal squamous cell carcinoma patients. J Surg Oncol 2012, 105:183-188. Doi: 10.1002/jso.22068. PMID: 22213642.
  45. Lin CY, Lin TY, Wang HM, Huang SF, Fan KH, Liao CT, Chen IH, Lee LY, Li YL, Chen YJ, Cheng AJ*, Chang JT. (2011.11) GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy. Radiat Oncol 2011, 6: 136-143.Doi: 10.1186/1748-717X-6-136. PMID: 21992474.
  46. Peng CH, Liao CT, Peng SC, Chen YJ, Cheng AJ, Juang JL, Tsai CY, Chen TC, Chuang YJ, Tang CY, Hsieh WP, Yen TC. (2011.06) A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma. PLoS One. 2011, 6: e23452.Doi: 10.1371/journal.pone.0023452. PMID: 21853135.
  47. Chiu CC, Lin CY, Lee LY, Chen YJ, Lu YC, Wang HM, Liao CT, Chang JT, Cheng AJ*. (2011, 07) Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. Clin Cancer Res 2011, 17: 4629-4641. doi: 10.1158/1078-0432.CCR-10-2107. PMID: 21642380.
  48. Chen YJ, Liao CT, Chen PJ, Lee LY, Li YC, Chen IH, Wang HM, Chang JTC, Chen LJ, Yen TC, Tang CY, Cheng AJ*. (2011, 3) Down-regulation of Ches1 and other novel genes in oral cancer cells chronically exposed to areca nut extract. Head Neck 2011, 33: 257-266. Doi: 10.1002/hed.21442.. PMID: 20848451.
  49. Chang JTC, Kuo TF, Chen YJ, Chiu CC, Lu YC, Li HS, Wang HM, Shen CR, Cheng AJ*. (2010, 12) Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers. Cancer Gene Ther 2010, 17: 827-836. Doi: 10.1038/cgt.2010.38. PMID: 20885450.
  50. Lin TY, Chang JTC, Wang HM, Chan SH, Chiu CC, Lin CY, Fan KH, Liao CT, Chen IH, Liu TZ, Li HF, Cheng AJ*. (2010.09) Proteomics of the radioresistant phenotype in head-and-neck cancer: GP96 as a novel prediction marker and sensitizing target for radiotherapy. Int J Radiat Oncol Biol Phys 2010, 78: 246-256. Doi: 10.1016/j.ijrobp.2010.03.002. PMID: 20615631.
  51. Lin CY, Chen WH, Liao CT, Chen IH, Chiu CC, Wang HM, Yen TC, Lee LY, Chang JT, Cheng AJ*. (2010, 8) Positive association of Grp78 during oral cancer progression and the prognostic value in oral precancer lesions. Head Neck 2010, 32: 1028-1039. Doi: 10.1002/hed.21287. PMID: 19953611.
  52. Liao CT, Wang HM, Chang JT, Lin CY, Ng SH, Huang SF, Chen IH, Hsueh C, Lee LY, Lin CH, Cheng AJ, Yen TC. (2010.06) Influence of pathological nodal status and maximal standardized uptake value of the primary tumor and regional lymph nodes on treatment plans in patients with advanced oral cavity squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2010; 77: 421-429.Doi: 10.1016/j.ijrobp.2009.05.002. PMID: 20457351.
  53. Wu YH, Wang HM, Chen HW, Lin CY, Chen YE, Fan KH, Huang SF, Chen IH, Liao CT, Cheng AJ, Chang JT. (2010, 3) Hypothyroidism after radiotherapy for nasopharyngeal cancer patients. Int J Radiat Oncol Biol Phys 2010, 76: 1133-1139. Doi: 10.1016/j.ijrobp.2009.03.011. PMID: 19596170.