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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.