PMID- 31455288 OWN - NLM STAT- MEDLINE DCOM- 20200124 LR - 20200225 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 19 IP - 1 DP - 2019 Aug 27 TI - PLOD2 contributes to drug resistance in laryngeal cancer by promoting cancer stem cell-like characteristics. PG - 840 LID - 10.1186/s12885-019-6029-y [doi] LID - 840 AB - BACKGROUND: Advanced stage laryngeal squamous cell carcinoma (LSCC) presents a poor prognosis; thus, there is a great need to identify novel prognostic molecular markers. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is thought to be a novel prognostic factor in several cancers, but its role in LSCC remains unknown. Cancer stem cells (CSCs) are responsible for most instances of tumor recurrence and the development of drug resistance and have been proven to be present in head and neck cancers. Our preliminary study indicated that PLOD2 was elevated in LSCC tissues; therefore, we hypothesized that PLOD2 is related to the prognosis of LSCC patients and aimed to explore the role and underlying mechanism of PLOD2 in LSCC. METHODS: We validated the prognostic role of PLOD2 in 114 LSCC patients by immunohistochemistry. Stable PLOD2-overexpressing Hep-2 and FaDu cells were established and assessed by molecular biology and biochemistry methods both in vitro and in vivo. RESULTS: We confirmed that PLOD2 overexpression was correlated with poor prognosis in LSCC patients. PLOD2 overexpression strengthened the CSC-like properties of Hep-2 and FaDu cells, activated the Wnt signaling pathway and conferred drug resistance in LSCC in vitro and in vivo. CONCLUSIONS: We found that PLOD2 could serve as a prognostic marker in patients with LSCC and confer drug resistance in LSCC by increasing CSC-like traits; in addition, a Wnt-responsive CSC pathway was identified. FAU - Sheng, Xiaoli AU - Sheng X AD - Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China. AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, No.106, Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China. FAU - Li, Yunxian AU - Li Y AD - Shantou University Medical College, Shantou, Guangdong, China. FAU - Li, Yixuan AU - Li Y AD - Head and Neck Surgery of Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Liu, Wenlin AU - Liu W AD - Department of Otorhinolaryngology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China. FAU - Lu, Zhongming AU - Lu Z AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, No.106, Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China. FAU - Zhan, Jiandong AU - Zhan J AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, No.106, Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China. FAU - Xu, Mimi AU - Xu M AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, No.106, Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China. FAU - Chen, Liangsi AU - Chen L AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, No.106, Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China. FAU - Luo, Xiaoning AU - Luo X AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, No.106, Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China. FAU - Cai, Gang AU - Cai G AD - The Fifth Affiliated Hospital of Guangzhou Medical University, No.621, Gangwan Road, Guangzhou, 510700, Guangdong Province, China. aacggin@163.com. FAU - Zhang, Siyi AU - Zhang S AD - Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China. shengzhang2016@126.com. AD - Department of Otorhinolaryngology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, No.106, Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China. shengzhang2016@126.com. LA - eng GR - 201607010389/Guangzhou Science, Technology and Innovation Commission/ PT - Journal Article DEP - 20190827 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - EC 1.14.11.4 (PLOD2 protein, human) RN - EC 1.14.11.4 (Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Antineoplastic Agents/pharmacology MH - Biomarkers, Tumor MH - Cell Line, Tumor MH - Disease Models, Animal MH - Drug Resistance, Neoplasm/*genetics MH - Female MH - Humans MH - Immunohistochemistry MH - Laryngeal Neoplasms/*genetics/metabolism/mortality/pathology MH - Male MH - Mice MH - Middle Aged MH - Neoplasm Grading MH - Neoplasm Staging MH - Neoplastic Stem Cells/*drug effects/*metabolism MH - Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/*genetics/metabolism MH - Prognosis MH - Wnt Signaling Pathway MH - Xenograft Model Antitumor Assays PMC - PMC6712771 OTO - NOTNLM OT - Cancer stem cells OT - Drug resistance OT - Laryngeal squamous cell carcinoma OT - PLOD2 OT - Wnt/beta-catenin pathway COIS- The authors declare that they have no competing interests. EDAT- 2019/08/29 06:00 MHDA- 2020/01/25 06:00 PMCR- 2019/08/27 CRDT- 2019/08/29 06:00 PHST- 2019/01/15 00:00 [received] PHST- 2019/08/08 00:00 [accepted] PHST- 2019/08/29 06:00 [entrez] PHST- 2019/08/29 06:00 [pubmed] PHST- 2020/01/25 06:00 [medline] PHST- 2019/08/27 00:00 [pmc-release] AID - 10.1186/s12885-019-6029-y [pii] AID - 6029 [pii] AID - 10.1186/s12885-019-6029-y [doi] PST - epublish SO - BMC Cancer. 2019 Aug 27;19(1):840. doi: 10.1186/s12885-019-6029-y.