KLK10/LIPH/PARD6B/SLC52A3 are promising molecular biomarkers for the prognosis of pancreatic cancer through a ceRNA network
Meng Zhang,
Lin Jiang,
Xin-Yun Liu,
Fu-Xing Liu,
Hui Zhang,
Yan-Juan Zhang,
Xiao-Mei Tang,
Yu-Shui Ma,
Hui-Yi Wu,
Xun Diao,
Chun Yang,
Ji-Bin Liu,
Da Fu,
Jie Zhang,
Hong Yu
Affiliations
Meng Zhang
Department of Immunology, School of Medicine, Nantong University, Nantong, 226019, Jiangsu, China; Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China; Institute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, Jiangsu, China
Lin Jiang
Department of Anesthesiology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China
Xin-Yun Liu
Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
Fu-Xing Liu
Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
Hui Zhang
Institute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, Jiangsu, China
Yan-Juan Zhang
Department of Immunology, School of Medicine, Nantong University, Nantong, 226019, Jiangsu, China; Department of Clinical Laboratory, Affiliated Maternity & Child Health Care Hospital of Nantong University, Nantong, 226019, Jiangsu, China
Xiao-Mei Tang
General Surgery, Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, Shanghai, China
Yu-Shui Ma
Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, Shanghai, China
Hui-Yi Wu
Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China
Xun Diao
Institute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, Jiangsu, China
Chun Yang
Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
Ji-Bin Liu
Institute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, Jiangsu, China; Corresponding author.
Da Fu
Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China; Institute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226631, Jiangsu, China; General Surgery, Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, Shanghai, China; Corresponding authors. Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China.
Jie Zhang
Department of Immunology, School of Medicine, Nantong University, Nantong, 226019, Jiangsu, China; Corresponding authors.
Hong Yu
Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, Jiangsu, China; Department of Pathology, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, Jiangsu, China; Corresponding author. Department of Pathology, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, Jiangsu, China.
Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%–90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.
