Down-Regulation of an Autophagy-Related Gene SERPINA1 as a Superior Prognosis Biomarker Associates with Relapse and Distant Metastasis in Colon Adenocarcinoma

Chen Fu,1,2 Zhaojin Yu,1,2 Ying He,1,3 Jian Ding,1,4 Minjie Wei1,2,5 1Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People’s Republic of China; 2Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Department of Pharmacology, China Medical University, Shenyang, 110122, People’s Republic of China; 3Department of Oncology, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110000, People’s Republic of China; 4Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China; 5Liaoning Medical Diagnosis and Treatment Center, Shenyang, 110000, People’s Republic of ChinaCorrespondence: Jian DingDivision of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of ChinaEmail carl.2000@163.comMinjie WeiDepartment of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People’s Republic of ChinaEmail weiminjiecmu@163.comBackground: The relapse and distant metastasis in colon adenocarcinoma (COAD) patients with a poor prognosis. Autophagy has gained increasing attention recently.Methods: This study utilized univariate Cox analysis from the TCGA database to obtain 10 prognostic autophagy-related genes (ARGs). GO and KEGG functional annotation analysis suggested that the ARGs were significantly enriched in tumor metabolic processes. We verified the autophagy-related genes screened by TCGA clinical data. Then, we compared the expression of SERPINA1 in primary and metastatic tumor cells in the GEO database, and finally verified the relationship between SERPINA1 protein expression and prognosis with the CPTAC database.Results: The ROC curves showed SERPINA1 had robust prediction capability in judging the prognosis and disease process compared with the other 4 ARGs and risk score in COAD. Clinical relationship analysis further indicated SERPINA1 was related to TMN stage, clinical-stage, OS, RFS, and DMFS in COAD. Besides, survival analysis presented that higher expression of SERPINA1 was significantly associated with the longer OS, RFS, or DMFS. Moreover, SERPINA1 protein was validated to be associated with OS, RFS, and DMFS through our own IHC and CPTAC database. Finally, we exploratoryly combined the SERPINA1 mRNA and SERPINA1 protein as a new index for prognostics.Conclusion: This new combined index showed the highest prognostic value for OS, RFS, and DMFS, and had the potential to become a practical biomarker for prognosis.Keywords: SERPINA1, autophagy, COAD, prognostic, relapse, distant metastasis