title: Lysosomal acid phosphatase 2 is an unfavorable prognostic factor but is associated with better survival in stage II colorectal cancer patients receiving chemotherapy.
abstract: Colorectal cancer (CRC) is one of the leading cancers worldwide. Surgery is the main therapeutic modality for stage II CRC. However, the implementation of adjuvant chemotherapy remains controversial and is not universally applied so far. In this study, we found that the protein expression of lysosomal acid phosphatase 2 (ACP2) was increased in CRC and that stage II CRC patients with high ACP2 expression showed a poorer outcome than those with low ACP2 expression (p = 0.004). To investigate this discrepancy, we analyzed the relation between ACP2 expression and several clinical cofactors.Among patients who received chemotherapy, those with an high expression of ACP2 showed better survival in both stage II and III CRC than those with low ACP2 expression. In stage II CRC patients, univariate analysis showed ACP2 expression and T stage to be cofactors significantly associated with overall survival (ACP2: p = 0.006; T stage: p = 0.034). Multivariate Cox proportion hazard model analysis also revealed ACP2 to be an independent prognostic factor for overall survival (ACP2: p = 0.006; T stage: p = 0.041). Furthermore, ACP2-knockdown CRC cells showed an increase in chemoresistance to 5-FU treatment and increased proliferation marker in the ACP2 knockdown clone.Taken together, our results suggested that ACP2 is an unfavorable prognostic factor for stage II CRC and may serve as a potential chemotherapy-sensitive marker to help identify a subset of stage II and III CRC patients for whom chemotherapy would improve survival.Highlights1. To the best of our knowledge, the study is the first report to show ACP2 overexpression in human colorectal cancer (CRC) and its association with poor outcome in stage II CRC.2. Patients with stage II and III CRCs with high expression of ACP2 were more sensitive to chemotherapy than those with a low expression.3. ACP2 expression may serve as a marker for CRC patients receiving chemotherapy and help identify the subset of CRC patients who would benefit from chemotherapy.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Su
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Mao
authors.initials: CM
authors.lastname: Lin
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.affiliation: Biostatistics Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yen-Kuang
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C520783:ACP2 protein, human; D000135:Acid Phosphatase; D005472:Fluorouracil
keywords: 5-FU; chemotherapy; colorectal carcinoma; lysosomal acid phosphatase 2