Oncotarget

Research Papers:

Lysosomal acid phosphatase 2 is an unfavorable prognostic factor but is associated with better survival in stage II colorectal cancer patients receiving chemotherapy

Yu-Chieh Lee, Chia-Yu Su, Yuan-Feng Lin, Chun-Mao Lin, Chih-Yeu Fang, Yen-Kuang Lin, Michael Hsiao and Chi-Long Chen _

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Oncotarget. 2017; 8:12120-12132. https://doi.org/10.18632/oncotarget.14552

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Abstract

Yu-Chieh Lee1,9, Chia-Yu Su2, Yuan-Feng Lin3, Chun-Mao Lin4, Chih-Yeu Fang7, Yen-Kuang Lin8, Michael Hsiao2,10, Chi-Long Chen5,6

1Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

2Genomics Research Center, Academia Sinica, Taipei, Taiwan

3Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan

4Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei, Taiwan

5Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan

6Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan

7Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

8Biostatistics Center, Taipei Medical University, Taipei, Taiwan

9Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

10Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Correspondence to:

Chi-Long Chen, email: [email protected]

Michael Hsiao, email: [email protected]

Keywords: colorectal carcinoma, lysosomal acid phosphatase 2, 5-FU, chemotherapy

Received: July 05, 2016     Accepted: December 27, 2016     Published: January 06, 2017

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.

Highlights

1. 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.


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