1. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
2. School of Medicine, I-Shou University, Kaohsiung, Taiwan
3. Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan
4. Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
5. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan
6. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
7. Department of Medical Research, Chi-Mei Medical Center, Chiali Branch, Tainan, Taiwan
#These two authors equally contributed to this work.
Background: Due to the varying characteristics and conflicting outcomes on the overall survival of rectal cancer patients, many studies have been undertaken to determine various prognostic and predictive factors for the mainstay treatment of CCRT followed by surgery. Cancer cell motility contributes to tumor invasion, migration and eventually metastasis. However, the genes associated with cell motility (i.e., GO:0048870) have not been systemically evaluated in rectal cancers.
Methods: A comparative analysis of gene expression profiles was applied to the transcriptomic dataset (GSE35452) with a focus on genes associated with cell motility (GO:0048870), where SERPINB5 was recognized as the most significantly up-regulated gene. Tumor samples from 172 primary rectal cancer patients who underwent neoadjuvant CCRT followed by surgical resection were collected. Immunohistochemistry was used to semi-quantitatively assess the expression level of SERPINB5 protein. Statistical analyses of SERPINB5 expression and various clinicopathological features as well as survival were then performed.
Results: High immunoreactivity of SERPINB5 was significantly linked to pre- and post-CCRT advanced disease, lymphovascular invasion, and poor response to CCRT (all P ≤ 0.015). SERPINB5 overexpression was not only negatively associated with disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) rates in univariate analyses but also was an independent prognostic factor for DSS and MeFS in rectal cancer patients (all P ≤ 0.043).
Conclusion: SERPINB5 may play an important role in rectal cancer progression and response to neoadjuvant CCRT and serve as a novel prognostic factor.
Keywords: CCRT, chemoradiotherapy, Maspin, rectal cancer, SERPINB5