PCSK1 Overexpression in Rectal Cancer Correlates with Poor Response to Preoperative Chemoradiotherapy and Prognosis

BACKGROUND: In a data mining search for potential therapeutic targets to improve the outcome of rectal cancer, we identified PCSK1 as the cell–cell signaling gene most significantly associated with poor response to concurrent chemoradiotherapy (CCRT). This study aims to investigate the prognostic value of PCSK1 expression in rectal cancer patients who underwent neoadjuvant CCRT. METHODS: Endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery were assessed immunohistochemically for PCSK1 expression, and H-scores were determined. Expression levels of PCSK1 were further analyzed for correlations with clinicopathologic features, tumor regression grade, metastasis-free survival, disease-specific survival, and recurrence-free survival. RESULTS: PCKS1 overexpression was significantly associated with pretreatment tumor status (T3–4; p = 0.009), pretreatment nodal status (N1–2; p < 0.001), posttreatment tumor status (T3–4; p < 0.001), posttreatment nodal status (N1–2; p < 0.001), vascular invasion (p = 0.003), and perineurial invasion (p = 0.023). PCKS1 overexpression was also found to be significantly associated with a lower degree of tumor regression (p < 0.001). In the univariate analysis, PCSK1 overexpression was significantly associated with lower disease-specific survival, metastasis-free survival, and recurrence-free survival (p < 0.005). PCSK1 overexpression remained an independent prognostic factor of lower disease-specific survival (p = 0.003; hazard ratio, 5.478) in the multivariate analysis. CONCLUSION: Determination of PCSK1 overexpression may be useful for identifying rectal cancer patients at risk for a poor response and worse survival after CCRT.