Clinicopathological profiling of small heterodimer partner, as a negative regulator of inflammatory responses in rectal cancer patients

Abstract Background: Small heterodimer partner (SHP) is an orphan nuclear receptor family member that plays an essential role in the regulation of innate immune and inflammatory responses. However, the expression of SHP in rectal cancer and its prognostic significance have not been investigated. The aim of this study was to identify whether SHP levels are associated with cancer-related inflammation, treatment response and prognosis in rectal cancer patients. Methods: First, we performed classic gene set enrichment analysis (GSEA) to detect the association between high and low SHP expression using TCGA data sets. Then, the correlation between the expression of SHP and the prognosis of rectal cancer patients was evaluated using online OncoLnc database. Finally, we performed immunohistochemistry and analysed the correlation between SHP expression and clinicopathological / haematolgic features or treatment response of rectal cancer patients treated with radiochemotherapy. Results: Bioinformatics analysis indicated that low SHP mRNA expression was significantly associated with inflammatory response (NES = -1.67507) and poor prognosis (p = 0.0319). Nuclear expression of SHP was associated with cN stage (p = 0.003), Neutrophil (p = 0.023), Lymphocyte (p = 0.024), NLR (p = 0.023) and complete pathologic response after radiochemotherapy (p = 0.031). Low nuclear expression of SHP was associated with poor overall and distant metastasis-free survival for rectal cancer (p = 0.029 and p = 0.008) and retained significance as an independent prognostic factor for rectal cancer (p = 0.087 and p = 0.037). Conclusions: These results inidcate that SHP may act as an antiinflammatory mediator by regulating systemic and local immune responses in rectal cancer. Moreover, SHP might be used a candidate markers or therapeutic target in rectal cancer.