Small heterodimer partner as a predictor of neoadjuvant radiochemotherapy response and survival in patients with rectal cancer: A preliminary study

Kim,Sup; Joo,Mina; Yeo,Min-Kyung; Cho,Moon-June; Kim,Jun-Sang; Jo,Eun-Kyeong; Kim,Jin-Man

doi:10.3892/ol.2021.12969

Small heterodimer partner as a predictor of neoadjuvant radiochemotherapy response and survival in patients with rectal cancer: A preliminary study

Authors:
- Sup Kim
- Mina Joo
- Min-Kyung Yeo
- Moon-June Cho
- Jun-Sang Kim
- Eun-Kyeong Jo
- Jin-Man Kim
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Affiliations: Department of Radiation Oncology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea, Department of Pathology and Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea, Department of Microbiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
Published online on: August 4, 2021 https://doi.org/10.3892/ol.2021.12969
Article Number: 708
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Small heterodimer partner (SHP) plays an essential role in the regulation of innate immune and inflammatory responses. The aim of the present study was to identify whether SHP levels are associated with cancer immunology and treatment outcomes in rectal cancer. SHP expression was analyzed via gene set enrichment analysis and the OncoLnc database. In addition, immunohistochemistry and reverse transcription‑quantitative PCR analyses were performed on the tissues of patients with locally advanced rectal cancer, and the associations of SHP expression with the clinicopathological and hematological features or treatment response to preoperative radiochemotherapy (pRCT) were analyzed retrospectively. Furthermore, the present study investigated whether SHP expression correlated with immune infiltration levels and immune checkpoint molecules in rectal cancer. The results revealed that low SHP mRNA expression was significantly associated with an inflammatory response and poor prognosis. The nuclear expression of SHP was associated with clinical N stage, neutrophil count, lymphocyte count, neutrophil‑lymphocyte ratio and complete pathologic response following pRCT. The low nuclear expression of SHP was associated with poor overall and distant metastasis‑free survival (DMFS). In multivariate analysis, the low nuclear expression of SHP was identified as a significant independent prognostic factor for DMFS and a marginally significant prognostic factor for overall survival in rectal cancer. Furthermore, patients with low SHP expression exhibited higher neutrophil and CD8⁺ T cell infiltration levels and higher PD‑L1 expression in rectal adenocarcinoma. These results indicate that SHP may act as an anti‑inflammatory mediator via the regulation of systemic and local immune responses in rectal cancer. Moreover, SHP might be useful a potential marker or therapeutic target in rectal cancer.

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