Kim Sup, Joo Mina, Yeo Min-Kyung, Cho Moon-June, Kim Jun-Sang, Jo Eun-Kyeong, Kim Jin-Man
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.
Oncol Lett. 2021 Oct;22(4):708. doi: 10.3892/ol.2021.12969. Epub 2021 Aug 4.
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.
小异源二聚体伴侣蛋白（SHP）在先天性免疫和炎症反应的调节中发挥着重要作用。本研究的目的是确定SHP水平是否与直肠癌的癌症免疫学及治疗结果相关。通过基因集富集分析和OncoLnc数据库分析SHP表达。此外，对局部晚期直肠癌患者的组织进行免疫组织化学和逆转录定量PCR分析，并回顾性分析SHP表达与临床病理和血液学特征或术前放化疗（pRCT）治疗反应的相关性。此外，本研究还探讨了SHP表达是否与直肠癌中的免疫浸润水平和免疫检查点分子相关。结果显示，SHP mRNA低表达与炎症反应及不良预后显著相关。SHP的核表达与临床N分期、中性粒细胞计数、淋巴细胞计数、中性粒细胞与淋巴细胞比值以及pRCT后的完全病理反应相关。SHP核低表达与总生存期和无远处转移生存期（DMFS）较差相关。在多变量分析中，SHP核低表达被确定为直肠癌DMFS的显著独立预后因素和总生存期的边缘显著预后因素。此外，SHP表达低的患者在直肠腺癌中表现出更高的中性粒细胞和CD8 T细胞浸润水平以及更高的PD-L1表达。这些结果表明，SHP可能通过调节直肠癌的全身和局部免疫反应而作为一种抗炎介质。此外，SHP可能是直肠癌中一种潜在的标志物或治疗靶点。
