Kim Baek-Hui, Jung Woon Yong, Lee Hyunjoo, Kang Youngran, Jang You-Jin, Hong Soon Won, Jeong Hyeong-Jae, Yoon Sun Och
Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
Ann Surg Oncol. 2014 Jun;21(6):2020-7. doi: 10.1245/s10434-014-3522-z. Epub 2014 Feb 21.
Lysyl-tRNA synthetase (KRS) is an aminoacyl-tRNA synthetase (ARS) that is essential for protein synthesis during ligation of specific amino acids to their cognate tRNAs. Aberrant expression of ARSs is associated with various human cancers.
Using immunohistochemical detection, the present study analyzed the clinical relevance of KRS expression in tumor cells and tumor-associated inflammatory cells (TAI) in 457 patients who underwent curative radical surgery and standard adjuvant therapy and who were observed on long-term follow-up.
High expression of KRS in tumor cells (tumor-KRS(+)) was noted in 43.3 % (198 of 457) of cases. High expression of KRS in tumor-associated inflammatory cells (TAI-KRS(+)) including macrophages/monocytes, CD4-positive T cells, and/or neutrophils was observed in 37.2 % (170 of 457) of cases. Status of KRS in the tumor and TAI revealed an association with the known clinicopathological parameters for prognosis of gastric cancer. Tumor-KRS(+) status correlated to shorter overall survival, especially in stage III to IV cancers (P = 0.003), while TAI-KRS(+) status correlated significantly to longer overall survival in gastric cancer (P = 0.049). Cases with tumor-KRS(+) and TAI-KRS(-) status showed significantly reduced survival rates compared to those of other cases (P = 0.010), and status of tumor-KRS(+) and TAI-KRS(-) was revealed as an independently poor prognostic factor of overall survival (P = 0.001).
KRS-related inflammation can be identified in a subset of gastric cancer. This may be a possible mechanism of immune surveillance against tumor progression. In addition, expression status of KRS in tumor and TAI may be an independent prognostic marker for gastric cancer patients.
赖氨酰 - tRNA合成酶(KRS)是一种氨酰 - tRNA合成酶(ARS),在特定氨基酸与其同源tRNA连接过程中对蛋白质合成至关重要。ARS的异常表达与多种人类癌症相关。
本研究采用免疫组化检测方法,分析了457例行根治性手术及标准辅助治疗且接受长期随访的患者肿瘤细胞及肿瘤相关炎性细胞(TAI)中KRS表达的临床相关性。
43.3%(457例中的198例)的病例肿瘤细胞中KRS呈高表达(肿瘤 - KRS(+))。37.2%(457例中的170例)的病例肿瘤相关炎性细胞(包括巨噬细胞/单核细胞、CD4阳性T细胞和/或中性粒细胞)中KRS呈高表达(TAI - KRS(+))。肿瘤及TAI中KRS状态与已知的胃癌预后临床病理参数相关。肿瘤 - KRS(+)状态与总生存期缩短相关,尤其是在III至IV期癌症中(P = 0.003),而TAI - KRS(+)状态与胃癌患者总生存期显著延长相关(P = 0.049)。与其他病例相比,肿瘤 - KRS(+)且TAI - KRS(-)状态的病例生存率显著降低(P = 0.010),肿瘤 - KRS(+)且TAI - KRS(-)状态被揭示为总生存期独立的不良预后因素(P = 0.001)。
在一部分胃癌中可发现KRS相关炎症。这可能是针对肿瘤进展的免疫监视的一种可能机制。此外,肿瘤及TAI中KRS的表达状态可能是胃癌患者的独立预后标志物。