Kirana Chandra, Ruszkiewicz Andrew, Stubbs Richard S, Hardingham Jennifer E, Hewett Peter J, Maddern Guy J, Hauben Ehud
Liver Metastasis Research Group, Department of Surgery, The Basil Hetzel Institute, University of Adelaide, South Australia.
Division of Surgical Pathology, The Royal Adelaide Hospital, North Terrace Adelaide, South Australia.
Int J Cancer. 2017 Jun 1;140(11):2577-2586. doi: 10.1002/ijc.30667. Epub 2017 Mar 24.
The expression of HLA-G by tumour cells is an established mechanism to escape recognition and immune mediated destruction, allowing tumour survival, growth and metastasis. However, the prognostic value of soluble HLA-G (sHLA-G) remains unknown. Mucinous carcinoma (MC) is a distinct form of colorectal cancer (CRC) found in 10 to 15% of patients, which has long been associated with poor response to treatment. To investigate the prognostic value of plasma sHLA-G levels in CRC patients, preoperative plasma sHLA-G levels were determined by ELISA in CRC patients (n = 133). In addition, the local expression of HLA-G in tumour biopsies was assessed using tissue microarray analysis (n = 255). Within the high 33rd percentile of sHLA-G levels (265-890 U/mL; n = 44) we observed higher frequency of MC patients (p = 0.012; Chi-square), and higher sHLA-G levels in patients with vascular invasion (p = 0.035; two-tailed t-test). Moreover, MC patients had significantly higher sHLA-G levels compared to those with adenocarcinoma not otherwise specified (p = 0.036; two-tailed t-test). Surprisingly, while stage II patients showed negative correlation between sHLA-G levels and liver metastasis free survival (LMFS) (p = 0.041; R = -0.321), in stage III patients high sHLA-G levels were associated with significantly longer LMFS (p = 0.002), and sHLA-G levels displayed positive correlation with LMFS (p = 0.006; R = 0.409). High HLA-G expression in tumours was associated with poor cancer specific overall survival in stage II to III (p = 0.01), and with shorter LMFS in stage II patients (p = 0.004). Our findings reveal that sHLA-G levels are associated with distinct progression patterns in consecutive disease stages, indicating a potential value as surrogate marker in the differential prognosis of CRC.
肿瘤细胞表达HLA - G是一种逃避识别和免疫介导破坏的既定机制，可使肿瘤存活、生长和转移。然而，可溶性HLA - G（sHLA - G）的预后价值仍不明确。黏液腺癌（MC）是结直肠癌（CRC）的一种特殊形式，见于10%至15%的患者，长期以来一直与治疗反应不佳相关。为了研究血浆sHLA - G水平在CRC患者中的预后价值，通过酶联免疫吸附测定（ELISA）法测定了133例CRC患者术前血浆sHLA - G水平。此外，使用组织微阵列分析评估了肿瘤活检组织中HLA - G的局部表达（n = 255）。在sHLA - G水平处于第33百分位数以上（265 - 890 U/mL；n = 44）的患者中，我们观察到MC患者的频率更高（p = 0.012；卡方检验），且血管侵犯患者的sHLA - G水平更高（p = 0.035；双侧t检验）。此外，与未另作说明的腺癌患者相比，MC患者的sHLA - G水平显著更高（p = 0.036；双侧t检验）。令人惊讶的是，虽然II期患者的sHLA - G水平与无肝转移生存期（LMFS）呈负相关（p = 0.041；R = - 0.321），但在III期患者中，高sHLA - G水平与显著更长的LMFS相关（p = 0.002），且sHLA - G水平与LMFS呈正相关（p = 0.006；R = 0.409）。肿瘤中高HLA - G表达与II至III期患者较差的癌症特异性总生存期相关（p = 0.01），且与II期患者较短的LMFS相关（p = 0.004）。我们的研究结果表明，sHLA - G水平与连续疾病阶段中不同的进展模式相关，表明其在CRC的鉴别预后中作为替代标志物具有潜在价值。
