Department of Pathology, Jeju National University School of Medicine and Jeju National University Hospital, Jeju, Republic of Korea.
Department of Internal Medicine, Jeju National University School of Medicine and Jeju National University Hospital, Jeju, Republic of Korea.
Anticancer Res. 2021 Jul;41(7):3689-3698. doi: 10.21873/anticanres.15160.
BACKGROUND/AIM: SPARC-related modular calcium-binding protein 2 (SMOC2), a secreted matricellular protein, is reported to be involved in cancer progression such as cell cycle, angiogenesis, and invasion. In this study, we aimed to investigate the expression of SMOC2 in various gastric lesions and assessed its prognostic value in a large cohort of gastric cancer (GC) patients.
SMOC2 mRNA levels were measured by quantitative real-time PCR using 26 matched fresh-frozen GC samples. SMOC2 protein expression was determined by immunohistochemistry on tissue microarrays including 734 GC specimens and its correlations with clinicopathological features and survival were evaluated.
The transcription level of SMOC2 was higher in GC samples compared to normal mucosa (p=0.006). Its expression levels were associated with the intestinal stem cell (ISC) marker, LGR5, but there were no correlations with EPHB2 and OLFM4 or the candidate cancer stem cell markers CD133 and CD44. SMOC2 expression was significantly increased in the intestinal metaplasia and was further increased in gastric adenomas and early gastric cancers (EGC). In total, 34% of GCs were positive for SMOC2, and SMOC2 positivity was higher in old (p=0.001) and male (p<0.001) patients, and in well-differentiated GC (p<0.001). SMOC2 expression had a negative association with perineural invasion (p<0.001) and tumor stage (p<0.001). In survival analysis, SMOC2-positive GC patients had much better clinical outcomes in overall survival rates (p<0.001) compared to SMOC2-negative GC patients. The prognostic impact of SMOC2 remained significant both in intestinal (p<0.001) and diffuse-type GC (p<0.001). Remarkably, a multivariate analysis demonstrated SMOC2 as an independent prognostic marker [hazard ratio (HR)=0.732, p=0.045] along with venous invasion (p=0.012), tumor stage (p<0.001) and CDX2 (p=0.028).
Our results suggest that SMOC2 can be a prognostic marker for better clinical outcomes in GC.
背景/目的：富含半胱氨酸的酸性分泌蛋白 2（SMOC2）是一种分泌型细胞外基质蛋白，与细胞周期、血管生成和侵袭等癌症进展过程有关。本研究旨在检测 SMOC2 在各种胃病变中的表达情况，并评估其在大型胃癌（GC）患者队列中的预后价值。
采用实时定量 PCR 法检测 26 例新鲜冷冻 GC 样本中 SMOC2mRNA 的表达水平。通过组织微阵列免疫组化检测 SMOC2 蛋白的表达情况，该微阵列包括 734 例 GC 标本，评估其与临床病理特征及生存的相关性。
GC 组织中 SMOC2 的转录水平高于正常黏膜（p=0.006）。其表达水平与肠干细胞（ISC）标志物 LGR5 相关，但与 EPHB2 和 OLFM4 或候选癌干细胞标志物 CD133 和 CD44 无关。SMOC2 在肠上皮化生中表达显著增加，在胃腺瘤和早期胃癌（EGC）中进一步增加。总共有 34%的 GC 为 SMOC2 阳性，SMOC2 阳性与老年（p=0.001）和男性（p<0.001）患者以及分化良好的 GC（p<0.001）相关。SMOC2 的表达与神经周围浸润（p<0.001）和肿瘤分期（p<0.001）呈负相关。生存分析显示，SMOC2 阳性 GC 患者的总生存率（p<0.001）明显优于 SMOC2 阴性 GC 患者。在肠型（p<0.001）和弥漫型 GC（p<0.001）中，SMOC2 的预后影响仍然显著。值得注意的是，多变量分析表明 SMOC2 是独立的预后标志物[风险比（HR）=0.732，p=0.045]，与静脉浸润（p=0.012）、肿瘤分期（p<0.001）和 CDX2（p=0.028）相关。
我们的研究结果表明，SMOC2 可作为 GC 患者临床结局较好的预后标志物。
