Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Research Programs Unit, Translational Cancer Medicine, University of Helsinki, Helsinki, Finland.
BMC Gastroenterol. 2021 Sep 4;21(1):341. doi: 10.1186/s12876-021-01918-y.
Colon cancer (CC) is one of the most commonly diagnosed malignancies worldwide. Several biomarkers have been suggested for improved prognostic evaluation, but few have been implemented in clinical practice. There is a need for biomarkers that predict the tumor behavior in CC and allow stratification of patients that would benefit from adjuvant therapy. We recently identified and functionally characterized a previously unknown protein that we called ASTROPRINCIN (APCN) due to its abundance in astrocytes. APCN, also annotated as FAM171A1, is found in trophoblasts of early placenta. We demonstrated that high expression levels of APCN in cancer cells induced motility and ability of invasive growth in semisolid medium.
We screened by immunohistochemistry a tissue microarray material from the tumors of 429 CC patients with clinical follow-up in a test series and 255 CC patients in a validation series.
We showed that low or absent APCN expression correlates with a favorable prognosis while high APCN expression was a sign of an adverse outcome. Cox uni- and multivariable analysis revealed that elevated tumor expression of APCN constitutes a robust marker of poor prognosis independent of stage, grade, patient's age, or gender.
Our findings demonstrate that APCN is a novel independent prognostic marker in CC and could potentially select patients for more intense postoperative adjuvant treatment and follow-up.
结肠癌（CC）是全球最常见的恶性肿瘤之一。已经提出了几种生物标志物用于改善预后评估，但很少有标志物被应用于临床实践。我们需要能够预测 CC 肿瘤行为并能够对接受辅助治疗将获益的患者进行分层的生物标志物。我们最近发现并对一种以前未知的蛋白进行了功能鉴定，因其在星形胶质细胞中丰度高，我们将其命名为 ASTROPRINCIN（APCN）。APCN 也被注释为 FAM171A1，存在于早期胎盘的滋养细胞中。我们证明，癌细胞中 APCN 的高表达水平可诱导细胞的运动性和在半固体培养基中的侵袭生长能力。
我们通过免疫组织化学筛选了来自 429 例 CC 患者的组织微阵列材料，这些患者在测试系列中有临床随访，在验证系列中有 255 例 CC 患者。
我们发现低或无 APCN 表达与预后良好相关，而 APCN 高表达是不良预后的标志。Cox 单变量和多变量分析表明，肿瘤 APCN 表达升高是独立于分期、分级、患者年龄或性别等因素的预后不良的有力标志物。
我们的研究结果表明，APCN 是 CC 的一种新的独立预后标志物，可能能够选择需要更强化术后辅助治疗和随访的患者。
