结直肠癌淋巴结中CEACAM5、KLK6、SLC35D3、MUC2和POSTN的qRT-PCR分析——一种改进的评估肿瘤分期和预后的方法。
qRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes-An improved method for assessment of tumor stage and prognosis.
发表日期:2023 Sep 12
作者:
Gudrun Lindmark, Lina Olsson, Basel Sitohy, Anne Israelsson, Joel Blomqvist, Sara Kero, Tamer Roshdy, Mattias Söderholm, Annamaria Turi, Jessica Isaksson, Thorbjörn Sakari, Michiel Dooper, George Dafnis, Pehr Forsberg, Susanne Skovsted, Maria Walldén, Chih-Han Kung, Martin Rutegård, Johanna Nordmyr, Måns Muhrbeck, Sten Hammarström, Marie-Louise Hammarström
来源:
INTERNATIONAL JOURNAL OF CANCER
摘要:
大约四分之一的结直肠癌患者在接受根治性手术后会复发,其中大多数会死亡。淋巴结(LN)转移是最重要的预后因子,也是决定术后治疗的关键因素。目前,LN转移通过组织病理学检查来确定,这是一种主观的方法,仅分析了少量的LN体积,并没有提供有关肿瘤侵袭性的信息。为了更好地确定有复发风险的患者,我们构建了一种qRT-PCR测试,称为ColoNode,用于确定CEACAM5、KLK6、SLC35D3、MUC2和POSTN mRNA的水平。这些生物标志物的组合估计了肿瘤细胞负荷和侵袭性,将患者分配到低(0,-1)、中等(1)、高(2)和非常高(3)复发风险的风险类别。在这里,我们展示了一项前瞻性、全国多中心研究的结果,包括8家医院的196名结肠癌患者。平均每个患者检查了21个淋巴结,总共4698个淋巴结,既通过组织病理学,又通过ColoNode进行了检查。随访3年后,有36名患者因结肠癌死亡或复发。ColoNode确定了所有被组织病理学检测到的患者,还额外确定了9名未被组织病理学检测到的患者。因此,25%的复发患者仅通过ColoNode被确定。多变量Cox回归分析证明ColoNode(1、2、3 vs 0、-1)是一个高度显著的风险因子,HR 4.24 [95%可信区间,1.42-12.69,P=0.01],而pTN分期(III vs I/II)失去了其单变量的显著性。总之,ColoNode通过确定更多未来复发的患者超过了组织病理学,将成为术后治疗决策的有价值工具。© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, -1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, -1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P = .01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.