■通过对所有亚组CRC患者的预后标志物进行分层,探索组织学因素的新应用。
■采用Kaplan-Meier曲线分析和Cox回归检验,回顾性收集并系统分析了17种组织病理学和分子学因素,以预测总体和分层亚组的CRC预后。采用χ2检验分析预后标志物与其他因素的相关性。
■包括淋巴结转移(LNM)在内的组织病理学标志物,神经周/静脉侵犯(PVI),TNM阶段,手术后局部复发或远处转移(R/M)和分子标志物Ki-67表达以及KRAS突变被确定为整体CRC的独立预后生物标志物.发现LNM的差异预后在年龄上是显着的,肿瘤部位,组织学分类(histo_分类),细胞分化,和KRAS/NRAS/BRAF(KNB)突变分层亚组。发现PVI可以不同程度地预测患者的年龄生存率,histo_分类,分化,和R/M分层亚组。与LNM和PVI相同,还发现TNM在年龄方面表现出不同的预后,肿瘤部位,histo_分类,分化,R/M状态和KRAS/KNB突变分层亚组。更重要的是,R/M首先被认为对年龄的患者来说并不可怕,histo_分类,LNM,TNM,Ki-67和KRAS/KNB分层亚组。此外,创新发现KRAS突变在年龄上显示出不同的预后,分化,和LNM分层亚组。
■CRC患者预后标志物的分层分析表明,上述组织病理学和分子标志物在临床上的新应用,这些发现为未来的精确病理学研究提供了新的见解。
病理标志物LNM,PVI,TNM阶段,R/M,组织学标志物Ki-67表达和分子标志物KRAS突变都是能够独立预测CRC2年生存率的早期生物标志物.组织病理学和分子标志物的差异预后常见于年龄,肿瘤部位,分化,组织学类型,LNM,TNM,和R/M分层CRC亚组。
To explore the novel applications of histological factors by stratifying the prognostic markers of the overall CRC patients in subgroups.
A total of 17 histopathological and molecular factors were retrospectively collected and systematically analyzed for the prediction of CRC prognosis in the overall and stratified subgroups by using the Kaplan-Meier curve analysis as well as the Cox regression test. The χ2 test was used to analyze the correlation of the prognostic markers with other factors.
The histopathological markers including the lymph node metastasis (LNM), perineural/venous invasion (PVI), TNM stage, the local recurrence or distant metastasis after surgery (R/M) and the molecular markers Ki-67 expression as well as KRAS mutation were identified to be the independent prognostic biomarkers in the overall CRC. The differential prognosis of LNM was found to be significant in age, tumor site, histological classification (histo_classification), cell differentiation, and KRAS/NRAS/BRAF (KNB) mutation stratified subgroups. The PVI was discovered to differently predict survival for patients in age, histo_classification, differentiation, and R/M stratified subgroups. Same as LNM and PVI, TNM was also found to demonstrate differential prognosis in age, tumor site, histo_classification, differentiation, R/M status and KRAS/KNB mutation stratified subgroups. More importantly, R/M was firstly identified not to be terrible for patients in age, histo_classification, LNM, TNM, Ki-67, and KRAS/KNB stratified subgroups. Besides, KRAS mutation was innovatively found to show differential prognosis in age, differentiation, and LNM stratified subgroups.
The stratification analyses of prognostic markers in CRC patients indicate novel applications of the above histopathological and molecular markers in clinic and the findings provide new insights into future investigations of precision pathology.
The pathological markers LNM, PVI, TNM stage, R/M, the histological marker Ki-67 expression and the molecular marker KRAS mutation are all the early biomarkers capable of independently predicting the 2-year survival rate for CRC.Differential prognosis of the histopathological and molecular markers is commonly found in age, tumor site, differentiation, histological type, LNM, TNM, and R/M stratified CRC subgroups.