Novel applications of histopathological markers to distinguish prognostic subgroups in colorectal adenocarcinoma

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. 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.本研究旨在通过对整体结直肠癌（Colorectal Cancer, CRC）患者亚组的预后标志物进行分层分析，探索组织学因素的全新应用场景。 我们回顾性收集了17项组织病理学与分子学特征，并采用Kaplan-Meier曲线分析及Cox回归检验，系统分析其在整体CRC患者及分层亚组中的预后预测价值；同时采用卡方（χ²）检验分析预后标志物与其他因素的相关性。 经分析，包括淋巴结转移（Lymph Node Metastasis, LNM）、神经/静脉侵犯（Perineural/Venous Invasion, PVI）、TNM分期、术后局部复发或远处转移（R/M），以及Ki-67表达与KRAS突变在内的组织病理学及分子标志物，被确定为整体CRC患者的独立预后生物标志物。 研究发现，LNM的预后差异在年龄、肿瘤部位、组织学分类（histo_classification）、细胞分化程度及KRAS/NRAS/BRAF（KNB）突变分层亚组中具有统计学意义；PVI在年龄、组织学分类、分化程度及R/M分层亚组中对患者生存的预测效果存在显著差异；与LNM和PVI一致，TNM分期在年龄、肿瘤部位、组织学分类、分化程度、R/M状态及KRAS/KNB突变分层亚组中同样表现出预后差异。 更重要的是，本研究首次证实，在年龄、组织学分类、LNM、TNM分期、Ki-67及KRAS/KNB突变分层亚组中，R/M并非不良预后因素。此外，本研究创新性发现KRAS突变在年龄、分化程度及LNM分层亚组中表现出预后差异。 本研究通过对CRC患者预后标志物的分层分析，揭示了上述组织病理学与分子标志物在临床中的全新应用价值，研究结果为未来精准病理学领域的研究提供了新的思路与视角。 LNM、PVI、TNM分期、R/M、组织学标志物Ki-67表达及分子标志物KRAS突变均为可独立预测CRC患者2年生存率的早期生物标志物。 组织病理学与分子标志物的预后差异普遍存在于年龄、肿瘤部位、分化程度、组织学类型、LNM、TNM分期及R/M分层的CRC亚组中。 LNM、PVI、TNM分期、R/M、组织学标志物Ki-67表达及分子标志物KRAS突变均为可独立预测CRC患者2年生存率的早期生物标志物。 组织病理学与分子标志物的预后差异普遍存在于年龄、肿瘤部位、分化程度、组织学类型、LNM、TNM分期及R/M分层的CRC亚组中。