Germline mutational profile of Chinese patients under 70 years old with colorectal cancer

Background:Inherited susceptibility accounts for nearly one-third of colorectal cancer(CRC)predispositions and has an 80%-100%lifetime risk of this disease.However,there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC.This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC,differences between Chinese and Western patients,and the phenotypegenotype correlation.Methods:We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing.A series of bioinformatic analyses,as well as statistical comparisons,were performed.Results:We found that 77 patients(14.6%)harbored functional variants of the 12 genes.The mutation frequencies of the top 5 mutated genes were 6.5%for MutL homolog 1(MLH1),5.1%for MutS homolog 2(MSH2),1.0%for MSH6,0.8%for PMS1 homolog 2(PMS2),and 0.8%for APC regulator of the WNT signaling pathway(APC).Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair(MMR)genes as compared with those in Western populations.Mutations in MLH1,MSH2,and MSH6 were found to be mutually exclusive.Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer(MLH1:20.6%vs.8.7%;MSH2:25.9%vs.8.6%)and family history of cancer than those without these mutations(MLH1:73.5%vs.48.4%;MSH2:70.4%vs.48.9%),and the lesions were more prone to occur on the right side of the colon than on the left side(MLH1:73.5%vs.29.3%;MSH2:56.0%vs.31.0%).The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations(70.6%vs.50.7%),and the rate of polyps was higher in patients withAPC mutations than in those with wild-type APC(75.0%vs.17.4%).Conclusion:These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.

体质量稳定及肠外营养特征与结直肠癌患者预后的相关性

背景:代谢紊乱及肠外营养(PN)特征对接受肠外营养的癌症患者生存的影响,目前所知有限。本研究旨在评估临床方法:研究纳入美国MD Anderson癌症中心2008-2013年接受肠外营养支持的572例结直肠癌患者。记录病例特征、体质指数、体质量、药物/手术治疗史、PN适应证、PN相关数据及生存情况。分析临床及PN特征与患者生存的相关性。结果:437例患者纳入最终分析,平均年龄57岁,81%为进展期结直肠癌。经多因素校正后,PN开始前体质量不稳定(变化≥2.5%)与生存负相关(HR=1.41,P=0.023)。肠梗阻作为PN适应证者较无肠梗者预后更差(HR=1.75,P=0.017)。PN配方中每千克理想体质量的氨基酸含量(g/kg)更高者,其生存时间更长(HR=0.59,P=0.029);而非PN配方中的静脉卡路里摄入量更高者,其生存时间更短(HR=1.04,P=0.011)。结论:体质指数和体质量稳定可能是预测接受PN支持的结直肠癌患者预后的有效营养学指标。制定PN计划时应考虑到非PN卡路里的摄入量,从而获得最佳的能量支持和能量平衡。进一步研究需明确PN配方中最优的氨基酸需求量和能量平衡。

Phosphorylated NFS1 weakens oxaliplatin-based chemosensitivity of colorectal cancer by preventing PANoptosis

Metabolic enzymes have an indispensable role in metabolic reprogramming,and their aberrant expression or activity has been associated with chemosensitivity.Hence,targeting metabolic enzymes remains an attractive approach for treating tumors.

包含奥沙利铂的辅助化疗可令术前放化疗后病理完全缓解的局部进展期直肠癌患者生存获益

背景:对于术前放化疗后获得病理完全缓解(pCR)的局部进展期直肠癌患者,术后辅助化疗的必要性仍不明确。本研究旨在探讨辅助化疗在这些患者中的治疗价值。方法:回顾性分析2008年-2014年间一家综合癌症中心连续收治的105例经术前放化疗后获得pCR的局部进展期直肠癌患者的临床资料。围手术期化疗采用包含奥沙利铂和卡培他滨的XELOX方案。比较术后加行辅助化疗与未行辅助化疗两组患者的无瘤生存和总体生存结果:83例(79.0%)例患者术后接受辅助化疗,22例(21.0%)未行辅助化疗。中位随访49月,辅助化疗组较未辅助化疗组3年无瘤生存率(92.8%vs.86.4%,P=0.029)和3年总生存率(95.1%vs.86.1%,P=0.026)显著提高。多因素分析显示,辅助化疗是无瘤生存的独立预后因素(HR=0.271,95%CI:0.0800.916),但对总体生存并无显著影响。亚组分析显示,对于年龄≤60岁的患者,辅助化疗的生存改善作用更为显著(HR=0.106,95%CI:0.0190.606;P=0.012)。结论:包含奥沙利铂的辅助化疗可以为pCR直肠癌患者带来生存获益,尤其是对于年轻患者。但其是否应常规用于pCR患者尚需进一步研究证实。