■微卫星不稳定性高(MSI-H)是预测免疫检查点抑制剂(ICIs)在结直肠癌(CRC)患者中的作用的重要生物标志物。然而,由于MSI-H/缺失错配修复(dMMR)在总体人群中的突变率较低,一些医生认为,测试该指标会增加患者的负担,因此,一些患者无法接受最有益的治疗方法。为了为MSI-H比例较高的年轻患者提供测试标准,我们设计了这项回顾性对照研究.
■回顾性分析2017年1月至2019年12月郑州大学附属肿瘤医院收治的1,901例接受CRC相关基因检测的患者。对于这个分析,100名40岁或以下的患者被定义为年轻组,305名71岁及以上但小于80岁的患者被定义为老年组。我们纳入了符合以下标准的患者:(I)接受术前结肠镜检查或胃镜检查并诊断为CRC;(II)接受围手术期辅助治疗;(III)接受了CRC的治愈性手术。从手术时间到2023年4月30日或死亡,对每位患者进行随访。手术后的前2年,每3个月进行一次随访,此后每6个月。临床特征,如年龄,性别,体重指数(BMI),肿瘤深度(T),转移性淋巴结的数量(N),远处转移(M),肿瘤,节点,转移(TNM)分期,手术切除的范围,肿瘤大小,肿瘤位置,分化等级,收集癌胚抗原(CEA)水平。使用荧光原位杂交(FISH)分析微卫星不稳定性(MSI)状态。
■在年轻的CRC患者中,MSI-H的比例高于老年CRC患者(33%vs.10.16%,P<0.001)。与老年CRC患者相比,年轻CRC患者中低分化肿瘤的比例也较高(53%vs.31.15%,P<0.001)。然而,年轻和老年CRC患者的临床特征无显著差异.在预后方面,年轻组的生存分析表明,MSI状态[风险比(HR)=0.26,95%置信区间(CI):0.08-0.88,P=0.03],TNM分期(HR=3.84,95%CI:1.38-10.71,P=0.010)与CRC患者预后相关。
■与年龄较大的CRC患者相比,年轻的CRC患者MSI-H的突变率更高。我们的研究进一步证实了MSI-H可以作为CRC患者的有利预后标志物。这一发现可能为临床医生在预后评估和治疗选择方面提供有价值的指导。如果可行,我们希望可以对所有CRC患者进行MSI测试,以实现针对性测试,特别注意监测年轻患者的MSI状况。这将帮助临床医生为这些患者选择合适的治疗策略。
UNASSIGNED: Microsatellite instability-high (MSI-H) is an important biomarker for predicting the effects of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) patients. However, due to the low mutation rate of MSI-H/deficient mismatch repair (dMMR) in the overall population, some doctors are of the view that testing this indicator increases the burden on patients, and consequently some patients fail to receive the most beneficial treatment methods. In order to provide testing criteria for younger patients with a higher proportion of MSI-H, we designed this retrospective controlled study.
UNASSIGNED: A retrospective analysis was conducted of 1,901 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2017 to December 2019 and underwent CRC-related gene testing. For this analysis, 100 patients aged 40 or younger are defined as the young group, and 305 patients aged 71 and older but younger than 80 are defined as the elderly group. We included patients who met the following criteria: (I) underwent preoperative colonoscopy or gastroscopy and were diagnosed with CRC; (II) received perioperative adjuvant therapy; (III) underwent curative surgery for CRC. Each patient was followed up from the time of surgery until April 30, 2023, or death, with follow-up visits scheduled every 3 months for the first 2 years after surgery, and every 6 months thereafter. Clinical characteristics such as age, gender, body mass index (BMI), tumor depth (T), number of metastatic lymph nodes (N), distant metastasis (M), tumor, node, metastasis (TNM) stage, extent of surgical resection, tumor size, tumor location, differentiation grade, and carcinoembryonic antigen (CEA) levels were collected. The microsatellite instability (MSI) status was analyzed using fluorescence in situ hybridization (FISH).
UNASSIGNED: In young CRC patients, the proportion of MSI-H is higher than in elderly CRC patients (33% vs. 10.16%, P<0.001). The proportion of poorly differentiated tumors is also higher in young CRC patients compared to elderly CRC patients (53% vs. 31.15%, P<0.001). However, there were no significant differences in clinical characteristics between young and elderly CRC patients. In terms of prognosis, survival analysis of the young group showed that MSI status [hazard ratio (HR) =0.26, 95% confidence interval (CI): 0.08-0.88, P=0.03], TNM staging (HR =3.84, 95% CI: 1.38-10.71, P=0.010) were associated with the prognosis of CRC patients.
UNASSIGNED: The mutation rate of MSI-H is higher in young CRC patients compared to older. Our study further confirms that MSI-H can serve as a favorable prognostic marker for CRC patients. This finding may provide valuable guidance for clinicians in terms of prognosis assessment and treatment selection. If feasible, we hope that MSI testing can be performed for all CRC patients to enable targeted testing, with particular attention to monitoring the MSI status in young patients. This will aid clinicians in selecting appropriate treatment strategies for these patients.