You Dingyun, Zhang Shuai, Yan Shan, Ding Yingying, Li Chunxia, Cheng Xianshuo, Wu Lin, Wang Weizhou, Zhang Tao, Li Zhenhui, He Yongwen
Department of Dental Research, The Affiliated Stomatological Hospital of Kunming Medical University, Kunming, China.
Yunnan Key Laboratory of Stomatology, Kunming Medical University, Kunming, China.
Front Oncol. 2022 Aug 1;12:939982. doi: 10.3389/fonc.2022.939982. eCollection 2022.
The identification of high-risk population patients is key to the personalized treatment options for the stage II colorectal cancers. The use of proteomics in the prognosis of patients with stage II colorectal cancer remains unclear.
Using quantitative proteomics, we analyzed proteins that are differentially expressed in the tumor and adjacent normal tissues of 11 paired colorectal cancer patients with and without recurrence selected by a nested case-control design. Of the 21 identified proteins, we selected one candidate protein. The association of the corresponding gene of the selected protein with overall survival (OS) and adjuvant chemotherapy was analyzed using two independent cohorts of patients with stages II colorectal cancer.
Sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) was selected as the candidate biomarker. A group of 124 patients (12.5%) were stratified into SAMHD1-high subgroup. The 5-year OS rate of SAMHD1-high patients was lower than that of SAMHD1-low patients with stage II colorectal cancer (discovery cohort: hazard ratio [HR] = 2.89, 95% confidence interval [CI], 1.17-7.18, = 0.016; validation cohort: HR = 2.25, 95% CI, 1.17-4.34, = 0.013). The Cox multivariate analysis yielded similar results. In a pooled database, the 5-year OS rate was significantly different between patients with and without adjuvant chemotherapy among stage II SAMHD1-low tumors than in patients with stage II SAMHD1-high tumors (88% vs. 77%, = 0.032).
SAMHD1-high expression could help in identifying patients with stage II colorectal cancer with poor prognosis and less benefit from adjuvant chemotherapy.
识别高危人群患者是II期结直肠癌个体化治疗方案的关键。蛋白质组学在II期结直肠癌患者预后中的应用仍不明确。
采用定量蛋白质组学，我们分析了11对通过巢式病例对照设计选择的有或无复发的结直肠癌患者的肿瘤组织和相邻正常组织中差异表达的蛋白质。在鉴定出的21种蛋白质中，我们选择了一种候选蛋白质。使用两个独立的II期结直肠癌患者队列分析所选蛋白质的相应基因与总生存期（OS）和辅助化疗的关联。
无菌α基序和含组氨酸-天冬氨酸结构域蛋白1（SAMHD1）被选为候选生物标志物。124名患者（12.5%）被分层到SAMHD1高表达亚组。II期结直肠癌患者中，SAMHD1高表达患者的5年总生存率低于SAMHD1低表达患者（发现队列：风险比[HR]=2.89，95%置信区间[CI]，1.17 - 7.18，P = 0.016；验证队列：HR = 2.25，95% CI，1.17 - 4.34，P = 0.013）。Cox多变量分析得出了类似结果。在一个汇总数据库中，II期SAMHD1低表达肿瘤患者中接受和未接受辅助化疗的患者5年总生存率差异显著，而II期SAMHD1高表达肿瘤患者中则不然（88%对77%，P = 0.032）。
SAMHD1高表达有助于识别II期结直肠癌预后不良且辅助化疗获益较少的患者。
