Phipps Amanda I, Hill Courtney M, Lin Genevieve, Malen Rachel C, Reedy Adriana M, Kahsai Orsalem, Ammar Hamza, Curtis Keith, Ma Ningxin, Randolph Timothy W, Ma Jing, Ogino Shuji, Newcomb Polly A, Hullar Meredith Aj
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Department of Epidemiology, University of Washington, Seattle, Washington.
Gastro Hep Adv. 2025 Feb 20;4(6):100644. doi: 10.1016/j.gastha.2025.100644. eCollection 2025.
() is linked to colorectal cancer (CRC) etiology and survival. We hypothesized that CRC tumor attributes and survival are associated with the amount and presence of in tumors.
abundance was measured via droplet digital polymerase chain reaction in patient-matched CRC tumor and normal tissue samples from 859 Puget Sound CRC Cohort participants. enrichment was defined as the continuous difference in normalized abundance between patient-matched tumor and normal tissue samples. presence in tumor was classified categorically as not present, low, or high, regardless of status in matched normal tissue. Associations of enrichment and presence with tumor site, stage, DNA mismatch repair (MMR) status, CpG island methylator phenotype (CIMP) status, and mutation status, and molecular subtypes based on combinations of tumor markers were assessed using logistic regression. Associations of enrichment and presence with CRC survival was estimate with Cox regression.
was present in 20% of tumor tissues and 10% of normal tissues, with higher average abundance in tumors. High presence was independently associated with deficient MMR (dMMR) status and in the context of molecular subtypes for type 1 tumors (dMMR, CIMP-high, -mutated) and type 5 tumors (dMMR, CIMP-low or negative, -wildtype). enrichment was associated with type 5 and type 2 tumors (proficient MMR, CIMP-high, -mutated). enrichment and presence were associated with poorer CRC survival, with some suggestion that associations differed by MMR status.
Detectable in CRC tissue is associated with certain CRC tumor attributes and survival; however, associations may vary based on definition.
（）与结直肠癌（CRC）的病因及生存情况相关。我们推测CRC肿瘤特征及生存情况与肿瘤中（）的含量及存在情况有关。
通过液滴数字聚合酶链反应对来自859名普吉特海湾CRC队列参与者的患者匹配的CRC肿瘤和正常组织样本中的（）丰度进行测量。（）富集定义为患者匹配的肿瘤和正常组织样本之间标准化丰度的持续差异。肿瘤中（）的存在情况根据匹配正常组织中的（）状态分类为不存在、低或高。使用逻辑回归评估（）富集和存在情况与肿瘤部位、分期、DNA错配修复（MMR）状态、CpG岛甲基化表型（CIMP）状态、（）和（）突变状态以及基于肿瘤标志物组合的分子亚型之间的关联。使用Cox回归估计（）富集和存在情况与CRC生存的关联。
20%的肿瘤组织和10%的正常组织中存在（），肿瘤中的平均丰度更高。高（）存在情况与MMR缺陷（dMMR）状态独立相关，并且在1型肿瘤（dMMR、CIMP高、（）突变）和5型肿瘤（dMMR、CIMP低或阴性、（）野生型）的分子亚型背景下也是如此。（）富集与5型和2型肿瘤（MMR熟练、CIMP高、（）突变）相关。（）富集和存在情况与较差的CRC生存相关，有一些迹象表明这种关联因MMR状态而异。
CRC组织中可检测到的（）与某些CRC肿瘤特征及生存情况相关；然而，关联可能因（）定义的不同而有所差异。
