Wu Tong, Fang Lin, Ruan Yuli, Shi Mengde, Su Dan, Ma Yue, Ma Ming, Wang Bojun, Liao Yuanyu, Han Shuling, Lu Xiaolin, Zhang Chunhui, Liu Chao, Zhang Yanqiao
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150001, People's Republic of China.
Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin, China.
J Transl Med. 2025 Jan 22;23(1):107. doi: 10.1186/s12967-025-06141-x.
Although the TNM staging system plays a critical role in guiding adjuvant chemotherapy for colorectal cancer (CRC), its precision for risk stratification in stage II and III CRC patients with proficient DNA mismatch repair (pMMR) remains limited. Therefore, precise predictive models and research on postoperative treatments are crucial for enhancing patient survival and improving quality of life.
This retrospective study analyzed 1051 pMMR CRC patients who underwent radical resection and were randomly assigned to training (n = 736) and validation (n = 315) groups. Immunohistochemistry and hematoxylin and eosin staining were utilized to evaluate regulatory-Immunoscore (RIS), tertiary lymphoid structures (TLS), and tumor budding (TB). The Tumor Aggression-Defense Index (TADI) was derived through a multi-factor COX regression model. Subgroup analysis demonstrated potential of TADI in guiding personalized adjuvant therapy for stage II and III CRC.
Univariate and multivariate Cox analysis indicated that TADI was an independent prognostic indicator. Among stage II CRC, chemotherapy was significantly correlated with improved recurrence times in individuals with intermediate (95% CI 0.19-0.59, P < 0.001) and high (95% CI 0.36-0.95, P = 0.031) TADI. In stage III CRC receiving adjuvant chemotherapy, a duration of 3 months or longer was notably associated with a prolonged time to recurrence in those with high TADI (95% CI 0.40-0.98, P = 0.041) compared to durations of less than 3 months.
The TADI serves as an effective parameter for predicting the survival outcomes of stage I-III pMMR CRC patients and guiding precision treatment strategies.
尽管TNM分期系统在指导结直肠癌（CRC）辅助化疗中起着关键作用，但其在错配修复功能正常（pMMR）的II期和III期CRC患者风险分层中的精确性仍然有限。因此，精确的预测模型和术后治疗研究对于提高患者生存率和改善生活质量至关重要。
这项回顾性研究分析了1051例行根治性切除的pMMR CRC患者，这些患者被随机分为训练组（n = 736）和验证组（n = 315）。采用免疫组织化学和苏木精-伊红染色评估调节性免疫评分（RIS）、三级淋巴结构（TLS）和肿瘤芽生（TB）。通过多因素COX回归模型得出肿瘤侵袭-防御指数（TADI）。亚组分析显示TADI在指导II期和III期CRC个体化辅助治疗方面具有潜力。
单因素和多因素Cox分析表明，TADI是一个独立的预后指标。在II期CRC中，化疗与TADI中等（95%CI 0.19-0.59，P < 0.001）和高（95%CI 0.36-0.95，P = 0.031）的患者复发时间改善显著相关。在接受辅助化疗的III期CRC中，与化疗时间少于3个月相比，化疗时间3个月或更长与TADI高的患者复发时间延长显著相关（95%CI 0.40-0.98, P = 0.041）。
TADI是预测I-III期pMMR CRC患者生存结局和指导精准治疗策略的有效参数。
