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Abstract：
BACKGROUND: Tertiary lymphoid structures (TLS) are the lymphocyte aggregates that play a key role in the vast majority of solid tumors including colon cancer, displaying an antitumor effect under most circumstances. The heterogeneity between left- and right-sided colon cancer (LCC and RCC) encompasses various aspects, such as clinical manifestations, pathological features, and immune responses. However, the function and prognostic significance of TLS within LCC and RCC have yet to be fully understood.
METHODS: A retrospective analysis was performed on 2612 patients who underwent radical resection for LCC or RCC without distant metastasis in multiple medical centers. Utilizing propensity score matching, 121 patients with LCC and 121 patients with RCC were selected for the training set. An external validation set including 64 patients with LCC and 64 patients with RCC were also employed. Hematoxylin-eosin and immunohistochemical staining were used to assess TLS and the proportion of various immune cells. Clinical characteristics and prognostic values of TLS in patients with LCC and RCC were analyzed. Nomograms were constructed for LCC and RCC to predict 3-year and 5-year overall survival (OS), respectively.
RESULTS: For LCC and RCC patients, TLS was located in the interstitial region or outside the tumor tissue and mainly consisted of B cells and T cells. The TLS quantity and density in RCC were higher than those of LCC. In multivariate Cox regression analysis, TLS density ( P =0.014), vascular invasion ( P =0.019), and AJCC stage ( P =0.026) were independent prognostic factors for 5-year OS of RCC. For LCC patients, AJCC stage ( P =0.024), tumor differentiation ( P =0.001), and tumor budding ( P =0.040) emerged as independent prognostic factors for 5-year OS. Similar results were obtained in the external verification set. Separate nomograms for RCC and LCC were developed, displaying improved prediction performance compared to the AJCC 8th edition TNM staging system.
CONCLUSIONS: Differences in TLS quantity and density were observed between LCC and RCC, suggesting that a nomogram based on TLS density could more effectively predict survival for RCC patients. Furthermore, a nomogram based on tumor budding was recommended for better prediction of LCC patient survival. Taken together, these results suggested that the immune and clinical characteristics of colon cancer at left and right side were substantially different, which may lead to the use of different prediction model and the development of individual treatment strategy.
METHODS: A retrospective analysis was performed on 2612 patients who underwent radical resection for LCC or RCC without distant metastasis in multiple medical centers. Utilizing propensity score matching, 121 patients with LCC and 121 patients with RCC were selected for the training set. An external validation set including 64 patients with LCC and 64 patients with RCC were also employed. Hematoxylin-eosin and immunohistochemical staining were used to assess TLS and the proportion of various immune cells. Clinical characteristics and prognostic values of TLS in patients with LCC and RCC were analyzed. Nomograms were constructed for LCC and RCC to predict 3-year and 5-year overall survival (OS), respectively.
RESULTS: For LCC and RCC patients, TLS was located in the interstitial region or outside the tumor tissue and mainly consisted of B cells and T cells. The TLS quantity and density in RCC were higher than those of LCC. In multivariate Cox regression analysis, TLS density ( P =0.014), vascular invasion ( P =0.019), and AJCC stage ( P =0.026) were independent prognostic factors for 5-year OS of RCC. For LCC patients, AJCC stage ( P =0.024), tumor differentiation ( P =0.001), and tumor budding ( P =0.040) emerged as independent prognostic factors for 5-year OS. Similar results were obtained in the external verification set. Separate nomograms for RCC and LCC were developed, displaying improved prediction performance compared to the AJCC 8th edition TNM staging system.
CONCLUSIONS: Differences in TLS quantity and density were observed between LCC and RCC, suggesting that a nomogram based on TLS density could more effectively predict survival for RCC patients. Furthermore, a nomogram based on tumor budding was recommended for better prediction of LCC patient survival. Taken together, these results suggested that the immune and clinical characteristics of colon cancer at left and right side were substantially different, which may lead to the use of different prediction model and the development of individual treatment strategy.
摘要：
背景：三级淋巴结构（TLS）是淋巴细胞聚集体，在包括结肠癌在内的绝大多数实体瘤中起关键作用，在大多数情况下显示抗肿瘤效果。左侧和右侧结肠癌（LCC和RCC）之间的异质性包括各个方面，如临床表现，病理特征,和免疫反应。然而,TLS在LCC和RCC中的功能和预后意义尚未完全了解。
方法：对在多个医疗中心接受LCC或RCC根治术但无远处转移的2612例患者进行回顾性分析。利用倾向得分匹配，选择121例LCC患者和121例RCC患者作为训练组。还采用了包括64名LCC患者和64名RCC患者的外部验证集。使用苏木精-伊红(H&E)和免疫组织化学(IHC)染色来评估TLS和各种免疫细胞的比例。分析LCC和RCC患者TLS的临床特征及预后价值。为LCC和RCC构建了列线图，以预测3年和5年总生存期（OS）。分别。
结果：对于LCC和RCC患者，TLS位于间质区或肿瘤组织外部，主要由B细胞和T细胞组成。RCC的TLS数量和密度均高于LCC。在多元Cox回归分析中，TLS密度（P=0.014），血管侵犯(P=0.019)和AJCC分期(P=0.026)是影响RCC患者5年OS的独立预后因素。对于LCC患者，AJCC阶段（P=0.024），肿瘤分化（P=0.001），肿瘤出芽（P=0.040）是5年OS的独立预后因素。在外部验证集中获得了类似的结果。开发了RCC和LCC的单独列线图，显示与AJCC第8版TNM暂存系统相比改进的预测性能。
结论：在LCC和RCC之间观察到TLS数量和密度的差异，提示基于TLS密度的列线图可以更有效地预测RCC患者的生存率。此外，建议使用基于肿瘤出芽的列线图,以更好地预测LCC患者的生存率.一起来看,这些结果表明，左右两侧结肠癌的免疫和临床特征有很大不同，这可能导致不同预测模型的使用和个性化治疗策略的制定。
方法：对在多个医疗中心接受LCC或RCC根治术但无远处转移的2612例患者进行回顾性分析。利用倾向得分匹配，选择121例LCC患者和121例RCC患者作为训练组。还采用了包括64名LCC患者和64名RCC患者的外部验证集。使用苏木精-伊红(H&E)和免疫组织化学(IHC)染色来评估TLS和各种免疫细胞的比例。分析LCC和RCC患者TLS的临床特征及预后价值。为LCC和RCC构建了列线图，以预测3年和5年总生存期（OS）。分别。
结果：对于LCC和RCC患者，TLS位于间质区或肿瘤组织外部，主要由B细胞和T细胞组成。RCC的TLS数量和密度均高于LCC。在多元Cox回归分析中，TLS密度（P=0.014），血管侵犯(P=0.019)和AJCC分期(P=0.026)是影响RCC患者5年OS的独立预后因素。对于LCC患者，AJCC阶段（P=0.024），肿瘤分化（P=0.001），肿瘤出芽（P=0.040）是5年OS的独立预后因素。在外部验证集中获得了类似的结果。开发了RCC和LCC的单独列线图，显示与AJCC第8版TNM暂存系统相比改进的预测性能。
结论：在LCC和RCC之间观察到TLS数量和密度的差异，提示基于TLS密度的列线图可以更有效地预测RCC患者的生存率。此外，建议使用基于肿瘤出芽的列线图,以更好地预测LCC患者的生存率.一起来看,这些结果表明，左右两侧结肠癌的免疫和临床特征有很大不同，这可能导致不同预测模型的使用和个性化治疗策略的制定。
