PDF(Pubmed)
Abstract：
UNASSIGNED: Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear.
UNASSIGNED: We employed an RNA-sequencing cohort (n = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA-BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape.
UNASSIGNED: In our study, chitinase 3-like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P < 0.001). Within UCB tissues, CHI3L1 was expressed in both stromal cells (52.8%) and tumor cells (7.3%). Moreover, CHI3L1+ stromal cells, but not tumor cells, exhibited independent prognostic significance for both overall survival (P < 0.001) and recurrence-free survival (P = 0.006). CHI3L1+ stromal cells were positively associated with D2-40+ lymphatic vessel density (P < 0.001) and the immunosuppressive PD-L1/PD-1/CD8 axis in UCB tissues (all P < 0.05). A bioinformatics analysis also identified a positive association between CHI3L1 expression and lymphangiogenesis or immunosuppression pathways.
UNASSIGNED: Our study established a clear association between stromal CHI3L1 expression and lymphatic metastasis, suggesting that stromal CHI3L1 expression is a potential prognostic marker for bladder cancer patients.
UNASSIGNED: We employed an RNA-sequencing cohort (n = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA-BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape.
UNASSIGNED: In our study, chitinase 3-like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P < 0.001). Within UCB tissues, CHI3L1 was expressed in both stromal cells (52.8%) and tumor cells (7.3%). Moreover, CHI3L1+ stromal cells, but not tumor cells, exhibited independent prognostic significance for both overall survival (P < 0.001) and recurrence-free survival (P = 0.006). CHI3L1+ stromal cells were positively associated with D2-40+ lymphatic vessel density (P < 0.001) and the immunosuppressive PD-L1/PD-1/CD8 axis in UCB tissues (all P < 0.05). A bioinformatics analysis also identified a positive association between CHI3L1 expression and lymphangiogenesis or immunosuppression pathways.
UNASSIGNED: Our study established a clear association between stromal CHI3L1 expression and lymphatic metastasis, suggesting that stromal CHI3L1 expression is a potential prognostic marker for bladder cancer patients.
摘要：
■淋巴转移，转移过程的早期阶段，与膀胱尿路上皮癌（UCB）的不良临床结局有关。然而,炎症在引发淋巴转移中的作用尚不清楚.
■我们采用了来自孙中山纪念医院（SYMH）的RNA测序队列（n=50）来鉴定与淋巴转移相关的最高度上调的炎症基因。使用免疫组织化学和免疫荧光分析，我们在来自SYMH的独立UCB队列(n=244)中验证了鉴定的分子与临床特征和预后的关联.我们还分析了TCGA-BLCA队列（n=408），以确定其潜在的生物学途径和免疫前景。
■在我们的研究中，几丁质酶3样1（CHI3L1）在有淋巴转移的UCB组织中作为明显过表达的促炎介质出现（81.1％vs.47.8%,P<0.001)。在UCB组织内，CHI3L1在基质细胞(52.8%)和肿瘤细胞(7.3%)中均有表达。此外，CHI3L1+基质细胞，但不是肿瘤细胞，对总生存期(P<0.001)和无复发生存期(P=0.006)均有独立的预后意义.CHI3L1+基质细胞与D2-40+淋巴管密度呈正相关（P<0.001），UCB组织中免疫抑制PD-L1/PD-1/CD8轴呈正相关（均P<0.05）。生物信息学分析还确定了CHI3L1表达与淋巴管生成或免疫抑制途径之间的正相关。
■我们的研究建立了基质CHI3L1表达与淋巴转移之间的明确关联，表明基质CHI3L1表达是膀胱癌患者的潜在预后指标。
■我们采用了来自孙中山纪念医院（SYMH）的RNA测序队列（n=50）来鉴定与淋巴转移相关的最高度上调的炎症基因。使用免疫组织化学和免疫荧光分析，我们在来自SYMH的独立UCB队列(n=244)中验证了鉴定的分子与临床特征和预后的关联.我们还分析了TCGA-BLCA队列（n=408），以确定其潜在的生物学途径和免疫前景。
■在我们的研究中，几丁质酶3样1（CHI3L1）在有淋巴转移的UCB组织中作为明显过表达的促炎介质出现（81.1％vs.47.8%,P<0.001)。在UCB组织内，CHI3L1在基质细胞(52.8%)和肿瘤细胞(7.3%)中均有表达。此外，CHI3L1+基质细胞，但不是肿瘤细胞，对总生存期(P<0.001)和无复发生存期(P=0.006)均有独立的预后意义.CHI3L1+基质细胞与D2-40+淋巴管密度呈正相关（P<0.001），UCB组织中免疫抑制PD-L1/PD-1/CD8轴呈正相关（均P<0.05）。生物信息学分析还确定了CHI3L1表达与淋巴管生成或免疫抑制途径之间的正相关。
■我们的研究建立了基质CHI3L1表达与淋巴转移之间的明确关联，表明基质CHI3L1表达是膀胱癌患者的潜在预后指标。
