Shenzhen Nucleus Gene Technology Co., Ltd., Shenzhen, Guangdong, China.
Shenzhen Nucleus Huaxi Medical Laboratory, Shenzhen, Guangdong, China.
Aging (Albany NY). 2024 Aug 6;16(15):11606-11625. doi: 10.18632/aging.206041.
The intratumoral microorganisms participates in the progression and immunotherapy of colorectal cancer (CRC). However, due to technical limitations, the impact of microorganisms on CRC has not been fully understood. Therefore, we conducted a systematic analysis of relationship between bacterial lipopolysaccharide (LPS)-associated genes and immune cells to explore new biomarkers for predicting the prognosis of CRC.
The single-cell RNA sequencing data and the Comparative Toxicogenomics Database were used to screen T cells-associated LPS-related genes (TALRGs). Then, we established and validated the TALRGs risk signature in The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort and GSE39582 cohort. Besides, we compared the differences in tumor-infiltrating immune cell types, immunotherapeutic response, somatic mutation profiles, and tumor mutation burden (TMB) between high-risk group and low-risk group. In addition, the immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent was performed to explore the potential value of the TALRGs signature on immunotherapy.
Five prognostic TALRGs were identified and selected to build the prognostic model. The high-risk group had poor prognosis in both TCGA-COAD cohort ( < 0.0001) and GSE39582 cohort ( = 0.00019). The areas under the curves (AUCs) of TALRGs signature were calculated (TCGA-COAD cohort: 0.624 at 1 years, 0.639 at 3 years, 0.648 at 5 years; anti-PD-L1 cohort was 0.59). The high-risk group had advanced pathological stages and higher TMN stages in both TCGA-COAD cohort and GSE39582 cohort. The high-risk group had the higher infiltration of immunosuppressive cells, the expressions of immune checkpoint molecules, the IC50 values of chemotherapy drugs, and TP53 mutation rate ( < 0.05). In addition, patients with high TMB had worse prognosis ( < 0.05). Furthermore, the Imvigor210 also showed patients with high-risk scores had poor prognosis (platinum-treated cohort: = 0.0032; non-platinum-treated cohort: = 0.00017).
Microorganisms are closely related to the tumor microenvironment to influence the progression and immune response of CRC via stimulating T cells through LPS-related genes. The TALRGs signature contributed to predict the prognosis and immunotherapy of CRC, and became new therapeutic targets and biomarkers of CRC.
肿瘤内微生物参与结直肠癌（CRC）的进展和免疫治疗。然而，由于技术限制，微生物对 CRC 的影响尚未得到充分理解。因此，我们进行了一项系统分析，以探讨细菌脂多糖（LPS）相关基因与免疫细胞之间的关系，以期为 CRC 的预后预测寻找新的生物标志物。
利用单细胞 RNA 测序数据和比较毒理学基因组数据库筛选与 T 细胞相关的 LPS 相关基因（TALRGs）。然后，我们在 TCGA-COAD 队列和 GSE39582 队列中建立和验证了 TALRGs 风险特征。此外，我们比较了高危组和低危组之间肿瘤浸润免疫细胞类型、免疫治疗反应、体细胞突变谱和肿瘤突变负荷（TMB）的差异。此外，对接受抗 PD-L1 药物治疗的免疫治疗队列（Imvigor210）进行了分析，以探讨 TALRGs 特征在免疫治疗中的潜在价值。
确定了 5 个预后 TALRGs，并选择构建预后模型。高危组在 TCGA-COAD 队列（<0.0001）和 GSE39582 队列（=0.00019）中均具有较差的预后。TALRGs 特征的曲线下面积（AUC）计算结果（TCGA-COAD 队列：1 年时为 0.624，3 年时为 0.639，5 年时为 0.648；抗 PD-L1 队列为 0.59）。高危组在 TCGA-COAD 队列和 GSE39582 队列中均具有更晚期的病理分期和更高的 TNM 分期。高危组具有更高水平的免疫抑制细胞浸润、免疫检查点分子表达、化疗药物 IC50 值和 TP53 突变率（<0.05）。此外，高 TMB 患者的预后更差（<0.05）。此外，Imvigor210 还显示高危评分患者的预后较差（铂类治疗队列：=0.0032；非铂类治疗队列：=0.00017）。
微生物通过 LPS 相关基因刺激 T 细胞，与肿瘤微环境密切相关，影响 CRC 的进展和免疫反应。TALRGs 特征有助于预测 CRC 的预后和免疫治疗，成为 CRC 的新治疗靶点和生物标志物。
