Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282 Guangdong, China.
The First Clinical Medical School, Southern Medical University, 1023 Shatai South Road, Guangzhou, 510515 Guangdong, China.
Dis Markers. 2022 Dec 21;2022:8766448. doi: 10.1155/2022/8766448. eCollection 2022.
Platinum-based chemotherapy is the first choice of treatment for patients diagnosed with small lung cell cancer (SCLC). However, many patients exhibit resistance to it. Therefore, it is imperative to further investigate a prognostic biomarker indicating sensitivity to this therapy.
We collected and performed RNA sequencing on 45 SCLC samples from the Zhujiang Hospital (Local-SCLC). In addition, we used a public cohort from George et al. as a validation cohort (George-SCLC). The transforming growth factor signaling pathway (TGFB) activation status was determined according to the related ssGSEA score. We analyzed immune cell ratios, pathway activation scores, and immune-related genes in SCLC patients to further elucidate the potential mechanisms.
A high activation status of the TGFB pathway was associated with improved prognosis in SCLC patients receiving platinum-based chemotherapy (Local-SCLC: HR = 0.0238, (95% CI, 0.13-0.84), = 0.0238; George-SCLC: HR = 0.0315, (95% CI, 0.28-0.98), = 0.0315). Immune infiltration analysis showed that the TGFB-HIGH group had more M1 macrophages and Th1 cells, whilst fewer M2 macrophages, Th2 cells, and Treg cells were found in the Local-SCLC cohort. Mechanistic analysis showed that the TGBF-HIGH group was upregulated in STING-mediated immunity, apoptosis, and cell cycle arrest, as well as being downregulated in the process of DNA damage repair.
SCLC patients exhibiting a high activation status of the TGFB pathway demonstrate an improved prognosis with platinum-based chemotherapy. The potential underlying mechanism may be related to antitumor immune enhancement and DNA damage repair inhibition.
铂类化疗是小细胞肺癌（SCLC）患者的首选治疗方法。然而，许多患者对此治疗方法表现出耐药性。因此，迫切需要进一步研究一种预示对该治疗方法敏感性的预后生物标志物。
我们收集了来自珠江医院的 45 例 SCLC 样本并进行了 RNA 测序（Local-SCLC）。此外，我们使用了 George 等人的公共队列作为验证队列（George-SCLC）。根据相关 ssGSEA 评分确定转化生长因子 β 信号通路（TGFB）的激活状态。我们分析了 SCLC 患者的免疫细胞比例、通路激活评分和免疫相关基因，以进一步阐明潜在机制。
TGFB 通路的高激活状态与接受铂类化疗的 SCLC 患者的预后改善相关（Local-SCLC：HR = 0.0238，95%CI，0.13-0.84， = 0.0238；George-SCLC：HR = 0.0315，95%CI，0.28-0.98， = 0.0315）。免疫浸润分析显示，TGFB-HIGH 组中 M1 巨噬细胞和 Th1 细胞较多，而 Local-SCLC 队列中 M2 巨噬细胞、Th2 细胞和 Treg 细胞较少。机制分析表明，TGBF-HIGH 组在 STING 介导的免疫、细胞凋亡和细胞周期阻滞中上调，而在 DNA 损伤修复过程中下调。
TGFB 通路高激活状态的 SCLC 患者接受铂类化疗后预后改善。潜在的机制可能与抗肿瘤免疫增强和抑制 DNA 损伤修复有关。
