Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Gynecology, Obstetrics & Gynecology, Hospital of Fudan University, Fudan University, Shanghai, China.
Gynecol Oncol. 2023 Aug;175:133-141. doi: 10.1016/j.ygyno.2023.05.071. Epub 2023 Jun 23.
Squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix have distinct biological behaviors and different treatment responses. Studies on immune features and genomic profiling of these two pathologic types were limited and mainly focused on small patient cohorts.
From 2014 to 2021, 336 (254 SCC vs. 82 AC) cervical cancer patients who were diagnosed/treated in 7 medical centers in China were enrolled in the study. Next-generation sequencing of 425 cancer-relevant genes was performed on tumor tissues and liquid biopsies. Somatic alterations and immune response-related biomarkers were analyzed. Patient prognosis and immune infiltration were analyzed using data from The Cancer Genome Atlas (TCGA).
AC tended to have more immunotherapy resistance-related STK11 alterations (P = 0.039), a higher proportion of microsatellite instability (P = 0.21), and more actionable mutations (P = 0.161). In contrast, higher tumor mutational burdens (TMB; P = 0.01), a higher proportion of TMB-high patients (P = 0.016), and more PD-L1-high patients (P = 0.0013) were observed in SCC. Multiple genetic alterations and aberrant signaling pathways were specifically enriched in AC (e.g., TP53, KRAS, ERBB2, and ARID1A alterations) or SCC (e.g., PIK3CA, FBXW7, EP300, and BAP1 mutations). Notably, AC-enriched genetic changes were significantly associated with decreased infiltrations of various B cells, T cells, and dendritic cells, whereas SCC-associated molecular features tended to be associated with increased CD4+ T cell infiltrations.
This was the first multi-center study revealing the immunologic and genomic features between SCC and AC in Chinese patients with cervical cancer. Our findings have illustrated the difference in genetic profiles of those two cervical cancer subtypes, which may suggest the possibility of differential treatment regimens, with better immunotherapy efficacy in SCC and targeted therapy options more favorable in AC.
宫颈鳞状细胞癌（SCC）和腺癌（AC）具有不同的生物学行为和治疗反应。关于这两种病理类型的免疫特征和基因组分析的研究有限，主要集中在小患者队列中。
本研究纳入了 2014 年至 2021 年间在中国 7 家医疗中心诊断/治疗的 336 例宫颈癌患者（254 例 SCC 与 82 例 AC）。对肿瘤组织和液体活检标本进行了 425 个癌症相关基因的下一代测序。分析了体细胞改变和免疫反应相关的生物标志物。使用癌症基因组图谱（TCGA）的数据分析了患者的预后和免疫浸润情况。
AC 倾向于具有更多免疫治疗耐药相关 STK11 改变（P=0.039），更高的微卫星不稳定比例（P=0.21）和更多的可操作突变（P=0.161）。相比之下，SCC 中观察到更高的肿瘤突变负荷（TMB；P=0.01）、更高比例的 TMB-高患者（P=0.016）和更多的 PD-L1-高患者（P=0.0013）。特定的基因改变和异常信号通路在 AC（如 TP53、KRAS、ERBB2 和 ARID1A 改变）或 SCC（如 PIK3CA、FBXW7、EP300 和 BAP1 突变）中特异性富集。值得注意的是，AC 富集的遗传变化与各种 B 细胞、T 细胞和树突状细胞浸润减少显著相关，而 SCC 相关的分子特征则与 CD4+T 细胞浸润增加相关。
这是第一项多中心研究，揭示了中国宫颈癌患者 SCC 和 AC 之间的免疫学和基因组特征。我们的研究结果说明了这两种宫颈癌亚型的遗传特征的差异，这可能提示了不同治疗方案的可能性，SCC 可能更适合免疫治疗，而 AC 可能更适合靶向治疗。
