Integrated single-cell transcriptome analysis of the tumor ecosystems underlying cervical cancer metastasis

Abstract

Cervical cancer (CC) is one of the most frequent female malignancies worldwide. However, the molecular mechanism of lymph node metastasis in CC remains unclear. In this study, we investigated the transcriptome profile of 51,507 single cells from primary tumors, positive lymph nodes (P-LN), and negative lymph nodes (N-LN) using single-cell sequencing. Validation experiments were performed using bulk transcriptomic datasets and immunohistochemical assays. Our results indicated that epithelial cells in metastatic LN were associated with cell- cycle-related signaling pathways, such as E2F targets, and mitotic spindle, and immune response-related signaling pathways, such as allograft rejection, IL2_STAT5_signaling, and inflammatory response. However, epithelial cells in primary tumors exhibited high enrichment of epithelial-mesenchymal translation (EMT), oxidative phosphorylation, and interferon alpha response. Our analysis then indicated that metastasis LN exhibited an early activated tumor microenvironment (TME) characterized by the decrease of naive T cells and an increase of cytotoxicity CD8 T cells, NK cells, FOXP3+ Treg cells compared with normal LN. By comparing the differently expressed gene of macrophages between tumor and metastatic LN, we discovered that C1QA+ MRC1low macrophages were enriched in a tumor, whereas C1QA+ MRC1high macrophages were enriched in metastatic LN. Finally, we demonstrated that cancer-associated fibroblasts (CAFs) in P-LN were associated with immune regulation, while CAFs in tumor underwent EMT. Our findings offered novel insights into the mechanisms of research, diagnosis, and therapy of CC metastasis.

AGPAT Family in Cervical Cancer: A Multi-Omics Perspective on Prognosis and Function

“…Usually not found in healthy CESC tissue, these cells increase in number in the CESC environment, encircling cancer cells and hindering the activity of effector T cells, ultimately aiding in the evasion of the immune system by the tumor 33 . Our research found that increased levels of Treg cells are linked to a worse outcome in CESC patients with high AGPAT3 expression.Conversely, in patients with low AGPAT3 expression, Treg cell levels did not signi cantly impact CESC prognosis.…”

Mitotic catastrophe heterogeneity: implications for prognosis and immunotherapy in hepatocellular carcinoma

“…CAFs can promote tumor cell mitotic proliferation via PDGFC/PDGFRA/SLUG, achieving metastasis and immune escape by regulating E2F, signal transducer and activator of transcription 5 (STAT5), etc. ( 72 , 73 ). The niche with high MC tumor cells exhibited diverse immune infiltrates.…”

Cellular heterogeneity and key subsets of tissue-resident memory T cells in cervical cancer

“…TRMs play a vital role in the immune response against tumors 9 . Previous studies have dissected the cellular heterogeneity and molecular profiles of conventional T cells within the TME of CC 25 – 27 ; however, the same in-depth characterization of TRMs has not been performed in the CC setting. Thus, in this study, we employed scRNA-seq to investigate the population characteristics of TRMs in CC.…”