Transcriptomic analysis reveals Streptococcus agalactiae activation of oncogenic pathways in cervical adenocarcinoma.

Abstract

Cervical adenocarcinoma (AC), a subtype of uterine cervical cancer (CC), poses a challenge due to its resistance to therapy and poor prognosis compared with squamous cervical carcinoma. Streptococcus agalactiae [group B Streptococcus (GBS)], a Gram-positive coccus, has been associated with cervical intraepithelial neoplasia in CC. However, the underlying mechanism interaction between GBS and CC, particularly AC, remains elusive. Leveraging The Cancer Genome Atlas public data and time-series transcriptomic data, the present study investigated the interaction between GBS and AC, revealing activation of two pivotal pathways: 'MAPK signaling pathway' and 'mTORC1 signaling'. Western blotting, reverse transcription-quantitative PCR and cell viability assays were performed to validate the activation of these pathways and their role in promoting cancer cell proliferation. Subsequently, the present study evaluated the efficacy of two anticancer drugs targeting these pathways (binimetinib and ridaforolimus) in AC cell treatment. Binimetinib demonstrated a cytostatic effect, while ridaforolimus had a modest impact on HeLa cells after 48 h of treatment, as observed in both cell viability and cytotoxicity assays. The combination of binimetinib and ridaforolimus resulted in a significantly greater cytotoxic effect compared to binimetinib or ridaforolimus monotherapy, although the synergy score indicated an additive effect. In general, the MAPK and mTORC1 signaling pathways were identified as the main pathways associated with GBS and AC cells. The combination of binimetinib and ridaforolimus could be a potential AC treatment.