Genetic analysis of cervical cancer with lymph node metastasis

To find out the differences in gene characteristics between cervical cancer patients with and without lymph node metastasis, and to provide reference for therapy.

From January 2018 to June 2022, recurrent cervical cancer patients 39 cases with lymph node metastasis and 73 cases without lymph node metastasis underwent testing of 1,021 cancer-related genes by next-generation sequencing. Maftools software was used to analyze somatic single nucleotide/insertion-deletion variation mutation, co-occurring mutation, cosmic mutation characteristics, oncogenic signaling pathways.

EP300 and FBXW7 were significantly enriched in lymph node-positive patients. Lymph node-positive patients with EP300 or FBXW7 mutations had lower overall survival (OS) after recurrence. Both lymph node-positive and -negative patients had plenty of co-occurring mutations but few mutually exclusive mutations. Lymph node-positive co-occurring mutation number ≥6 had lower OS, while lymph node-negative co-occurring mutation number ≥3 had lower OS after recurrence. The etiology of SBS3 was defects in DNA double strand break repair by homologous recombination, which exclusively exist in lymph node-positive patients. There was no difference in median tumor mutation burden (TMB) between positive and negative lymph nodes, but TMB was significantly associated with PIK3CA mutation.

The somatic SNV/Indels of EP300 and FBXW7, SBS3 homologous recombination-mediated DNA repair defect were enriched in lymph node-positive patients. For lymph node-positive patients, EP300 or FBXW7 mutations predicted poor prognosis. No matter lymph node-positive or negative, more co-occurring mutation number predicted poor prognosis. PIK3CA mutation may account for the higher TMB and help identify patients who benefit from immunotherapy.