期刊
CANCER RESEARCH AND TREATMENT
卷 54, 期 4, 页码 1209-1218出版社
KOREAN CANCER ASSOCIATION
DOI: 10.4143/crt.2021.963
关键词
Uterine cervical neoplasms; Neoadjuvant therapy; Pathologic response; Disease-free survival; DNA damage repair
类别
资金
- Natural Science Foundation of China [NSFC81872475, NSFC81372413, NSFC81972683]
- National key Research and Development Program [2018YFC1313200]
- Shandong Natural Science Foundation [ZR2019LZL018]
- Shandong Key Research and Development Plan [2017CXGC1209, 2017GSF18164]
- Outstanding Youth Natural Science Foundation of Shandong Province [JQ201423]
- Jinan Clinical Medicine Science and Technology Innovation Plan [201704095]
- National Key Research and Development Program of China [2016YFC0904700]
This study analyzed the genetic alterations in locally advanced cervical cancer patients who received neoadjuvant therapy and found differences in gene mutation frequency between Asian and Caucasian cohorts. High tumor mutation burden, TP53 polymorphism, and KEAP1 mutations were associated with poor treatment response, while KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse.
Purpose Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients' tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.
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