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The role of squamous cell carcinoma antigen (SCC Ag) in outcome prediction after concurrent chemoradiotherapy and treatment decisions for patients with cervical cancer.

ABSTRACT: At present, the standard treatment approach for locally advanced cervical cancer is concurrent chemoradiotherapy (CCRT). An elevated pretreatment squamous cell carcinoma antigen (SCC Ag) level is associated with extensive tumors and poor survival for patients with cervical cancer treated with definitive CCRT. SCC Ag levels can be used to help physicians make decisions regarding surgery, avoiding the complications of double treatment modalities. Elevated SCC Ag is associated with radiotherapy resistance, and the rate of SCC Ag reduction during CCRT can predict tumor response after treatment. Moreover, the failure of SCC Ag levels to normalize posttreatment can predict tumor relapse, with a specificity higher than 70%, and adjuvant therapies should be considered for these patients. SCC Ag also plays an important role in the early detection of tumor relapse in patients with cervical cancer during follow-up after CCRT, with high sensitivity and good cost-effectiveness.

SUBMITTER: Fu J

PROVIDER: S-EPMC6694518 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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The role of squamous cell carcinoma antigen (SCC Ag) in outcome prediction after concurrent chemoradiotherapy and treatment decisions for patients with cervical cancer.

Fu Jingxuan J Wang Weiping W Wang Yidan Y Liu Chengeng C Wang Peichang P

Radiation oncology (London, England) 20190815 1

At present, the standard treatment approach for locally advanced cervical cancer is concurrent chemoradiotherapy (CCRT). An elevated pretreatment squamous cell carcinoma antigen (SCC Ag) level is associated with extensive tumors and poor survival for patients with cervical cancer treated with definitive CCRT. SCC Ag levels can be used to help physicians make decisions regarding surgery, avoiding the complications of double treatment modalities. Elevated SCC Ag is associated with radiotherapy res ...[more]

PMID: 31416463

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Project description:Background:Cervical squamous cell carcinoma (CSCC) is the main pathological type of cervical cancer, accounting for 80%-85% of cervical cancer. Owing to concurrent chemoradiotherapy (CCRT) resistance in a subset of CSCC patients, the treatment response is often unsatisfactory. Identifying predictors and therapeutic targets related to cisplatin-based CCRT resistance in CSCC is critical. Methods:We reanalyzed GSE56363, an mRNA dataset from the GEO database with 21 patients with locally advanced CSCC, to identify differentially expressed genes (DEGs) related to CCRT resistance. The hub genes were screened from the protein-protein interaction network of DEGs using cytoHubba plug-in of Cytoscape software. Transcriptome sequencing technology was used to compare differential expression between SiHa cells overexpressing BRCA1 compared with control SiHa cells. Functional annotation for DEGs and gene set enrichment analysis (GSEA) was performed to identify DEG-enriched relative signaling pathways to examine the molecular mechanisms of BRCA1 in CCRT resistance of CSCC. qPCR was used to verify the expression of key genes in SiHa/DDP cells. Results:A total of 609 DEGs including 223 upregulated DEGs and 386 downregulated DEGs were identified between the complete response to CCRT (CR) and noncomplete response to CCRT (NCR) CSCC patients based on the GSE56363 dataset. Ten hub genes with the highest degrees were identified via the plug-in CytoHubba in Cytoscape: BRCA1, CDCA8, ASPM, CDC45, RAD51, HMMR, CENPF, EXO1, DTL, and ZWINT genes, and BRCA1 ranked first. Through transcriptome sequencing analysis based on GSE141558, 1344 DEGs were identified in BRCA1-overexpressing SiHa cells, including 824 upregulated DEGs and 520 downregulated DEGs. GSEA results showed that CCRT-resistance related signaling pathways, such as the JAK/STAT signaling pathway and the WNT signaling pathway, were differentially enriched in BRCA1-expressing SiHa cells. STAT1, STAT2, and CCND1 were screened as the differentially expressed target genes of BRCA1 and may correlate with resistance of CSCC. qPCR results showed that only STAT1 was significantly increased in SiHa cells with GV230-BRCA1 plasmid transfection. Conclusion:BRCA1 overexpression in SiHa cells may upregulate STAT1 to activate the JAK/STAT signaling pathway, suggesting a mechanism for enhanced CCRT resistance.

Project description:BACKGROUND:To study the kinetic profile and clinicopathological implications of squamous cell carcinoma antigen (SCC-Ag) in cervical cancer patients who underwent surgery by a self-developed SCC-Ag single molecule assay (Simoa) prototype immunoassay. METHODS:Participants were prospectively enrolled between 04/2016 and 06/2017. Consecutive serum samples were collected at five points: day 0 (the day before surgery), postoperative day 4, weeks 2-4, months 2-4 and months 5-7. In total, 92 patients and 352 samples were included. The kinetic change in SCC-Ag levels and their associations with clinicopathological characteristics were studied. RESULTS:Simoa SCC-Ag was validated by comparison with the Architect assay. SCC-Ag levels measured by the Simoa assay were highly correlated with the Architect assay's levels (Pearson's correlation coefficient?=?0.979, Passing-Bablok regression slope 0.894 (0.847 to 0.949), intercept -?0.009 (-?0.047 to 0.027)). The median values for each time-point detected by the Simoa assay were 2.49, 0.66, 0.61, 0.72, and 0.71?ng/mL, respectively. The SCC-Ag levels decreased dramatically after surgery and then stabilized and fluctuated to some extent within 6?months. Patients with certain risk factors had significantly higher SCC-Ag values than their negative counterparts before surgery and at earlier time points after surgery, while no difference existed at the end of observation. Furthermore, although patients with positive lymph nodes had sustained higher SCC-Ag levels compared to those with negative lymph nodes, similar kinetic patterns of SCC-Ag levels were observed after surgery. Patients who received postoperative treatment had significantly higher SCC-Ag values than those with surgery only at diagnosis, while no difference existed after treatment. CONCLUSIONS:The Simoa SCC-Ag prototype was established for clinical settings. The SCC-Ag levels were higher in patients with risk factors, whereas the kinetic trend of SCC-Ag might be mainly affected by postoperative adjuvant therapy. These data indicate that the SCC-Ag level might be a good predictor for the status of cervical cancer, including disease aggressiveness and treatment response.

Dataset Information

The role of squamous cell carcinoma antigen (SCC Ag) in outcome prediction after concurrent chemoradiotherapy and treatment decisions for patients with cervical cancer.

Publications

The role of squamous cell carcinoma antigen (SCC Ag) in outcome prediction after concurrent chemoradiotherapy and treatment decisions for patients with cervical cancer.

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