<p>Comprehensive Analysis of <em>CDC27</em> Related to Peritoneal Metastasis by Whole Exome Sequencing in Gastric Cancer</p>

Abstract

The peritoneum is the most common metastatic site of gastric cancer and is associated with a dismal prognosis. However, there is no reliable biomarker for predicting peritoneal metastasis (PM). Materials and Methods: Whole-exome sequencing (WES) was performed on formalinfixed, paraffin-embedded (FFPE) samples from 63 patients with stage I-III gastric cancer and circulating tumor DNA (ctDNA) samples from 10 patients with stage IV gastric cancer. Differentially expressed genes (DEGs) were identified between the PM and non-PM groups and analyzed by multiple bioinformatics analyses. Univariate and multivariate Cox regression analyses were used to identify the risk factors for PM and a risk score model was developed. Results: The number of mutant genes and the tumor mutation burden (TMB) in the PM group were higher than those in the non-PM group (p < 0.05). There was a significant positive correlation between the number of mutant genes and the TMB (R 2 = 0.9997). The risk of PM was significantly higher in the high TMB group than in the low TMB group (p = 0.045). Forty-nine DEGs were identified as associated with PM in gastric cancer. CDC27 mutations were associated with a higher risk for PM and poor survival. The CDC27 mutations were located in the Apc3 region, the TPR region, and the phosphorylation region, and new mutation sites were not included in the TCGA database. Multivariable Cox regression analysis demonstrated that pathological T stage, poor tumor differentiation, Borrmann type, and CDC27 mutations were independent predictive factors of PM. A risk score model was constructed that demonstrated good performance. Conclusion: Through WES, we identified 49 DEGs relevant to PM in gastric cancer. CDC27 mutations were independently associated with PM by statistical and bioinformatics analyses. A risk score model was built and was demonstrated to effectively discriminate gastric cancer patients with and without PM.

A paediatric dysembryoplastic neuroepithelial tumour (DNET) with deregulated stem cell markers: a case report

“…The COSMIC database includes several deregulations and mutations of this gene that are associated with embryonal tumours, suggesting a critical and primal role of this gene in driving paediatric tumorigenesis (7,25,26). Furthermore, previously identified mutations in CDC27 were shown to significantly correlate with progressive disease, low overall survival and diseasefree survival (23,27). The second gene with the most frequent TCB variants was the CTBP2 gene.…”

Whole-exome sequencing identifies prognostic mutational signatures in gastric cancer

“…AHNAK2 and CDC27 mutations have been reported to be closely linked to progression of patients with unresectable metastatic GC, and to tumorigenesis and progression by supporting epithelial-mesenchymal transition (EMT) and gaining tumor cell-like properties (17,18). CDC27 was reported to be associated with a higher risk of peritoneal metastasis and poor survival in GC (19), suggesting that patients with this mutation may benefit from immunotherapy. We found that somatic mutation of ATAD3B was related to tumor metastasis, which may provide opportunities for future study.…”

Cell‑free DNA as a liquid biopsy for early detection of gastric cancer (Review)

“…Recent advancements in NGS techniques have identified various nucleotide mutations associated with GC (Table II). The top mutated genes showing higher mutation frequency were TP53, TTN, MUC16, CDH1, KMT2C and MLH1 (31)(32)(33). In 1977, Leon et al (34) reported that numerous patients with cancer had elevated circulating cfDNA, and found that this DNA was tumor derived.…”