ObjectiveThis study aimed to develop prognostic prediction models for patients with Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG) who received neoadjuvant therapy (neoadjuvant chemoradiotherapy or neoadjuvant chemotherapy) and radical surgery. A baseline nomogram and a post-operative nomogram were constructed before neoadjuvant therapy and after surgery. The predictive performance of the constructed nomograms was internally validated and compared to the TNM staging system.Materials and MethodsA total of 245 patients diagnosed with Siewert type II/III AEG and treated with neoadjuvant therapy followed by radical surgery at The Fourth Hospital of Hebei Medical University between January 2011 and December 2017 were enrolled. The variables before neoadjuvant therapy were defined as baseline factors, while the variables of baseline factors along with the variables of treatment and postoperative pathology were defined as post-operative factors. To construct the corresponding nomograms, independent predictors of baseline and post-operative factors were identified. The C-index and a time-dependent receiver operating characteristic curve were used to evaluate the model’s discrimination ability. The calibration ability of the model was determined by comparing the probability of predicted free-recurrence to the actual free-recurrence. Decision curve analysis (DCA) was used to determine the clinical usefulness of the nomogram.ResultsAmong the baseline factors, age, cT stage, cN stage, Borrmann type, and staging laparoscopy were independent prognostic predictors. In contrast, among the post-operative factors, age, cN stage, staging laparoscopy, ypT stage, clinical response, number of positive lymph nodes, number of negative lymph nodes, laurén classification, and lymphatic, or perineural invasion (VELPI) were independent prognostic predictors. The two nomograms were constructed using the independent predictors of prognosis. The C-indexes for the baseline and post-operative nomograms were 0.690 (95% CI, 0.644-0.736) and 0.817 (95% CI, 0.782-0.853), respectively. The AUCs of the baseline nomogram at 3 and 5 years were both greater than cTNM (73.1 vs 58.8, 76.1 vs 55.7). Similarly, the AUCs of the post-operative nomogram were both greater than ypTNM (85.2 vs 69.1, 88.2 vs 71.3) at 3 and 5 years. The calibration curves indicated that both models had a high degree of calibration ability. By comparing the DCA at 3 and 5 years, we determined that the two nomograms constructed had better clinical utility than the TNM staging system.ConclusionsThe constructed nomograms have a more accurate predictive ability than the eighth edition TNM staging system, which can be useful for treatment selection and follow-up monitoring of patients.

The aim of the present study was to detect mutations in the coding genes of mitochondrial DNA (mtDNA) in three esophageal cancer cell lines and in tumor tissues obtained from 30 patients with esophageal cancer, to investigate the relationship between protein‑ and RNA‑coding gene mutations and esophageal cancer. mtDNA was extracted and the coding genes were sequenced and analyzed by comparing the sequencing results with the complete mitochondrial genome of Homo sapiens. The results revealed 39 mutations in the three esophageal cancer cell lines; the genes with the highest mutation frequencies included mitochondrially encoded cytochrome B (MT‑CYTB), NADH dehydrogenase 5 (MT‑ND5) and MT‑ND4 gene. A total of 216 mutations were identified in the 30 esophageal cancer tissues, including 182 protein‑coding mutations, of which MT‑CYTB and MT‑ND5 genes exhibited higher mutation frequencies. The results of the present study indicated that mutations in the coding genes of mtDNA in esophageal cancer cells may be related to the occurrence of esophageal cancer.

The present study aimed to detect the mutation characteristics of mitochondrial DNA (mtDNA) in Eca109 of Ec9706 cells, and to investigate their association with the nuclear genome (nDNA), thus providing a basis for gene targeting therapies for esophageal squamous cell carcinoma (ESCC). In vitro-cultured Ec9706 and Eca109 cells were analyzed the changes of single-nucleotide polymorphisms (SNPs), insertions/deletions (INDELs), copy number variation, and structure variation (SV) of their genome by high-throughput sequencing. The loci with SV on chromosome 1–12 of the two ESCC cell lines were ≥5% of the mtDNA, but SV on chromosome 13–22, X and Y was ≤3%; >40% of loci exhibited gain or loss; intergenic loci with INDEL changes and SNP features accounted for the majority of mutations. The affected genes encoded proteins including nDNA-encoding intra-mitochondrial-transporting proteins, ATP energy generation-associated proteins and mitochondrial electron respiratory chain proteins, and these proteins were all nucleus-encoded mitochondrial proteins. The transcription, duplication, and translation of the abnormally expressed mtDNA in Ec9706 and Eca109 cells were closely associated with disorders of nuclear DNA products.