Search

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.

Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation.

Explore potential screening biomarkers for noninvasive diagnosis of colorectal cancer (CRC) by testing methylation of the miR-34a and miR-34b/c promoter in CRC patients’ tissue and stool samples. Methylation-specific PCR analyses were performed on sample DNAs: 82 pairs of normal/cancer samples, 82 CRC patients’ stool samples, 40 healthy volunteer stool samples, and 20 healthy volunteer blood samples were recruited. miR-34a has been found methylated in 65 of 82 (79.3 %) the CRC tissue samples, but only 36 of 82 (43.9 %) in corresponding normal samples. And when testing miR-34a in stool, 63 of 82 (76.8 %) CRC stool samples were observed methylated, and 2 of 40 (5 %) healthy samples were observed methylated. The methylation for miR-34b/c has been found in 80 of 82 (97.5 %) CRC tissue samples, 49 of 82 (59.8 %) corresponding CRC normal samples, and 74 of 79 (93.6 %) CRC stool samples. Yet we did not detect any methylation from healthy volunteers stool samples or healthy adult blood samples. Results indicated 76.8 % sensitivity and 93.6 % specificity of the miR-34a methylation test for detecting CRC using stool samples. Meanwhile, the sensitivity and specificity of miR-34b/c were 95 and 100 %, respectively. Moreover, our results revealed that abnormal DNA methylation of miR-34a was correlated with lymph metastasis (P = 0.010). Abnormal methylation of miR-34a and miR-34b/c genes might be regarded as potential biomarkers for noninvasive screening and diagnosis of colorectal cancer.

The aim of this study was to evaluate hypermethylation of the spastic paraplegia-20 promoter as a potential biomarker and prognostic factor in gastric cancer. Four human gastric cancer cell lines, 41 primary gastric cancer tissue samples and corresponding peripheral blood samples, and blood samples of 21 healthy individuals were analyzed using methylation-specific polymerase chain reaction. Additionally, the expression of Spartin, the protein product encoded by spastic paraplegia-20, was analyzed in tissues from 119 gastric cancer patients who underwent radical gastrectomy at Xi’an Jiaotong University between 2005 and 2010. Hypermethylation of the spastic paraplegia-20 promoter was observed in 26 of 41 (63.4 %) primary tumors and 1 of 35 (2.9 %) adjacent normal gastric tissues (P < 0.001). Among matched peripheral blood samples from gastric cancer patients, 48.8 % exhibited hypermethylation of the spastic paraplegia-20 promoter. In contrast, no methylation of the spastic paraplegia-20 promoter was observed in blood samples from 21 healthy individuals (P < 0.001). Additionally, demethylation by 5-aza-dC treatment led to gene reactivation in gastric cancer cells exhibiting hypermethylation of the spastic paraplegia-20 promoter. Finally, immunohistochemical staining indicated that low expression of Spartin was a prognostic factor predicting poor outcomes in gastric cancer patients (P = 0.037). These findings suggested that hypermethylation of the spastic paraplegia-20 promoter occurred frequently in gastric cancer and could represent a novel prognostic factor. Furthermore, detection of this molecular feature in the peripheral blood of gastric cancer patients suggested that evaluation of the methylation state of the spastic paraplegia-20 promoter may be used as a noninvasive screening method.