Undifferentiated-predominant mixed-type early gastric cancer is more aggressive than pure undifferentiated type: a systematic review and meta-analysis.

BACKGROUND: Studies have shown that differentiated-predominant mixed-type early gastric cancer (EGC) is more aggressive than pure differentiated-type EGC. However, the biological behaviour of undifferentiated-predominant mixed-type (MU) EGC and pure undifferentiated-type (PU) EGC are controversial. This study was conducted to compare the biological behaviour of MU EGC and PU EGC. METHODS: A systematic review and meta-analysis of observational studies was conducted using literature published through PubMed and Embase from inception to 9 November 2021. Inclusion criteria were: (1) a direct or indirect comparison of MU and PU; (2) patients with EGC; (3) a specified outcome of lymph node metastasis (LNM), lymphovascular invasion, submucosal invasion and/or ulcer findings; and (4) the primary lesion was obtained. The literature search, data extraction and quality assessment were performed by two independent reviewers. The meta-analysis was conducted with a random-effect model using the Mantel-Haenszel method. RESULTS: Twelve publications with 5644 patients were included. Patients with MU EGC had significantly higher risk of LNM (OR 2.28; 95% CI 1.72 to 3.03) and submucosal invasion (OR 2.19; 95% CI 1.90 to 2.52) compared with patients with PU EGC. No difference was found between patients with MU and PU EGC with respect to lymphovascular invasion risk (OR 1.81; 95% CI 0.84 to 3.87). After stratifying the data according to depth of tumour invasion, a significantly higher risk for LNM was associated with intramucosal MU EGC (OR 2.56; 95% CI 1.66 to 3.95) and submucosal MU EGC (OR 2.63; 95% CI 2.06 to 3.06). Submucosal MU EGC also had a significantly higher risk of lymphovascular invasion (OR 2.40; 95% CI 1.79 to 3.21) compared with submucosal PU EGC. DISCUSSION: Patients with MU EGC had an increased risk of submucosal invasion and LNM compared with patients with PU EGC . MU patients with submucosal EGC also had an increased lymphovascular invasion risk compared with PU patients. Therefore, attention should be focused on the clinical management of patients with MU EGC.

Identification of a novel m6A-related lncRNA pair signature for predicting the prognosis of gastric cancer patients.

BACKGROUND: Accumulating studies have demonstrated that lncRNAs play vital roles in the prognosis of gastric cancer (GC); however, the prognostic value of N6-methyladenosine-related lncRNAs has not been fully reported in GC. This study aimed to construct and validate an m6A-related lncRNA pair signature (m6A-LPS) for predicting the prognosis of GC patients. METHODS: GC cohort primary data were downloaded from The Cancer Genome Atlas. We analysed the coexpression of m6A regulators and lncRNAs to identify m6A-related lncRNAs. Based on cyclical single pairing along with a 0-or-1 matrix and least absolute shrinkage and selection operator-penalized regression analyses, we constructed a novel prognostic signature of m6A-related lncRNA pairs with no dependence upon specific lncRNA expression levels. All patients were divided into high-risk and low-risk group based on the median risk score. The predictive reliability was evaluated in the testing dataset and whole dataset with receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis was used to identify potential pathways. RESULTS: Fourteen m6A-related lncRNA pairs consisting of 25 unique lncRNAs were used to construct the m6A-LPS. Kaplan-Meier analysis showed that the high-risk group had poor prognosis. The area under the curve for 5-year overall survival was 0.906, 0.827, and 0.882 in the training dataset, testing dataset, and whole dataset, respectively, meaning that the m6A-LPS was highly accurate in predicting GC patient prognosis. The m6A-LPS served as an independent prognostic factor for GC patients after adjusting for other clinical factors (p < 0.05). The m6A-LPS had more accuracy and a higher ROC value than other prognostic models for GC. Functional analysis revealed that high-risk group samples mainly showed enrichment of extracellular matrix receptor interactions and focal adhesion. Moreover, N-cadherin and vimentin, known biomarkers of epithelial-mesenchymal transition, were highly expressed in high-risk group samples. The immune infiltration analysis showed that resting dendritic cells, monocytes, and resting memory CD4 T cells were significantly positively related to the risk score. Thus, m6A-LPS reflected the infiltration of several types of immune cells. CONCLUSIONS: The signature established by pairing m6A-related lncRNAs regardless of expression levels showed high and independent clinical prediction value in GC patients.