This study systematically and comprehensively analyzed the characteristics of matrix metalloproteinases (MMPs) in gastric cancer (GC) and revealed the relationship between MMPs and prognoses, clinicopathological features, tumor microenvironment, gene mutations, and drug therapy response in patients with GC. Based on the mRNA expression profiles of 45 MMP-related genes in GC, we established a model that classified GC patients into three groups based on cluster analysis of the mRNA expression profiles. The 3 groups of GC patients showed significantly different prognoses as well as tumor microenvironmental characteristics. Next, we used Boruta’s algorithm and PCA method to establish an MMP scoring system and found that lower MMP scores were associated with better prognoses, lower clinical stages, better immune cell infiltration, lower degrees of immune dysfunction and rejection, and more genetic mutations. Whereas a high MMP score was the opposite. These observations were further validated with data from other datasets, showing the robustness of our MMP scoring system. Overall, MMP could be involved in the tumor microenvironment (TME), clinical features, and prognosis of GC. An in-depth study of MMP patterns can better understand the indispensable role of MMP in the development of GC and reasonably assess the survival prognosis, clinicopathological features, and drug efficacy of different patients, thus providing clinicians with a broader vision of GC progression and treatment.

IntroductionTumor immunity is a hot topic in tumor research today, and human immunity is closely related to tumor progression. T lymphocyte is an important component of human immune system, and the changes in their subsets may influence the progression of colorectal cancer (CRC) to some extent. This clinical study systematically describes and analyzes the association of CD4+ and CD8+ T-lymphocyte content and CD4+/CD8+ T-lymphocyte ratio with CRC differentiation, clinical pathological stage, Ki67 expression, T-stage, N-stage, carcinoembryonic antigen (CEA) content, nerve and vascular infiltration, and other clinical features, as well as preoperative and postoperative trends. Furthermore, a predictive model is constructed to evaluate the predictive value of T-lymphocyte subsets for CRC clinical features.MethodsStrict inclusion and exclusion criterion were formulated to screen patients, preoperative and postoperative flow cytometry and postoperative pathology reports from standard laparoscopic surgery were assessed. PASS and SPSS software, R packages were invoked to calculate and analyze.ResultsWe found that a high CD4+ T-lymphocyte content in peripheral blood and a high CD4+/CD8+ ratio were associated with better tumor differentiation, an earlier clinical pathological stage, lower Ki67 expression, shallower tumor infiltration, a smaller number of lymph node metastases, a lower CEA content, and a lower likelihood of nerve or vascular infiltration (P < 0.05). However, a high CD8+ T-lymphocyte content indicated an unpromising clinical profile. After effective surgical treatment, the CD4+ T-lymphocyte content and CD4+/CD8+ ratio increased significantly (P < 0.05), while the CD8+ T-lymphocyte content decreased significantly (P < 0.05). Further, we comprehensively compared the merits of CD4+ T-lymphocyte content, CD8+ T-lymphocyte content, and CD4+/CD8+ ratio in predicting the clinical features of CRC. We then combined the CD4+ and CD8+ T-lymphocyte content to build models and predict major clinical characteristics. We compared these models with the CD4+/CD8+ ratio to explore their advantages and disadvantages in predicting the clinical features of CRC.DiscussionOur results provide a theoretical basis for the future screening of effective markers in reflecting and predicting the progression of CRC. Changes in T lymphocyte subsets affect the progression of CRC to a certain extent, while their changes also reflect variations in the human immune system.

Purpose Colorectal cancer is a high incidence tumor, immunotherapy has become a hot topic of research in recent years, at the same time, the dysregulation of intestinal microbiota is also gaining attention because it can lead to changes in body immunity. So, we want to explore the relationship between gut microbiota and colorectal cancer. Methods We performed 16S rRNA high-throughput sequencing of tumors and paraneoplastic tissues from 30 patients, followed by at least 5 years of follow-up. Microbiome analysis, survival analysis, and then immunohistochemistry and its correlation with microbiota were performed in 19 of these patients. Results OTU13530 and OTU17086, both representing g_Sediminibacterium, showed significant differences in normalized abundance in tumor and paraneoplastic tissues (FDR < 0.05 and log2FC > 1). Both of them correlated with T-stage (p = 0.016, p = 0.024) and Her-2 expression (p = 0.034, p = 0.001). The former correlated with HIF expression (p = 0.017), and the latter with EGFR expression (p = 0.003). OTU3504, representing o_Myxococcales, had a correlation with patient survival (p = 0.015, HR = 28.5(1.9–425.0)), its abundance correlated with tumor neural invasion (p = 0.005) and vascular invasion (p = 0.005). Conclusion There is no statistical difference in the diversity and homogeneity of the microbiota between tumor and paraneoplastic tissues. But the abundance of some specific microbiota differed significantly between tumor and paraneoplastic tissues, and these microbiota correlated with patient survival, Her-2, HIF and other proteins expression, T-stage, neurovascular invasion and other clinical traits.