ABSTRACT
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.
ABSTRACT
Introduction: Tumor 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. Methods: Strict 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. Results: We 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. Discussion: Our 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.
