Objective To investigate relationship between hypoxia microenvironment and occurrence and development of hepatocellular carcinoma (HCC). Method The relevant literatures on researches of the relationship between the hypoxic microenvironment and the HCC were review and analyzed. Results The hypoxia microenvironment played an important role in inducing the drug resistance and angiogenesis of the HCC cells, and it was an important factor of affecting the ability of tumor metabolism, invasion, and migration. The hypoxia microenvironment could up-regulate the expression of hypoxia-inducible factors (HIFs) and promote its transcriptional activity, promote the expression of the vascular endothelial growth factor gene, and regulate the neovascularization in the tumor. Among them, the HIF-1α played a major role in regulating the angiogenesis, immune escape, tumor invasion and metastasis-related gene expression, participating in the glycolysis, regulating lysyl oxidase 2 and thus regulated epithelial-mesenchymal transition, then promoted the invasion and metastasis of the HCC; HIF-2α was a key regulator of the malignant phenotype involving in the cell proliferation, angiogenesis, apoptosis, metabolism, metastasis, and resistance to chemotherapy. The hypoxia microenvironment posed some difficulties for the treatment of HCC, but it was also a potential therapeutic breakthrough. Conclusion Hypoxia microenvironment can promote invasion and metastasis of HCC through various mechanisms, which provides new targets and strategies for clinical treatment of HCC.
ObjectiveTo understand the single-cell RNA sequencing (scRNA-seq) and its research progress in the tumor microenvironment (TME) of breast cancer, in order to provide new ideas and directions for the research and treatment of breast cancer. MethodThe development of scRNA-seq technology and its related research literature in breast cancer TME at home and abroad in recent years was reviewed. ResultsThe scRNA-seq was a quantum technology in high-throughput sequencing of mRNA at the cellular level, and had become a powerful tool for studying cellular heterogeneity when tissue samples were fewer. While capturing rare cell types, it was expected to accurately describe the complex structure of the TME of breast cancer. ConclusionsAfter decades of development, scRNA-seq has been widely used in tumor research. Breast cancer is a malignant tumor with high heterogeneity. The application of scRNA-seq in breast cancer research can better understand its tumor heterogeneity and TME, and then promote development of personalized diagnosis and treatment.
ObjectiveTo analyze the correlation between the molecular biological information of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) and its clinical prognosis, and to explore the spatial features and molecular mechanisms of interactions between cells in the tumor microenvironment (TME) of SMARCA4-dNSCLC. MethodsUsing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), this study conducted functional enrichment analysis on differentially expressed genes (DEGs) in SMARCA4-dNSCLC and depicted its genomic variation landscape. Through weighted gene co-expression network analysis (WGCNA) and a combination of 10 different machine learning algorithms, patients in the training group were divided into a low-risk group and a high-risk group based on a median risk score (RiskScore). A corresponding prognostic prediction model was established, and on this basis, a nomogram was constructed to predict the 1, 3, and 5-year survival rates of patients. K-M survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model. External datasets from GEO further validated the prognostic value of the prediction model. In addition, we also evaluated the immunological characteristics of the TME of the prognostic model. Finally, using single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST), we explored the spatial features of interactions between cells in the TME of SMARCA4-dNSCLC, intercellular communication, and molecular mechanisms. ResultsA total of 56 patients were included in the training group, including 38 males and 18 females, with a median age of 62 (56-70) years. There were 28 patients in both the low-risk and high-risk groups. A total of 474 patients were included in the training group, including 265 males and 209 females, with a median age of 65 (58-70) years. A risk score model composed of 8 prognostic feature genes (ELANE, FSIP2, GFI1B, GPR37, KRT81, RHOV, RP1, SPIC) was established. Compared with patients in the low-risk group, those in the high-risk group showed a more unfavorable prognostic outcome. Immunological feature analysis revealed differences in the infiltration of various immune cells between the low-risk and high-risk groups. ScRNA-seq and ST analyses found that interactions between cells were mainly through macrophage migration inhibitory factor (MIF) signaling pathways (MIF-CD74+CXCR4 and MIF-CD74+CD44) via ligand-receptor pairs, while also describing the niche interactions of the MIF signaling pathway in tissue regions. ConclusionThe 8-gene prognostic model constructed in this study has certain predictive accuracy in predicting the survival of SMARCA4-dNSCLC. Combining the ScRNA-seq and ST analyses, cell-to-cell crosstalk and spatial niche interaction may occur between cells in the TME via the MIF signaling pathway (MIF-CD74+CXCR4 and MIF-CD74+CD44).
Objective To summarize research status and mechanism about effects of carcinoma-associated fibroblasts (CAFs) on breast cancer stem cells. Method Relevant literatures about the relationship between the CAFs and breast cancer stem cells were collected and reviewed. Results CAFs were the majority type of the breast cancer stromal cells. The cancer stromal cell was also the important part of the tumor microenvironment, which could promote the proliferation, adhesion, invasion, and metastasis of the breast cancer. A subpopulation of cancer stem cells with the potentials of self-renewal and multi-directional differentiation in the breast cancer tissues might cause the tumor development. There was a phenotypic heterogeneity in the beast cancer stem cells, it was related to the tumor recurrence and therapy resistance. The CAFs could promote the formation of breast cancer stem cells through the epithelial mesenchymal transition and promote the transformation of tumor stem cell phenotype. More research needed to be done to prove these processes. Conclusion CAFs play an important role in formation of breast cancer stem cells and transformation of tumor stem cell phenotype, which might provide a new idea about treating breast cancer.
ObjectiveTo introduce the research status of the immunoregulation function of cancer-associated fibroblasts (CAFs) in tumor microenvironment.MethodThe literatures in recent years on the studies of role of CAFs in the regulation of immune response in the tumor microenvironment were collected and summarized.ResultsThe CAFs played a critical role as the components of the tumor microenvironment. The CAFs could product various growth factors and cytokines that were contributed to the immunoregulation including the polarization of the immune cells and the regulation of the function of immune cells in the tumor microenvironment and eventually resulted in the carcinogenesis, tumor progression, invasion, metastasis and therapy resistance.ConclusionCAFs play a significant role in the immunoregulation in tumor microenvironment, but as a potential target for breast cancer, more studies are still needed to discover the specific markers, heterogeneity, and key signaling pathways.
ObjectiveTo review the role of intestinal flora on the tumor microenvironment and the effect of both on the development of hepatocellular carcinoma (HCC), with a view to providing new ideas on the causes of HCC development and progression. MethodRelevant articles in the direction of intestinal flora and tumor microenvironment and HCC as well as the relationship between intestinal flora and tumor microenvironment in recent years were searched and summarized. ResultsThe tumor microenvironment played an important role in the occurrence, development and postoperative recurrence of HCC. The intestinal flora, as one of the important regulators of tumor microenvironment, could induce HCC by affecting the tumor microenvironment in addition to interacting with the liver through the gut-liver axis. ConclusionIntestinal flora can influence to HCC by regulating the tumor microenvironment, and its specific mechanism of action still needs to be further investigated, which can be a new direction for HCC research.
ObjectiveTo summarize the research progress of hepatocellular carcinoma (HCC) based on tumor microenvironment immunophenotyping.MethodThe related literatures of basic and clinical studies on HCC immunophenotyping in the recent years were reviewed.ResultsHCC could be divided into different immunophenotypes based on tumor microenvironment, and it showed different immune molecular characteristics, immune cell infiltration characteristics, and anti-tumor ability. At the same time, the HCC immunophenotype was significantly associated with patients’ survival and had been proved to be able to better evaluate the prognosis of HCC patients. According to the relevant molecular characteristics in the HCC immune microenvironment, it could provide guidance for the drug regimen of immunotherapy.ConclusionHCC immunophenotyping is still in the early stage of research, and its clinical application value has been preliminarily shown for the evaluation of patients’ prognosis and immunotherapy decision-making, which is a new idea of individualized treatment of HCC in the future.
ObjectiveTo summarize the relationship between integrins, tumor metabolism, and tumor cells with pancreatic stellate cells in the tumor microenvironment, in order to provide targets and ideas for the treatment of pancreatic ductal adenocarcinoma.MethodTo review the literatures on pancreatic stellate cells, integrins, and amino acid metabolism as therapeutic targets for pancreatic ductal adenocarcinoma in the domestic and overseas.ResultsThe drug research for pancreatic ductal adenocarcinoma was currently under vigorous development, but remain in the animal and clinical test stage. As a new therapeutic protein, ProAgio could inhibit the expression of integrin αvβ3, activation and secretion of pancreatic stellate cells, and alanine metabolism in the microenvironment of pancreatic ductal adenocarcinoma, so as to achieve the dual effects of anti-fibrosis and anti-tumor.ConclusionsThe roles of activated pancreatic stellate cells, ProAgio, integrin αvβ3, and alanine metabolism in pancreatic ductal adenocarcinoma have been partially elucidated, but the specific mechanism still needs further investigation and may become a completely new therapeutic target someday.
ObjectiveTo summarize the relationship between exosomes and the occurrence and development of gastrointestinal cancer.MethodsThrough online database, we collected the literatures about the relationship between exosomes and the development of gastrointestinal cancer at home and abroad, and then made an review.ResultsExosomes secreted by gastrointestinal cancer cells were related to tumorigenesis, tumor cell survival, chemoresistance, and early metastasis. Exosomes could play the role of information transmission, and regulation of cell physiology and pathological process in the development of gastrointestinal cancer through a variety of intercellular binding ways, and affectted the occurrence and development of gastrointestinal cancer via epigenetic regulation and tumor related signal transduction mechanism. They had been proved to be biomarkers, targets, and drug carriers for the treatment of gastrointestinalcancer.ConclusionIt is a new way to explore the molecular mechanism of exosomes in the development of gastrointestinal cancer.
Objective To introduce the research status of the immunomodulatory role of various immune cells and stromal cells in the tumor microenvironment in the progression of hepatocellular carcinoma. Method The related basic and clinical research literatures on the correlation between various immune cells and stromal cells in the tumor microenvironment and the occurrence, development and prognosis of hepatocellular carcinoma were reviewed and summarized. Results Immune cells and stromal cells in the tumor microenvironment have obvious complexity and diversity. Inhibitory immune cells in various immunosuppressive environments and stimulating immune cells that exert anti-tumor effects jointly promote or inhibit the occurrence and progression of hepatocellular carcinoma. Conclusions The exact role of various immune cells in the tumor microenvironment in hepatocellular carcinoma remains to be further studied. With the continuous accumulation of relevant research results, more patients with hepatocellular carcinoma will benefit from immunotherapy.