ObjectiveTo summarizes the mechanisms of carcinogenesis of colorectal cells, the occurrence and development of cancer cells, and their interactions with the tumor niche of colorectal cancer (CRC) from the perspective of the tumor niche, exploring new ideas for the prevention, diagnosis, and treatment of CRC. MethodThe relevant literature at home and abroad in recent years on the researches of mechanism of the occurrence and development of CRC and its relation with the tumor niche of CRC was searched and reviewed. ResultsThe theory of tumor ecology indicates that the human normal body can be regarded as a relatively closed and perfect ecosystem. Each normal tissue and organ within the body represent a niche in this ecosystem, which interact, affect, and symbiotically coexist with each other, forming a dynamic ecological balance. Tumor cells, being a “new species” distinct from normal tissue cells, “invade” the ecological system of the normal body under specific conditions and interact with the surrounding microenvironment, which is defined as the tumor niche. Analysis of current literature retrieved from the perspective of the tumor niche suggested that, although genetic factors are involved in the carcinogenesis of colorectal cells, the majority of such carcinogenesis stems from the continuous stimulation of the colorectal niche. Current research primarily focuses on the conclusion that the carcinogenesis of colorectal cells is associated with factors such as chronic inflammatory response, intestinal microorganisms, oxidative stress, and pyroptosis. After carcinogenesis and the eventual formation of CRC, the growth of cancer cells and tissues first requires breaching the defense of the immune system in the colorectal niche. Immune cells in the immune system play a crucial role in the tumor niche during the occurrence and development of CRC. ConclusionsThe proposal of the tumor niche concept enables researchers, when studying the mechanisms of tumor occurrence and development, to no longer merely focus on the tumor and its microenvironment. Instead, the tumor as a part of the body’s ecosystem was studied. Components of the tumor niche, such as chronic inflammatory responses, intestinal microorganisms, oxidative stress, pyroptosis, and immune system, have a significant impact on the mechanisms of carcinogenesis of most colorectal cells, as well as the occurrence and development of cancer cells. These factors influence the progression of CRC in various aspects.
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 review cancer associated fibroblasts(CAFs) and its role in the evolution of gastrointestinal neoplasms. MethodDomestic and international publications in relation to CAFs and its role in the evolution of gastrointestinal neoplasms were collected and reviewed. ResultsIn the gastrointestinal cancers, as the largest number and the most important stromal cells of the tumor microenvironment, CAFs induce the homeostasis of cell microenviron-ment out of balance, promote the remodeling of the tumor metabolism and extracellular matrix(ECM), and thus impulse the generation, proliferation, invasion and metastasis of the tumor by secreting different kinds of cytokines. ConclusionsThe key role CAFs playing in the tumor generation and evolution makes themselves and the multiple relatively specific molecules they secrete a new target for prognosis and targeted therapy, and this gives us a new idea for the combined treatment of gastrointestinal tumor or any other tumors.
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.
In the tumor microenvironment, tumor-associated macrophage, as polarized macrophages M2 phenotype, can promote tumor progression and affect the prognosis of cancer. Significant attention has been drawn towards tumor-associated macrophage in recent years. In this review, we describe the polarization state of macrophages determined by tumor microenvironment and the recruitment of tumor-associated macrophage. We also pay special attention to the interaction between tumor-associated macrophages and tumors, discuss and summarize various targeted therapy strategies for tumor-associated macrophages, aiming to provide a reference for the future development of these novel and effective anti-cancer treatments.
Uveal melanoma (UM) is an aggressive and lethal tumor in the eye. The complexity and heterogeneity of UM and its microenvironment leads to a lack of strategies for early prevention and treatment of metastases. Single-cell sequencing technologies provide critical insights into deciphering the complexity of intratumor heterogeneity and the microenvironment by enabling genomic, transcriptomic, and epigenetic analysis at the single-cell level. With the help of bioinformatics analysis combined with artificial intelligence algorithms, molecular indicator systems related to prognosis as well as therapeutic targets can be found, which can provide a basis for guiding the selection of clinical treatment plans. However, the single-cell sequencing technology also has certain limitations, such as high sample requirements, expensive and time-consuming sequencing. It is believed that with the improvement of science and technology and the update of analytical methods, these shortcomings can be gradually solved, and this rare tumor will eventually be overcome in the future, and the goal of long-term survival of UM patients will be achieved.
Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
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.
ObjectiveTo construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. ResultsA total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.
ObjectiveTo detect the expression of programmed cell death ligand 1 (PD-L1) in papillary thyroid carcinoma (PTC) and PTC with coexistent Hashimoto’s thyroiditis (HT) tissues, and to explore its clinical significance of its expression.MethodsThe PTC patients who underwent thyroidectomy at the Thyroid Surgery Department of the Affiliated Hospital of Guizhou Medical University from March 2017 to May 2019 were retrospectively collected. Immunohistochemical staining was used to detect the expression of PD-L1 in the PTC tissues, PD-L1 staining positive cells ≥20% was judged as positive expression, <20% was judged as negative expression. The relationship between PD-L1 positive expression rate and clinicopathologic characteristics of patients with PTC were analyzed, and the correlation between the presence of HT in PTC tissues and PD-L1 positive expression was studied.ResultsA total of 138 patients with PTC were included in this study, including 104 patients with PTC alone and 34 PTC patients with coexistent HT. The positive rate of PD-L1 expression in the 138 cases of PTC tissues was 35.5% (49/138), among which was 43.3% (45/104) in the pure PTC tissues, and 11.8% (4/34) in the PTC tissues with HT, the latter was significantly lower than the former (P=0.001). The results of univariate analysis showed that the positive rate of PD-L1 expression was related to the tumor size, the presence or absence of extraglandular invasion and HT in PTC patients (P<0.05), and the results of Spearman correlation analysis showed that the positive rate of PD-L1 expression was positively correlated with tumor size (rs=0.173, P=0.041) and extraglandular invasion (rs=0.197, P=0.021), and negatively correlated with whether TH was merged (rs=–0.284, P=0.001). The multivariate analysis results showed that the positive rate of PD-L1 expression was closely related to whether PTC with coexistent HT [OR=5.720, 95%CI (1.879, 17.411), P=0.002], and it was not found to be related to tumor size and presence of extraglandular invasion (P>0.05).ConclusionsPositive rate of PD-L1 expression has a certain relationship with tumor size and presence or absence of extraglandular invasion, and which in PTC patients with or without HT is significantly different, that is, positive rate of PD-L1 expression in PTC with HT is lower suggests that coexistent HT might be an inhibitory factor in occurrence of PTC, and immune microenvironment-related factors of PTC might be involved in occurrence and development of thyroid cancer.