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.
ObjectiveTo investigate the effect of Wnt5a derived from tumor-associated fibroblasts （CAFs） on the migration and invasion of gastric cancer cells. MethodsThe differentially expressed genes Wnt5a between CAFs and normal gastric fibroblasts (NGFs) in gastric cancer tissues and their corresponding normal gastric tissues using the GEO database GSE194261 dataset were screened. Immunohistochemical method was used to detect the expression of Wnt5a protein in tissue samples of clinical gastric cancer patients, and the relationship between Wnt5a protein expression and clinicopathological features of gastric cancer was analyzed. CAFs and NGFs were extracted from fresh surgical specimens of gastric cancer patients, and the expression of Wnt5a in CAFs was detected by real-time fluorescence quantitative-polymerase chain reaction and Western blot experiment. Transwell invasion and migration experiment was used to observe the effects of CAFs, inhibition of Wnt5a expression in CAFs and different concentrations of recombinant Wnt5a protein on the migration and invasion ability of gastric cancer MGC-803 and MKN-28 cell lines in vitro. ResultsThrough the screening of GEO database GSE194261 data set, it was found that Wnt5a was more expressed in CAFs than NGFs (P<0.05). Immunohistochemical results showed that the expression of Wnt5a protein in gastric cancer tissues was significantly stronger than that in normal gastric tissues (P<0.05), and the expression of Wnt5a protein was related to T stage of tumor (χ2=5.035, P<0.05), but not related to gender, age, degree of tumor differentiation, lymph node metastasis, vascular invasion and nerve invasion (P>0.05). Inhibiting Wnt5a derived from CAFs could inhibit the invasion and migration of gastric cancer cells. By stimulating gastric cancer cells with different concentrations of human recombinant Wnt5a protein, it was found that when the concentration of human recombinant Wnt5a protein was greater than 100 ng/mL, the invasion and migration abilities of MGC-803 and MKN-28 gastric cancer cells were significantly increased (P<0.05). ConclusionWnt5a is highly expressed in CAFs derived from the interstitial tissue of gastric cancer, which is related to the invasion depth of gastric cancer and can promote the invasion and migration of gastric cancer cells.
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 summarize the research results of metabolites of breast cancer based on metabonomics technology, and systematically reviews them in order to provide a new direction for the research of metabolism of breast cancer.MethodBy searching the relevant literatures in recent years, the application of metabonomics in identifying high-risk breast cancer population, monitoring the progress of tumor and evaluating the response of radiotherapy and chemotherapy were analyzed and summarized.ResultsWith the development of high-resolution, high-sensitivity and high-throughput bioanalysis platform technology, metabolomics had been widely used in breast cancer research field by virtue of its unique perspective and technical advantages to more accurately, systematically and dynamically monitor the changes of host metabolites.ConclusionMetabolomics technology provides a new research direction for primary prevention, early screening and diagnosis of breast cancer and optimal treatment strategy selection.
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 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 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.
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 analyze the immune landscape and gene expression patterns associated with CD8+T-cell subtypes in papillary thyroid carcinoma by using bioinformatics, construct a prognostic model, and performe analyses of immune infiltration characteristics. MethodsWe integrated single-cell RNA sequencing and Bulk transcriptomic data, using differential expression analysis, cell differentiation trajectory analysis, consensus clustering, and LASSO-Cox proportional hazards regression to identify CD8+T-cell subtype-associated prognostic genes. Then we developed and evaluated a risk-score prognostic model and used it to analyze immune infiltration and predict responses to immunotherapy. ResultsWe classified tumor-infiltrating CD8+T-cells in papillary thyroid carcinoma into six subtypes, identified nine prognostic genes (LAIR2, RGS2, DEDD2, HSPA6, KLRB1, DNAJB1, CCL5, CX3CR1, and MT1M), and constructed a prognostic model. Receiver operating characteristic (ROC) curves for the training, validation, and combined cohorts demonstrated that the model had good predictive performance for 3-, 5-, and 10-year overall survival in patients with papillary thyroid carcinoma. Patients in the high-risk group had significantly shorter overall survival than those in the low-risk group (P=0.021) and exhibited lower levels of immune cell infiltration, while the low-risk group showed a higher response rate to immunotherapy (P=0.04). ConclusionThis prognostic model can effectively predict the prognosis, immune infiltration characteristics, and response to immunotherapy in patients with papillary thyroid carcinoma, providing a theoretical basis for clinical prognostic assessment and the development of personalized treatment strategies.
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.
