Search

Multiple primary malignancies in a single patient are relatively rare; however, the frequency of this has increased significantly in recent decades. Here, we retrospectively reported an unusual case of a 70-year-old man who was admitted to the hospital with mantle cell lymphoma (MCL) and colon cancer and aimed to explore measures to reduce missed diagnosis. Based on the data, the investigation of the related literatures, colonoscopy examination, and abdominal computed tomography (CT) scan were conducted for the detection of colon cancer. Following this, a precise diagnosis of MCL was confirmed by immunohistochemistry and bone marrow biopsy, which were performed to analyze the clinical characteristics and essentials for the diagnosis and differential of the disease. The results of colonoscopy showed that the patient had colon cancer, while the abdominal CT scan demonstrated colon cancer accompanied by multiple lymphadenopathy throughout the entire body. Besides, the results of immunohistochemistry confirmed that the patient suffered from MCL. The bone marrow biopsy revealed the active hematopoietic tissue hyperplasia but no tumor issue involvement in the bone marrow. In conclusion, our study combined the analysis and summary of the diagnosis and treatment of the colon cancer with MCL to provide clinical guidance for the rare multiple primary malignancy.

The aim of this study was to evaluate the nutrition and metabolism status alteration during immunotherapy in advanced hepatocellular carcinoma (HCC) patients. Patients with advanced HCC who participated in the clinical trials of single-agent anti-PD-1 immunotherapy or sorafenib were retrospectively included. We analyzed self-comparison of the nutritional and metabolic indices of patients in the anti-PD-1 and sorafenib treatment group. We conducted mutual-comparison of the mentioned indices between the disease progression group and disease control group among anti-PD-1 treatment patients. We further analyzed those indices with statistical differences by partial correlation and survival analysis. Both self-comparison before and after treatment in the anti-PD-1 group and mutual-comparison of disease progression and the control group showed significant differences in multiple indices, but we did not observe significant differences in the sorafenib group. Strikingly, albumin (ALB)/prognostic nutritional index (PNI, calculated by serum albumin and lymphocyte count) decreased distinctly in the immunotherapy disease progression group patients. However, changes in ALB/PNI were not significant in disease progression patients from the sorafenib group or in the disease control patients with immunotherapy. Partial correlation analysis suggested that ALB and PNI were positively correlated with the efficacy of immunotherapy. Furthermore, survival analysis showed that the median progression-free survival and median overall survival of patients in the ALB/PNI decreased group were significantly shorter than those of patients from the ALB/PNI increased group. Anti-PD-1 immunotherapy might alter the nutritional and metabolic status in advanced HCC patients. We also should pay attention to the nutritional and metabolic status of patients when drug resistance is detected.

Colorectal cancer (CRC) is one of the common human malignancies. Discovery and identification of novel therapeutic target is imperative to improve the prognosis of CRC patients. As a member of the PIM family, PIM3 has been found to be overexpressed in a variety of cancerous tumors. In this study, we evaluated the expression of PIM3 in CRC tissues and analyzed the role of PIM3 in CRC. Our results showed that PIM3 expression was significantly higher in CRC tissues compared with adjacent noncancerous tissues. The PIM3 expression level was found to be correlated with advanced disease stage and lymph node metastasis. Moreover, PIM3 was found to be able to predict poor prognosis in CRC patients as an independent factor. In vitro studies also showed that knockdown of PIM3 exhibited inhibitory effect on cell growth, promoted cell apoptosis and dampened invasive capability of HCT116 and SW620 cells. Moreover, PIM3 knockdown was able to delay tumor growth and suppress lung metastasis in xenograft model. Our results indicated that PIM3 is a potential therapeutic target for CRC. Anat Rec, 302:1552-1560, 2019. © 2018 American Association for Anatomy.

F-box and WD repeat domain containing 7 (FBXW7) is a tumor suppressor gene frequently inactivated in several human malignancies. The present study aimed to investigate the role of FBXW7 in the invasion, migration and angiogenesis of ovarian cancer (OC) cells, and to identify its potential molecular mechanisms. First, the expression levels of FBXW7 and vascular endothelial growth factor (VEGF) were detected in several human OC cell lines using western blotting. Subsequently, FBXW7 was overexpressed to determine VEGF expression in SKOV3 cells. Transwell, wound healing and tube formation assays were performed following transfection with FBXW7 and VEGF overexpression plasmids to assess invasion, migration and angiogenesis in SKOV3 cells, respectively. Western blot analysis was performed to detect the expression levels of epithelial-to-mesenchymal transition and angiogenesis-associated proteins. In addition, the expression levels of β-catenin and c-Myc were assessed, and lithium chloride (LiCl), an agonist of β-catenin signaling, was used to elucidate the molecular mechanisms by which FBXW7 mediates its antitumor activity in OC. The results demonstrated that FBXW7 expression was markedly downregulated, whilst VEGF expression was markedly upregulated in OC cell lines compared with that in normal ovarian cells. Overexpression of FBXW7 significantly decreased VEGF expression in SKOV3 cells. Notably, overexpression of VEGF reversed the inhibitory effects of FBXW7 overexpression on the invasion, migration and angiogenesis of OC cells, accompanied by upregulated expression levels of N-cadherin, slug, CD31, VEGF receptor 1 (VEGFR1) and VEGFR2, and downregulated expression levels of E-cadherin. Furthermore, overexpression of FBXW7 markedly suppressed β-catenin and c-Myc expression, whereas the decreased expression levels of VEGF, VEGFR1 and VEGFR2 following overexpression of FBXW7 were increased after treatment of SKOV3 cells with LiCl. Overall, the results of the present study suggested that FBXW7 inhibited invasion, migration and angiogenesis of OC cells by suppressing VEGF expression through inactivation of β-catenin signaling. Thus, FBXW7 may be used as a novel therapeutic target for the treatment of OC.

ObjectiveThis study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.MethodsUsing single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.ResultsA total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood.

Background. Lung cancer (LC) has the highest mortality rate among all the other types of cancer in the world. T cells are known to be the key factor in inducing the immune response during LC. Objective. In this study, we aimed to screen and analyze RNAs associated with CD8(+) T cells and activated memory CD4(+) T cells in lung adenocarcinomas, a subtype of non-small-cell lung cancer (NSCLC-LUAD). Methods. Gene expression RNA-seq data and clinical data of NSCLC-LUAD were downloaded from the XENA database. The data were divided into low scores and high scores based on the Stromal and Immune scores. Then, all the genes were screened for identifying those specifically associated with CD8(+) T cells and activated memory CD4(+) T cells. The screened genes were used for the construction of the protein-protein interaction (PPI) network and for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis along with prognosis analysis. Based on the results of the prognostic analysis, the prognostic-related genes were used to analyze long noncoding (lnc)RNA-micro(mi)RNA-mRNA networks and to predict small chemical molecules. Results. According to the Immune and Stromal scores, a total of 885 upregulated and 29 downregulated RNAs were identified. A total of 90 differentially expressed genes (DEGs) were found to be related to CD8(+) T immune cells, and 48 DEGs were related to activated memory CD4(+) T cells. GPR174 and CD226 suggested a favorable prognosis. For CD8(+) and activated memory CD4(+) T cells, 112 and 113 PPI edges were obtained, respectively. GPR174 was found to be regulated by hsa-miR-19b-5p and hsa-miR-19b-2-5p, and both of these two miRNAs were regulated by lncRNA PCED1B-AS1. CD226 was regulated by hsa-miR-379-5p, which was in turn regulated by lncRNA RP11-81H14.2. Conclusion. Our findings provide a deeper understanding of the T cell-related ceRNA regulatory mechanism in NSCLC-LUAD pathogenesis.

Objective: This study investigated the gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas.Methods: The gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4+ and CD8+ T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted.Results: In total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4+ T cell-related genes and 78 CD8+ T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4+ T cell-related genes, the chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8+ T cell-related genes.Conclusions: The chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4+ and CD8+ T cell infiltration, respectively, in BRCA.

Background: Tumor-infiltrating T cells in the tumor microenvironment are the biological basis of immunotherapy and promising predictors of cancer prognosis. Aim: The aim of this study was to investigate immune‐related RNAs associated with tumor-infiltrating T cells in ovarian cancer (OV).Methods: The gene expression data of patients with OV were downloaded from The Cancer Genome Atlas (TCGA) database. The immune and stromal scores were calculated and the differentially expressed mRNAs (DEGs) were screened. The abundance of six types of infiltrating immune cells was investigated, and the immune-related DEGs associated with tumor-infiltrating CD4+ and CD8+ T cells were explored by correlation analyses. Subsequently, multiple analyses, i.e., protein-protein interaction (PPI) network analysis, competing endogenous RNA (ceRNA; lncRNA-miRNA-target) network analysis, and small-molecule target network analysis, were performed. Results: In total, 37 and 49 immune-related DEGs of CD4+ and CD8+ T cells were screened, respectively. PPI network results showed that granzyme B (GZMB) was a hub node in the two PPI networks constructed by immune-related DEGs of CD4+ and CD8+ T cells. Moreover, the ceRNA chr22-38_28785274-29006793.1/has-miR-1249-5p/CD3E was obtained from the two constructed ceRNA networks related to CD4+ and CD8+ T cells. Survival analysis revealed that key immune-related DEGs of CD4+ and CD8+ T cells, such as GZMB and CD3E, were positively correlated with patient prognosis. Conclusion: GZMB and ceRNAs, such as chr22-38_28785274-29006793.1/has-miR-1249-5p/CD3E, may mediate the role of tumor-infiltrating T cells in OV. GZMB and CD3E may be used as promising T cell-related biomarkers with prognostic value in OV.

Objective: This study aimed to screen the potential molecular targets for proximal, mid, and distal esophageal cancers.Methods: The clinical data, RNA-seq data, and survival data for TCGA esophageal cancer were retrieved from UCSC Xena database. The samples with clinical information on the esophageal tumor central location were selected. Differential analyses on different groups (mid vs. proximal, distal vs. proximal, and distal vs. mid) were performed. Following the differentially expressed genes (DEGs) in three groups were analyzed, the common genes were subjected to survival analysis, miRNA prediction, and drug-gene analysis. The specific genes were annotated for functional and module analyses.Results: Six common genes, namely KCNA1, CCDC196, UNC5CL, CYP3A5, CA10, and REG3A, were analyzed among three comparison groups. The expression of CA10 and REG3A was significantly correlated in the prognosis of patients with esophageal cancer. The distal vs. mid groups screened 766 specific DEGs, and the mid vs. proximal group screened 99 specific DEGs. Functional analysis showed that the genes of distal vs. mid groups, including EDN3, CGA, CCR9, and GABRA2, as well as genes in the mid vs. proximal groups, including GCGR, OXTR, and MCHR2, were significantly enriched in neural functions. In the distal vs. proximal groups, there were 314 specific DEGs, including CYP2C8 and OXGR1.Conclusion: Six common genes may serve as the potential molecular targets for the treatment of all proximal, mid, and distal esophageal cancers.

Additional file 1 Table S1. DEGs between high stromal score vs low stromal score and high immune score vs low immune score.

L-securinine is a natural product extracted and isolated from the leaf of dried Securinega suffruticosa. The aim of the present study was to explore the effects of L-securinine on proliferation, and the methylation profile of the dickkopf-related protein 1 (DKK1) gene in human lung cancer cells and fibroblasts. L-securinine was extracted, isolated and the structure was identified. The cytotoxicity of L-securinine in A549 cells was evaluated by Cell Counting Kit-8 assays. The expression and DNA methylation profile of DKK genes was analyzed by reverse transcription-quantitative polymerase chain reaction and bisulfite sequencing polymerase chain reaction, respectively. L-securinine inhibited the proliferation of lung cancer cells; the half-maximal inhibitory concentration values were 8.92, 4.73 and 3.81 µg/ml, at 24, 36 and 48 h post-treatment, respectively. DKK1, 2 and 3 expression was significantly increased in A549 cells compared with HLF-a cells. L-securinine induced the downregulation of DKK1 in A549 cells in a dose-dependent manner and induced methylation changes at CpG sites in the DKK1 promoter region. L-securinine may be a potential anticancer drug that mediates its effects by altering DKK1 gene methylation.

Tongue diagnosis, as a unique method of traditional Chinese medicine (TCM), was used to discriminate physiological functions and pathological conditions by observing the changes of the tongue and tongue coating. The aims of the present study were to explore a potential screening and early diagnosis method of cancer through evaluating the differences of the images of tongue and tongue coating and the microbiome on the tongue coating. The DS01-B tongue diagnostic information acquisition system was used to photograph and analyze the tongue and tongue coating. The next-generation sequencing technology was used to determine the V2-V4 hypervariable regions of 16S rDNA to investigate the microbiome on the tongue coating. Bioinformatics and statistical methods were used to analyze the microbial community structure and diversity. Comparing with the healthy people, the number of mirror-like tongue, thick tongue coating and the moisture of tongue were increased in cancers. The dominant color of the tongue in the healthy people was reddish while it was purple in the cancers. The relative abundance of Neisseria, Haemophilus, Fusobacterium and Porphyromonas in the healthy people were higher than that in the cancers. We also found 6 kinds of special microorganisms at species level in cancers. The study suggested that tongue diagnosis may provide potential screening and early diagnosis method for cancer.

Background: Abnormal lipid metabolism is considered to be one of main promoters of colorectal cancer (CRC), and intestinal microorganisms may be involved in CRC in patients with abnormal lipid metabolism. Objective: To investigate lipid metabolism in CRC patients and explore the role of intestinal microorganisms in CRC complicated with abnormal lipid metabolism. Methods: Overall, 150 CRC patients in Huzhou Central Hospital from January 2016 to September 2017 were recruited in the present study. Basic patient information and clinical serological indicators were investigated and analyzed. Twenty-one stool samples were collected from patients after receiving informed consent. Next-generation sequencing technology was used to sequence bacterial 16S ribosomal RNA. Bioinformatics analysis was used to profile the microbial composition and screen distinctive bacteria in patients with CRC complicated with abnormal lipid metabolism. Results: Apo B and FFA levels were higher in patients with stage I disease than in patients with other stages. HDL, LDL, Apo B and FFA levels were higher in female patients than in male patients. FFA level was higher in rectal cancer patients than in colon cancer patients. These differences were statistically significant (p

An increasing number of studies have reported that microRNAs (miRNAs) are dysregulated in cervical cancer and serve critical roles in cervical oncogenesis and progression. Therefore, identifying the aberrantly expressed miRNAs implicated in the formation and progression of cervical cancer may provide key clues for the development of effective therapeutic targets in treating patients with this type of malignancy. In the present study, miRNA‑874 (miR‑874) was downregulated in cervical cancer tissues and cell lines, and this downregulation was associated with International Federation of Gynaecology and Obstetrics stage and lymph node metastasis. The restored expression of miR‑874 prohibited the proliferation, migration and invasion, but promoted the apoptosis of cervical cancer cells. In addition, E26 transformation specific‑1 (ETS1) was identified as the direct target of miR‑874 in cervical cancer. Inhibition of ETS1 served tumour‑suppressive roles similar to miR‑874 overexpression in cervical cancer cells. A series of rescue experiments revealed that restoring ETS1 expression abolished the tumour‑suppressing effects of miR‑874 in cervical cancer cells. Taken together, the results of the present study indicated that miR‑874 may serve as a tumour suppressor in cervical cancer by directly targeting ETS1. This function suggested that miR‑874 holds potential therapeutic applications in treating patients with this type of malignancy.

Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies.