The spatial distribution of immune cells in the tumor microenvironment (TME) is a key determinant of immunotherapy response, while current methods are limited by sequencing dependence and restricted spatial resolution. We developed SpaHE-Infil, a multimodal computational framework integrating spatial transcriptomics and whole-slide images to train a Random forest model, extracting morphological, textural, and density features to identify 12 core TME cell types in situ, with dynamic calibration correcting immune cell proportion biases in clinical samples. Cross-cancer validation confirmed its accurate spatial cell distribution prediction, consistent with mIHC and canonical deconvolution algorithms. In clinical cohorts, TME immune infiltration stratification via H&E images predicted enhanced immunotherapy response and prolonged recurrence-free survival across multiple cancers. This framework provides a clinically applicable tool for spatial TME characterization, supporting tumor immunology research, and precision immunotherapy practice.

Background The roles of cancer-associated fibroblasts (CAFs) and disulfidptosis in colorectal cancer (CRC) remain unclear. Methods Using single-cell RNA sequencing (scRNA-seq) and disulfidptosis-related genes (DRGs), we analyzed CRC datasets (TCGA-CRC, GSE87211, GSE132257). CAFs were extracted from scRNA-seq for pseudotime analysis. Differentially expressed genes (DEGs) from scRNA-seq (DEGs1), TCGA-CRC (DEGs2), and DRG-associated weighted gene co-expression network analysis (WGCNA) modules were overlapped to obtain intersecting genes. Prognostic genes and a risk model were constructed using Cox regression and least absolute shrinkage and selection operator (LASSO), followed by functional, immune, and drug sensitivity analyses. Results A total of 47 intersecting genes were generated from 127 DEGs1, 5,535 DEGs2, and 3,627 module genes. Machine learning combined with Cox analysis identified two prognostic genes (SRPX and PRELP). Using optimal and median risk scores, CRC patients were stratified into high- and low-risk groups in TCGA-CRC and GSE87211, with significant survival differences observed between the two groups (P < 0.05). M0 macrophages showed positive correlations with risk score (r = 0.36) and PRELP (r = 0.44), while activated CD4 + memory T cells showed negative correlations with risk score (r = -0.27) and PRELP (r = -0.3). Pseudotime analysis revealed CAF subpopulations distributed across three distinct differentiation pathways, with CAF_infa and CAF_PN enriched in early stages, followed by CAF_myo, CAF_AP, and CAF_adi. Conclusions Collectively, both SRPX and PRELP are associated with DRGs and CAFs, offering a new perspective for CRC diagnosis and treatment.

The effect of immunotherapy for colorectal cancer (CRC) is limited due to anti-tumor immunosuppression. Circular RNAs (circRNAs) are also associated with tumor immunity. The aim of this study was to clarify the regulatory relationship between circRNA and anti-tumor immunosuppression in CRC. CircRNAs associated with CRC were identified using bioinformatic analysis and subsequently confirmed in clinical samples using qRT-PCR and in situ hybridization. The expression, clinical relevance, functional significance and clinical properties of circMVP in CRC specimens and cells were evaluated in vitro and in vivo. RNA pull-down, single-cell RNA sequencing, EMSA, RNA immunoprecipitation, chromatin immunoprecipitation, and polysome profiling assay were performed to confirm the underlying mechanism of circRNA. CircMVP (hsa_circ_0000688) expression was increased in CRC and correlated with poor prognosis in CRC patients. Increased circMVP expression activates proliferation, invasion, and tumorigenesis of CRC. In addition, we found that circMVP, by interacting with METTL3, stabilizes its expression in the nucleus and significantly enhances its mediated N6-methyladenosine (m6A) modification. Specifically, circMVP/METTL3 promoted the expression of (3-catenin by directly acting on CTNNB1 mRNA. CircMVP/METTL3 further enhanced the expression of B7-H3 through the (3-catenin signaling pathway. Notably, inhibition of circMVP expression significantly improved the efficacy of anti-B7-H3 immunotherapy in in vivo and in vitro models. CircMVP mediated CTNNB1 m6A modification by promoting METTL3 activation and inhibited B7-H3-dependent anti-tumor immune response in CRC. In conclusion, circMVP may be a predictor of CRC immune evasion and a potential therapeutic target.

Colorectal cancer (CRC) is characterised by microbial dysbiosis. Trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) are gut microbiota-derived metabolites produced from dietary precursors that are implicated in CRC progression. However, the underlying mechanisms by which TMA or TMAO affect CRC progression remain largely unexplored. Therefore, in this study, we aimed to investigate the effects of TMA and TMAO on CRC progression. The methods used included real-time PCR, western blotting, cell viability and migration assays, apoptosis analysis, single-cell RNA sequencing, and tumor xenograft models. We demonstrated that exposure to both TMA and TMAO promoted CRC cell proliferation. Notably, treatment with 1 μM TMA and 100 μM TMAO had the greatest effect on enhancing CRC cell invasion and migration, while also reducing apoptosis. Mechanistically, TMA and TMAO modulated the expression of sterol regulatory element-binding factor 1 (SREBF1) and activated the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signalling pathway, thereby contributing to CRC progression. In mouse subcutaneous tumour experiments, a high-TMAO diet accelerated CRC progression, leading to significantly larger tumour volumes than those in the control group. Collectively, these findings suggest a potential correlation between elevated serum TMAO levels and CRC progression. Notably, we provide the first evidence that TMA and TMAO promote CRC cell proliferation via activation of the PI3K/AKT signalling pathway, with SREBF1 serving as a key mediator of TMA- and TMAO-induced CRC proliferation. Reducing TMA and TMAO intake through dietary intervention and the use of SREBF1 inhibitors may delay CRC progression, offering considerable clinical potential for therapeutic applications.

Colorectal cancer (CRC) is characterized by poor responsiveness to immune evasion and immunotherapy. RNA 7-methylguanine (m7G) modification plays a key role in tumorigenesis. However, the mechanisms by which m7G-modified RNA metabolism affects tumor progression are not fully understood, nor is the contribution of m7G-modified RNA to the CRC immune microenvironment. The expression levels of Methyltransferase-like 1 (METTL1) and m7G in human tissues were determined. In this study, the effect of METTL1 on RNA m7G levels was evaluated, the effect of METTL1 on PKM mRNA modification was confirmed, the expression level of the PKM2 protein was detected, and the mechanism involved RT‒qPCR, Western blot, RNA stability analysis and RIP analysis. Lactate and H3K9 lactylation (H3K9la) induced by METTL1/PKM2 were analyzed via the extracellular acidification rate (ECAR) and lactic acid assays. Cut Run was used to detect METTL1/PKM2-induced CD155 (PVR) transcription. In addition, METTL1 knockout mice were studied in vivo with CD155 blockers. We demonstrated that m7G RNA METTL1 enhances PKM2 expression by acting on PKM mRNA, leading to tumor progression and increased glycolysis. Specifically, METTL1 mediates m7G methylation of PKM mRNA and enhances the expression of its encoded PKM2, which in turn enhances glycolysis, promotes H3K9la, and activates METTL1 transcription, creating a positive feedback loop. Moreover, increased PKM2 dimer expression and nuclear translocation activated CD155 expression and induced CRC immune evasion. Our findings reveal a general mechanism by which METTL1/PKM2/H3K9la signaling regulates RNA metabolism and highlight METTL1 targeting as a potential strategy for CRC immunotherapy.

Background: Cancer-associated fibroblasts (CAFs) are principal constituents of the tumor microenvironment (TME) and play a critical role in tumor progression. The CXCL12/CXCR4 axis regulates multiple facets of the TME. The aim of this study was to determine the relationship between CXCL12 expression in CAFs and the malignant progression of gastric cancer (GC). Methods: In the GEO (Gene Expression Omnibus) database, we performed transcriptome analysis on paired gastric cancer RNA sequencing samples, and scRNA analysis was performed on advanced malignant GC samples from the scRNA sequencing data set. Fibroblast cells were co-cultured with GC cells, and invasion, migration, epithelial-mesenchymal transformation (EMT) were determined. After blocking the expression of fibroblast CXCL12, cells were co-cultured with a GC cell line. Detection of GC cell line invasion, migration, EMT and CXCR4, Wnt5a and β-Catenin expression levels was performed. Primary CAFs and gastric normal fibroblasts were isolated and CXCL12 mRNA and protein expression were determined. In addition, a cohort of 285 GC cases was established, protein expression was evaluated immunohistochemically, and prognostic results were analyzed. Results: GC transcriptome analysis suggested that cytokine-cytokine receptor interaction and the Wnt signaling pathway in GC tissues were significantly up-regulated. scRNA analysis of advanced malignant GC samples showed that severe intestinal metaplasia (SIM) in GC specimens of different malignant grades had obvious fibroblast clusters compared to non-atrophic gastritis (NAG) and early gastric cancer (EGC). In the SIM group, fibroblast cluster, CXCL12, CXCR4, and Wnt5a were overexpressed. Co-culturing with fibroblast cells significantly increased the invasion, migration, and EMT of GC cells, and blocking CXCL12 in CAFs disturbed the expression of Wnt5a and β-catenin. In our cohort of GC patients, high CXCL12 expression in CAFs significantly correlated with histological grade (P = 0.012) and TNM stage (P = 0.014), as well as with poor overall survival (p = 0.0107). Conclusion: High expression of CXCL12 in CAFs in a GC microenvironment can affect the migration, invasion, and EMT of GC cells. Furthermore, it can cause poor prognosis in patients with GC.

Background: miRNA expression data on colorectal cancer (CRC) are constantly updated. Therefore, integrated analysis of these datasets prior to experiments is necessary in translational medicine and oncology research. Abnormal low expression of hsa-miRNA-215-5p (miR-215) is detected in several cancer types, but the role of miR-215 in CRC remains unclear. Therefore, the aim of this work was to identify the expression and role of miR-215 involved in CRC. Methods: An integrated analysis of 4 sets of miRNA microarray data of CRC in GEO was implemented. The low expression of miR-215 in CRC was confirmed by TCGA datasets. In addition, frozen tissue and paired formalin-fixed paraffin-embedded samples were collected from 214 CRC patients who underwent CRC surgery at the Affiliated Hospital of Jiangnan University, China, and used as an independent clinical validation study. Furthermore, colon cancer cells HCT116 and SW480 transfected with miR-215 mimic/inhibitor were used to evaluate its mechanism of action and to perform experiments to confirm our results obtained from human samples. Results: CRC patients with a decreased miR-215 expression in adenocarcinoma tissues had a significantly poor prognosis with lower cumulative survival as revealed by the TCGA-COAD dataset. In our 214 CRC patients cohort study this result was confirmed and it was also found that low miR-215 expression was inversely correlated with the expression of IK beta-alpha. Downregulation of miR-215 in HCT116 and SW480 cells resulted in an upregulation of TRAF5 and TAK1 protein expression, and interfered with IK beta-alpha protein expression. Furthermore, with the inhibition of miR- 215, important Epithelial-Mesenchymal Transition (EMT) biomarker proteins were significantly upregulated in HCT116 and SW480 cells. Moreover, an inhibition was obtained using miR-215-mimic. Conclusions: Our integrated microRNA dataset approach identified miR-215 as an independent factor associated with the prognosis of CRC patients. In addition, our results demonstrated that miR-215 might be considered as a potential biomarker for poor prognosis in CRC patients and its role as a potent suppressor of IK beta-alpha and TRAF5.

OBJECTIVE:MicroRNA-384 (miR-384) has been reported to function as a tumor suppressor in multiple cancers; however, its role in gastric cancer (GC) remains unclear.METHODS:We measured expression levels of miR-384 in GC cell lines and in a normal gastric cell line (GES-1). The association between miR-384 and the metadherin gene ( MTDH) was assessed by luciferase reporter assay and western blot. The effects of the miR-384/MTDH axis on GC cell behaviors were measured by CCK-8, wound-healing, and transwell invasion assays.RESULTS:miR-384 was significantly downregulated in GC cell lines compared with normal gastric cells. MTDH was identified as a direct target of miR-384 by bioinformatics analysis, luciferase assay, and western blot. Functional assays demonstrated that miR-384 inhibited GC cell proliferation, migration, and invasion through targeting MTDH.CONCLUSION:These results reveal that miR-384 acts as a tumor suppressor in GC and suggest that the miR-384/MTDH axis may be a potential therapeutic target for GC.

OBJECTIVE: Increasing evidence has indicated an association between gut microbiota in gastrointestinal cancer and clinical outcome. Herein, we aim to develop a prognosis-prediction tool based on an immune-lipid metabolism signature, tumor cell-associated immune microenvironment, and lipid metabolism proteins inferred from the function of gut microbiota. METHODS: 16S gene ribosomal RNA sequencing was performed on 10 fecal samples obtained after tumor resection but before chemotherapy (EBVaGC = 4 and EBVnGC = 6). Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to screening for highly accurate marker proteins. A compound score based on the fraction of screened markers was then constructed using a LASSO logistic regression model. RESULTS: The Tax4Fun analysis based on Kyoto Encyclopedia of Genes and Genomes data indicated differentially expressed tumor pathway between EBVnGC and EBVaGC. Using the LASSO logistic model, a compound score was established consisting of 14 types of immune microenvironment and lipid metabolism proteins. In the training set (378 patients), significant differences were found between high- and low-compound score groups in overall survival across and within subpopulations with an identical EBV. Multivariable analysis revealed that the compound score was an independent prognostic factor (hazard ratio, 2.26; 95% confidence interval = 2.28–3.36). The prognostic value ;of the compound score was also confirmed in the validation (162 patients) and entire (540 patients) sets. DISCUSSION: The proposed compound score is a promising signature for estimating overall survival in patients with gastric cancer having EBVaGCs or EBVnGCs.

Background: We made investigations on the expression of negative costimulatory molecules B7-H1, B7-H3, B7-H4 in lesions at various stages of human colorectal cancer (CRC) evolution. We also analyzed the relevance between its expression in CRC and pathological factors in clinic and patient survival time. We finally made a result that we can ensure the clinical significance of B7-H3, B7-H4 expression and the relationship between the B7 family molecules expression. Methods: All stages of CRC were collected, including polyps, adenomas, high-grade neoplasms, and colorectal carcinomas. There were 98 cases of resected CRC tissue, 30 cases of polyps, 30 cases of adenomas, and 25 cases of high-grade neoplasia. Then analysis the expression of three negative costimulatory molecules in all stages of colorectal tissue expression patterns, flow cytometry CD3(+) T lymphocytes B7 family molecules to explore the potential value of their expression. Results: The expression of B7 family molecules in 30 cases of polyps, 30 cases of adenomas, 25 cases of high-grade neoplasia, and 98 cases of CRC tissues revealed that the B7-H1 and B7-H3 expression quantity was found in polyps, adenomas, high-grade neoplasms, as well as they were highly expressed in cancerous tissues. B7-H4 was only expressed in cancerous tissues. In the TNM stage of tumor progression, three negative costimulatory molecules were mainly expressed in the cytoplasm of tumor cells. In CRC in lymphocytes B7-H4 expression was related to patient age, mucinous adenocarcinoma, and lymph node metastasis. Survival analysis showed in CRC it was statistically significant that that the expression of B7-H3 and the survival rate of patients. We found that 92.9% of CRC patients expressed B7 family negative costimulatory molecules in varying degrees, and the prognosis and co-expression of B7 family negative co-stimulatory molecules were negatively correlated. Conclusions: Costimulatory molecules B7-H1, B7-H3 were expressed on the early stage of CRC development. The amount of CD3(+) T lymphocyte infiltration in CRC was positively correlated with the survival of patients. They are the earliest molecules to participate in the progress of CRC developing in B7 family negative molecules. This suggests that B7-H1 and B7-H3 are involved in rectal carcinoma at the junction, as well as it is essential throughout the entire evolutionary process. However, it is in CRC tissues that B7-H4 only get expressed, and different expression patterns may have different clinical significances.

The human enhancer of filamentation 1 (HEF1) is a multi-domain docking protein of the p130 Cas family. Research reports on the mechanism of HEF1 in gastric cancer (GC) differentiation are limited. In this study, we reveal that HEF1 plays an essential role in regulating of differentiation in human GC. HEF1 was found to be highly expressed in GC tissues. Besides, In GC tissues or cells, cellular level of HEF1 negatively correlated with tumor differentiation. In addition, we showed that upregulation of HEF1 increased Wnt5a expression and the nuclear translocation of β-catenin, thereby resulting in poor differentiation in GC. Notably, GC patients with a higher expression of HEF1 showed significantly poorer disease-free and overall survival. Thus, our findings suggest that HEF1 reduces differentiation through the Wnt5a/β-catenin signaling pathway and that HEF1 is an independent unfavorable prognostic death factor in GC.

The protein-coding gene adenosine monophosphate deaminase (AMPD) 2 plays a critical role in energy metabolism by converting adenosine-5-monophosphate (AMP) to iosine inosine-5-monophosphate (IMP). Obesity affects metabolic abnormalities in tumor cells and has been associated with high expression levels of AMPD2 and colorectal cancer (CRC). In this study, we performed immunohistochemical analysis of AMPD2 expression in 158 patients with CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine AMPD2 mRNA expression levels, which were validated by The Cancer Genome Atlas (TCGA) datasets. Chi-square test and Fisher's exact test were used to evaluate the correlation between the expression of AMPD2 and clinicopathological parameters of CRC. Overall survival (OS) rates of the CRC patients were calculated using Kaplan-Meier survival analysis and a Cox proportional regression model was performed for univariate and multivariate analysis. A logistic regression model was used to plot the receiver operating characteristic (ROC) curve and to evaluate the predictive effect of multivariate studies on prognosis outcomes of CRC. We found a significant increase in AMPD2 expression in tumor tissue (91.8%, 146/158) compared to adjacent normal tissue (52.5%, 83/158, P < 0.01). The positive rate of AMPD2 expression was 72.7% (39/54) in overweight individuals versus 51.9% (54/104) in individuals with a normal weight (P = 0.014). AMPD2 mRNA levels as determined by qRT-PCR elevated levels of AMPD2 transcripts were higher in CRC samples compared to adjacent normal tissues (P < 0.05). In both the TCGA colon adenocarcinoma and rectal adenocarcinoma dataset, the number of CRC patients with increased levels of AMPD2 in tumor tissues was significantly higher compared to patients with adjacent normal tissue (P < 0.001). High expression of AMPD2 was associated with TNM stage, higher histological grade, obesity, and lower OS rates in patients with CRC. Obesity and high expression of AMPD2 in patients are with poor prognosis. Moreover, multivariate analysis indicated that AMPD2 levels and TNM stage were significant independent prognostic factors in CRC patients. The logistic regression predictive effect of the area under the curve (AUC) was 0.821 (P < 0.001). In conclusion, high levels of AMPD2 and obesity are associated with poor prognosis in patients with CRC.

AIM:To investigate the expression and clinical significance of B7 homolog 3 (B7-H3) and β-1,3-galactosyltransferase-4 (B3GALT4) in colorectal cancer (CRC) patients. METHODS:Using tissue microarray, we identified the expression of B7-H3 and B3GALT4 in 223 CRC patient samples by immunohistochemistry and evaluated the possible correlation between B7-H3 and B3GALT4 and clinical outcomes. Further, the mRNA and protein expression were identified to establish the regulatory relationship of B7-H3 with B3GALT4 in vitro. RESULTS:A significant positive correlation between B7-H3 and B3GALT4 was observed in CRC specimens (r = 0.219, P = 0.001). High expression of B7-H3 was identified as a significant independent predictor of poor overall survival (OS) [hazard ratio (HR) = 1.781; 95%CI: 1.027-3.089; P = 0.040]. Moreover, high expression of B3GALT4 was also recognized as an independent predictor of inferior OS (HR = 1.597; 95%CI: 1.007-2.533; P = 0.047). Additionally, CRC patients expressing both high B7-H3 and high B3GALT4 contributed to a significant decrease in OS (HR = 2.283; 95%CI: 1.289-4.042; P = 0.005). In CRC cell lines with stable expression of high B7-H3, the mRNA and protein expressions of B3GALT4 were significantly upregulated. Similarly, the expression of B3GALT4 was significantly reduced when expression of B7-H3 was knocked down. CONCLUSION:The expression of B3GALT4 in CRC is positively correlated with B7-H3 expression in vitro. B7-H3/B3GLAT4 may be used as dual prognostic biomarkers for CRC.

Cytochrome P450 1B1 (CYP1B1) is a phase I xenobiotic-metabolizing enzyme (XME) that is overexpressed in colorectal cancer (CRC) tissue, but the prognosis value of CYP1B1 in CRC remains elusive. Additionally, B7-H3 has a key role in tumor cell immune evasion by inhibiting functions of T cells. Thus, in this study, we aimed to identify a new marker for predicting the prognosis of CRC and to study the relationship between tumor metabolism and tumor immunity. We analyzed CYP1B1 and B7-H3 expression in 231 patients with CRC using immunohistochemistry, and we investigated the relationship between CYP1B1 and B7-H3 expression using real-time PCR and Western blot analysis in two human CRC cell lines. Kaplan-Meier survival analysis was used to calculate overall survival (OS) rates, and Cox proportional regression model was performed for multivariate analysis. We found that both CYP1B1 and B7-H3 expression were aberrantly increased in CRC tissues compared to normal colorectal tissues. Moreover, high expression of CYP1B1 was significantly correlated with poor OS, and multivariate analysis indicated that CYP1B1 was a valuable independent prognostic biomarker. Furthermore, CYP1B1 expression was significantly correlated with B7-H3 expression in CRC tissues samples and two human CRC cell lines. In conclusion, these results indicate that CYP1B1 may be a novel predictive biomarker for prognosis of CRC patients, and there is a strong correlation between CYP1B1 and B7-H3 in vivo and in vitro.

Objective To examine the expression of chemokine receptor type 5 (CXCR5) in colorectal cancer (CRC) and to explore its relationship with clinicopathological features and cell proliferation in CRC.Methods Immunohistochemical staining method was used to detect the protein expression of CXCR5 in 132 paired specimens of CRC,adjacent and 62 samples of adenoma.Analysing the relationship between CXCR5 with clinicopathological features in CRC.RNA interference (RNAi) technique was applied to construct four CXCR5 short hairpin RNA (shRNA) expression vectors.Lipofectamine 2000 was used to transfer plasmids into colon cancer cell lines LoVo and HCT116.Real-time PCR and Western blotting were used to observe the inhibitory effect of RNAi on CXCR5 expression.Lentivirus production and transduction were used to construct CXCR5 shRNA stably expressed CRC cell lines.CXCR5 overexpressed plasmid was used to construct CXCR5 stably expressed CRC cell lines.cell counting kit-8 (CCK-8) assay and colony formation assay were used to detect the influence of specific CXCR5 on CRC cell.Tumor formation in nude mouse was performed to detect the effects of CXCR5 on the proliferation ability of CRC cells in vivo.FCM were used to detect the cell cycle.Results CXCR5 protein was expressed in 46.97％ (62/132) of CRC tissues and 24.19％ (15/62) of adenoma tissues,respectively.The protein expression of CXCR5 was negative in adjacent tissues.The protein expression level of CXCR5 in CRC tissues was significantly higher than ademona tissues (P =0.020).The expression of CXCR5 was correlated with relapse,TNM stage,lymph node metastasis and distant metastasis (P =0.004,0.025,0.002,0.008).CCK-8 and colony formation results showed that the CXCR5 shRNA inhibited the proliferation of CRC significantly,whereas overexpression of CXCR5 promoted CRC proliferation in vitro.Tumor formation results in nude mouse showed that CXCR5 silencing inhibited the proliferation and metastasis ability of CRC cells,whereas overexpression of CXCR5 promoted proliferation of CRC cells in vivo.CXCR5 may influence CRC cells proliferation through cell cycle in vitro.Conclusion CXCR5 may play a crucial role in carcinogenesis,development of CRC.CXCR5 could promote proliferation of colon cancer cell both in vitro and in vivo,and may influence CRC development through cell cycle.

Acyl-CoA thioesterase 1 (ACOT1) is an important isoform of the ACOT family that catalyzes the reaction of fatty acyl–CoAs to CoA-SH and free fatty acids. Recent studies of gastrointestinal tumor metabolism suggest that there is abnormal metabolism of lipids and fatty acids during tumor progression. However, the function and contribution of ACOT1 in gastric cancer development are still poorly understood. In addition, GLI3 is a major transcription factor in the regulation of hedgehog signaling. GLI3 mutations induce glandular expansion and intestinal metaplasia in gastric cancer, which indicates a role for GLI3 in the preneoplastic process. Thus, we investigated the relationship between ACOT1 expression and GLI3 in gastric adenocarcinoma. A tissue microarray was constructed from 280 cases of gastric adenocarcinoma. The immunohistochemistry method was performed on tissue sections of 4 μm from each tissue microarray block. We found a significant correlation between ACOT1 expression and poor histologic grade, a lower T category, TNM stage, and increased GLI3 expression. In addition, the survival analysis revealed that the ACOT1-positive group had significantly decreased overall survival rates compared with the ACOT1-negative group. Furthermore, GLI3 expression had a significant positive correlation with ACOT1 expression in gastric adenocarcinoma cells. In summary, these findings demonstrate that increased expression of ACOT1 is correlated with pivotal clinicopathological parameters and poor prognosis in gastric adenocarcinoma through increased expression of the potential tumor-promoting protein GLI3.

Background Long non-coding RNAs (lncRNAs) have essential regulatory function, yet their roles in colorectal cancer (CRC) are not well understood. Materials and methods Microarray was applied to detect lncRNAs expression profiles in tumor tissues, liver metastasis and paired adjacent normal tissues of CRC. And using RT-PCR to verify chip results. Results A total of 10 680 lncRNAs demonstrated differential expressions (fold change ≥2) between tumor tissues and adjacent normal tissues; furthermore there were 2970 lncRNAs, which showed different expression level between CRC tissues with liver metastasis and adjacent normal tissues. Especially, lncRNA-AK098783 expression level was frequently higher in cancerous tissues than corresponding noncancerous tissue. Higher AK098783 expression was significantly correlated with shortened overall survival (P < 0.001) and distant metastasis (P < 0.001). Conclusions Our results suggest that AK098783 is involved in distant metastasis and dramatically associated with poor prognosis in patients with CRC.

Background/Aims: Aberrant expression of microRNAs (miRNAs) is found to be responsible for tumorigenesis, cancer development and chemoresistance. Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), CRC cells can develop some mechanisms to evade oxaliplatin-induced cell death. It is urgent to explore the novel strategies to increase the chemosensitivity of CRC cells. Methods: QRT-PCR analysis was performed to detect the expression of miR-135b in CRC patients’ serum and CRC cell lines. MTT assays were used to evaluate the effect of anti-miR-135b on oxaliplatin-induced cell death in CRC cell lines. Western blot, flow cytometry and luciferase reporter assays were performed to evaluate the potential mechanism and pathway of anti-miR-135b-promoted apoptosis in oxaliplatin-treated CRC cells. Results: Significant upregulation of miR-135b was observed in CRC cell lines and CRC patients’ serum. Knockdown of miR-135b was found to sensitize colorectal cancer cells to oxaliplatin-induced cytotoxicity. Mechanically, knockdown of miR-135b increased the expression level of FOXO1 in CRC. As the downstream, the increased FOXO1 induced by anti-miR-135b promoted the expression of Bim and Noxa. Since Bim and Noxa act as key pro-apoptotic proteins in mitochondrial apoptosis, anti-miR-135b was able to enhance the oxaliplatin-induced apoptosis dependent on the anti-miR-135b/FOXO1 axis. Conclusions: Anti-miR-135b enhanced the anti-tumor effect of oxaliplatin on CRC. Combination with miR-135b antisense nucleotides may represent a novel strategy to sensitize CRC to oxaliplatin-based treatment.

Background: B7-H3 is an immuno-stimulatory glycoprotein that is overexpressed in cancer. However, its functional contributions to cancer development and progression are not well understood. In several reports, it was demonstrated that B7-H3 reprograms lipid metabolism and regulates glucose metabolism. Isocitrate dehydrogenase 1 (IDH1), a metabolic enzyme in the TCA cycle, its reaction product is involved in lipid synthesis. Thus, we aimed to identify a novel marker to predict the prognosis of CRC patients and to investigate the relationship between IDH1 and B7-H3. Methods: We analyzed IDH1 and B7-H3 expression levels in 225 CRC specimens by immunochemistry. Moreover, in vitro studies were performed to demonstrate the correlation between IDH1 and B7-H3. Results: Among 225 tissues, the positive rates of IDH1 and B7-H3 were 37.8% (85/225) and 87.6% (197/225), respectively. In CRC samples, IDH1 significantly correlated with B7-H3 expression (P = 0.044). Moreover, multivariate analyses revealed that high expression of both B7-H3 and IDH1 and a high tumor grade were related to the prognosis of CRC patients. Kaplan-Meier survival analysis revealed that patients with co-expression of IDH1 and B7-H3 had a poor overall survival. In SW480-B7-H3-EGFP cells, which highly express B7-H3, IDH1 was up-regulated. Similarly, knockdown of B7-H3 expression in Caco-2-shB7-H3 contributed to reduced IDH1 levels. Conclusions: Although IDH1 and B7-H3 cannot be used as independent prognostic factors, co-expression of IDH1 and B7-H3 significantly correlated with the prognosis of CRC patients and may serve as a combined predictive marker. Thus, the correlation between IDH1 and B7-H3 has been proven in vivo and in vitro. (C) 2018 Published by Elsevier Ltd.