Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.

SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

Progress of research on molecular targeted therapies for colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies, accounting for approximately 10% of global cancer incidence and mortality. Approximately 20% of patients with CRC present metastatic disease (mCRC) at the time of diagnosis. Moreover, up to 50% of patients with localized disease eventually metastasize. mCRC encompasses a complex cascade of reactions involving multiple factors and processes, leading to a diverse array of molecular mechanisms. Improved comprehension of the pathways underlying cancer cell development and proliferation, coupled with the accessibility of relevant targeted agents, has propelled advancements in CRC treatment, ultimately leading to enhanced survival rates. Mutations in various pathways and location of the primary tumor in CRC influences the efficacy of targeted agents. This review summarizes available targeted agents for different CRC pathways, with a focus on recent advances in anti-angiogenic and anti-epidermal growth factor receptor agents, BRAF mutations, and human epidermal growth factor receptor 2-associated targeted agents.

Systematic analyzing a five- miRNA panel and its diagnostic value of plasma expression in colorectal cancer.

BACKGROUND: Aberrant expression of miRNAs have been implicated in cancers, but the role of miRNAs in colorectal cancer (CRC) remains need to be elucidated. This study aimed to identify miRNAs that related to colorectal cancer (CRC) pathogenesis and determine the diagnostic value. METHODS: Three GEO datasets (GSE128449, GSE35602 and GSE49246) with 131 samples were used to screen miRNAs that differential expression between tumor and control tissues. The expression of the identified miRNAs was validated in 50 clinical tissue samples and the GSE35834 dataset. The clinical significance of these miRNAs was analyzed in the TCGA dataset and clinical tissue samples. The expression of miRNAs in tissues and plasma samples were tested by RT-PCR assay in clinical samples, and their diagnostic value was determined. RESULTS: The analysis of three GEO datasets revealed that miR-595 and miR-1237 were upregulated, while miR-126, miR-139, and miR-143 were downregulated in CRC tissues compared to control tissues. The differential expression of the five miRNAs in CRC tissues was confirmed using clinical tissue samples and GEO databases. There was no significant correlation between the TNM stage and tumor stage of CRC and any of the five miRNAs. Plasma expression of the miRNAs differed significantly between CRC and non-cancer patients, and each miRNA had moderate diagnostic value for CRC. Combining the five miRNAs provided better diagnostic potential for CRC than a single miRNA. CONCLUSIONS: This study demonstrated that five miRNAs were related to the pathogenesis of CRC, but independent of the stage of CRC; Plasma expression of these miRNAs have moderate diagnostic value, and combination of these miRNAs showed better diagnostic ability in CRC.

Homologous recombination repair gene mutations in colorectal cancer favors treatment of immune checkpoint inhibitors.

Immune checkpoint inhibitor (ICI) therapy is insensitive for Colorectal cancer (CRC) patients with microsatellite stable (MSS). Genomic data of three CRC cohort, n = 35), and the Cancer Genome Atlas (TCGA CRC cohort, n = 377), were analyzed. A cohort treated with ICIs from Memorial Sloan Kettering Cancer Center (MSKCC CRC cohort, n = 110) and two cases from the local hospital were characterized the impact of the HRR mutation on prognosis of CRC. Homologous recombination repair (HRR) gene mutations were more common in CN and HL cohorts (27.85%; 48.57%) than in TCGA CRC cohort (15.92%), especially in the MSS populations, the frequencies of HRR mutation were higher in CN and HL cohort (27.45%, 51.72%) than in TCGA cohort (6.85%). HRR mutations were associated with high tumor mutational burden (TMB-H). Although HRR mutation uncorrelated with an improved overall survival in the MSKCC CRC cohort (p = 0.97), HRR mutated patients had a significantly improved OS compared to the HRR wildtype population particularly in MSS subgroups (p = 0.0407) under ICI treatment. It probably contributed by a higher neoantigen and increased CD4+ T cell infiltration which found in the TCGA MSS HRR mutated CRC cohort. The similar phenomenon on cases was observed that MSS metastatic CRC patient with HRR mutation seemed more sensitive to ICI after multi-line chemotherapy in clinical practice than HRR wildtype. This finding suggests the feasibility of HRR mutation as an immunotherapy response predictor in MSS CRC, which highlights a potential therapeutic approach for these patients.

Bacteria-Loaded Gastro-Retention Oral Delivery System for Alcohol Abuse.

Alcohol abuse is harmful to human health, and many strategies have been developed to retard this harm through protecting liver or activating relative enzymes. In this study, a new strategy of decreasing the alcohol absorption directly depending on the dealcoholization by the bacteria in the upper gastrointestinal (GI) tract was reported. To realize this, a bacteria-loaded gastro-retention oral delivery system with pore structure was constructed through emulsification/internal gelation, which could relieve acute alcohol intoxication in mice successfully. It was found that this bacteria-loaded system kept the above 30% suspension ratio in the simulated gastric fluid for 4 min, displayed good protection effect for the bacteria, and decreased the alcohol concentration from 50 to 30% below within 24 h in vitro. The in vivo imaging results demonstrated that it remained in the upper GI tract until 24 h and reduced 41.9% alcohol absorption. The mice with oral administration of the bacteria-loaded system were found with normal gait, smooth coat, and less liver damage. Although the intestinal flora distribution was influenced slightly during the oral administration, it could restore to normal levels only one day after stopping oral administration quickly, suggesting good biosafety. In conclusion, these results revealed that the bacteria-loaded gastro-retention oral delivery system might intake alcohol molecules rapidly and has huge potential in the treatment of alcohol abuse.

Construction and Validation of an Oxaliplatin-Resistant Gene Signature in Colorectal Cancer Patients Who Underwent Chemotherapy.

Aberrant expression of genes contributes to the chemoresistance of colorectal cancer (CRC) treatment. This study aimed to identify genes associated with the chemoresistance of oxaliplatin-based chemotherapy in CRC patients and to construct a signature. Oxaliplatin resistance-related genes were screened by analyzing the gene profiles of cell lines and tissue samples that underwent oxaliplatin-based treatment. Oxaliplatin resistance-related genes were used to establish a signature. The association of the signature had clinical significance, so the prognostic value of the signature was analyzed. Independent cohorts and CRC cell lines were used to validate the value of the gene signature and the oxaliplatin-resistant genes. There were 64 oxaliplatin resistance-related genes identified after overlapping the genes from the dataset of oxaliplatin-treated CRC cells and the dataset of patients treated with oxaliplatin-based chemotherapy. A gene signature based on five oxaliplatin resistance-related genes was established. This gene signature effectively predicted the prognosis of CRC patients who underwent chemotherapy. No significant associations were found between the gene mutations and survival of the patients; however, two genes were associated with microsatellite instability status. Two external independent cohorts and CRC cell line experiments validated the prognostic values of the signature and expression of the genes after oxaliplatin treatment. In conclusion, the oxaliplatin resistance-related gene signature involving five genes was a novel biomarker for the prediction of the chemotherapy response and prognosis of CRC patients who underwent oxaliplatin-based chemotherapy.

Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy.

Background: Chemotherapy is the basic treatment for colorectal cancer (CRC). However, colorectal cancer cells often develop resistance to chemotherapy drugs, leading to recurrence and poor prognosis. More and more studies have shown that the Homologous recombination (HR) pathway plays an important role in chemotherapy treatment for tumors. However, the relationship between HR pathway, chemotherapy sensitivity, and the prognosis of CRC patients is still unclear. Methods: We collected 35 samples of CRC patients after chemotherapy treatment from Guangxi Medical University Cancer Hospital, then collected mutation data and clinical prognosis data from the group. We also downloaded Mondaca-CRC, TCGA-CRC cohorts for chemotherapy treatment. Result: We found that HR mutant-type (HR-MUT) patients are less likely to experience tumor metastasis after receiving chemotherapy. Additionally, our univariate and multivariate cox regression models showed that HR-MUT can be used as an independent predictor of the prognosis of chemotherapy for CRC patients. The KM curve showed that patients with HR-MUT CRC had significantly prolonged overall survival (OS) time (log-rank p = 0.017; hazard ratio (HR) = 0.69). Compared to HR mutant-type (HR-WT), HR-MUT has a significantly lower IC50 value with several chemotherapeutic drugs. Pathway enrichment analysis further revealed that the HR-MUT displayed a significantly lower rate of DNA damage repair ability, tumor growth, metastasis activity, and tumor fatty acid metabolism activity than HR-WT, though its immune response activity was notably higher. Conclusion: These findings indicate that HR-MUT may be a relevant marker for CRC patients receiving chemotherapy, as it is closely related to improving OS time and reducing chemotherapy resistance.

Clinical Significance and Prognostic Value of the Maximum Standardized Uptake Value of 18F-Flurodeoxyglucose Positron Emission Tomography-Computed Tomography in Colorectal Cancer.

BACKGROUND: The role of 18F-flurodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) in colorectal cancer (CRC) remains unclear. This study aimed to explore the association of the maximum standardized uptake value (SUVmax), a parameter of 18F-FDG PET/CT, with KRAS mutation, the Ki-67 index, and survival in patients with CRC. METHODS: Data of 66 patients with CRC who underwent 18F-FDG PET/CT was retrospectively collected in our center. The clinical significance of the SUVmax in CRC and the association of the SUVmax with KRAS mutation and the Ki-67 index were determined. A meta-analysis was conducted by a systematic search of PubMed, Web of Science, and CNKI databases, and the data from published articles were combined with that of our study. The association of the SUVmax with KRAS mutation and the Ki-67 index was determined using the odds ratio to estimate the pooled results. The hazard ratio was used to quantitatively evaluate the prognosis of the SUVmax in CRC. RESULTS: By analyzing the data of 66 patients with CRC, the SUVmax was found not to be related to the tumor-node-metastasis stage, clinical stage, sex, and KRAS mutation but was related to the tumor location and nerve invasion. The SUVmax had no significant correlation with the tumor biomarkers and the Ki-67 index. Data of 17 studies indicated that the SUVmax was significantly increased in the mutated type compared with the wild type of KRAS in CRC; four studies showed that there was no remarkable difference between patients with a high and low Ki-67 index score regarding the SUVmax. Twelve studies revealed that the SUVmax had no significant association with overall survival and disease-free survival in CRC patients. CONCLUSIONS: Based on the combined data, this study demonstrated that the SUVmax of 18F-FDG PET/CT was different between colon and rectal cancers and associated with KRAS mutation but not the Ki-67 index; there was no significant association between the SUVmax and survival of patients with CRC.

Systematic Analysis of the Clinical Significance of Hyaluronan-Mediated Motility Receptor in Colorectal Cancer.

Background: The role of hyaluronan-mediated motility receptor (HMMR) in colorectal cancer (CRC) remains unclear. The present study aimed to explore the association of HMMR with the development and prognosis of CRC using sequence datasets, clinical tissues, blood samples, and cell lines. Methods: CRC datasets were downloaded from TCGA and GEO databases. Forty CRC tissue samples, 120 CRC blood samples, and 100 healthy controls were collected. Four CRC cell lines (HCT116, HT-29, LoVo, and SW480) and one normal human colon mucosal epithelial cell line (NCM460) were cultured. RT-qPCR was used to determine the expression of HMMR in the tissues and cell lines. ELISA was used to measure HMMR levels in the blood samples. Results: The expression of HMMR was significantly increased in CRC tissues than in corresponding adjacent tissues based on TCGA and GEO datasets, and clinical CRC tissues. No associations were found between the expression of HMMR and the TNM stage or other clinical parameters. The expression of HMMR varied in different CRC cell lines. The blood levels of HMMR tended to be higher in patients with CRC than in healthy controls. TCGA and GEO datasets showed inconsistent results regarding the association of HMMR expression with the survival of patients with CRC. Conclusion: The expression of HMMR is increased in CRC tissues but not in the blood. The expression of HMMR is independent of CRC development and has no prognostic significance in patients with CRC.

Construction of a long noncoding RNA-based competing endogenous RNA network and prognostic signatures of left- and right-side colon cancer.

BACKGROUND: Cancers located on the right and left sides of the colon have distinct clinical and molecular characteristics. This study aimed to explore the regulatory mechanisms of location-specific long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in colon cancer and identify potential prognostic biomarkers. METHOD: Differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between right- and left-side colon cancers were identified by comparing RNA sequencing profiles. Functional enrichment analysis was performed for the DEGs, and a ceRNA network was constructed. Associations between DELs and patient survival were examined, and a DEL-based signature was constructed to examine the prognostic value of these differences. Clinical colon cancer tissues and Gene Expression Omnibus (GEO) datasets were used to validate the results. RESULTS: We identified 376 DELs, 35 DEMs, and 805 DEGs between right- and left-side colon cancers. The functional enrichment analysis revealed the functions and pathway involvement of DEGs. A ceRNA network was constructed based on 95 DEL-DEM-DEG interactions. Three DELs (LINC01555, AC015712, and FZD10-AS1) were associated with the overall survival of patients with colon cancer, and a prognostic signature was established based on these three DELs. High risk scores for this signature indicated poor survival, suggesting that the signature has prognostic value for colon cancer. Examination of clinical colon cancer tissues and GEO dataset analysis confirmed the results. CONCLUSION: The ceRNA regulatory network suggests roles for location-specific lncRNAs in colon cancer and allowed the development of an lncRNA-based prognostic signature, which could be used to assess prognosis and determine treatment strategies in patients with colon cancer.

Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center.

BACKGROUND Natural killer (NK) cells are important for the prognosis of multiple cancers, but their prognostic value remains to be evaluated in patients with gastric cancer. Thus, this retrospective study was conducted at a single center to investigate the association between percentage of NK cells in the peripheral blood and prognosis in patients with gastric cancer. MATERIAL AND METHODS The data of 180 gastric cancer patients were collected. Univariate and multivariate Cox regression models were applied to screen candidate prognostic factors. A time-dependent receiver operating characteristic curve was employed to evaluate the ability of NK cells as a prognostic marker. Furthermore, we determined the correlation between the NK cells percentage and other parameters and their clinical significance. RESULTS Patients with a higher percentage of NK cells survived longer than those with a lower percentage of NK cells. Cox analysis revealed that NK cells could be used as an independent indicator for patients with gastric cancer. The percentage of NK cells was positively correlated with lymphocyte count and albumin, but was negatively correlated with CA125 and neutrophil-lymphocyte ratio. The area under the curve for NK cells in predicting the 5-year survival rate for gastric cancer was 0.792. This increased to 0.830 upon combining NK cells with neutrophil-lymphocyte ratio. Patients at early T, N, and clinical stages possessed a significantly higher percentage of NK cells compared to those at advanced T, N, and clinical stages of gastric cancer. CONCLUSIONS Our results suggest that a higher percentage of NK cells predicts is associated with longer survival of gastric cancer patients and could serve as an independent prognostic biomarker.

A Colon-Targeted Oral Probiotics Delivery System Using an Enzyme-Triggered Fuse-Like Microcapsule.

Probiotics are closely related to human health. However, it is hard to find an appropriate disintegration mode for encapsulation to balance the survival, release, and adhesion of probiotics simultaneously during the current colon-targeted oral delivery, which leads to limited colonization. In this study, an enzyme-triggered fuse-like microcapsule is constructed using alginate and protamine via the electrostatic droplet combined with the layer by layer self-assembly. The multilayer microcapsule can protect the probiotics in the stomach and disintegrate layer by layer under the catalysis of trypsin in the intestine. The formulation with two protamine layers showed the best protection for Escherichia coli MG1655 (EM) during the oral delivery; as well the minimal release at the gastric pH value but a burst release after 1 h at the intestinal pH value. In particular, the adhesion strength of EM is improved with the increase of the layer number. In vivo experiments demonstrate that the EM enters into the stationary phase within 12 h in the colon. Moreover, the blood biochemistry and histological analysis demonstrates the safety of the microcapsule formulation. It can be concluded that this microcapsule can help the probiotics survive during the delivery, then release and colonize in the colon.

Diagnostic and prognostic value of plasma heat shock protein 90alpha in gastric cancer.

BACKGROUND: The role of plasma heat shock protein 90alpha (Hsp90α) in gastric cancers remains unclear. This study aimed to clarify the diagnostic and prognostic value of plasma Hsp90α in gastric cancer. METHODS: Data regarding 976 gastric cancer, 50 gastric inflammatory diseases, and 100 healthy controls were collected. Plasma Hsp90α levels in gastric cancer were compared to those in controls. Its correlation with tumor biomarkers and immune cells was examined. The association of plasma Hsp90α with clinical features and the diagnostic and prognostic value in gastric cancer were also determined. RESULTS: Plasma Hsp90α levels were remarkably increased in gastric cancer, compared to those in gastric inflammatory diseases and healthy controls. Moreover, plasma Hsp90α was correlated with CEA, CA125, CA153, CA199, T cells, Th/Ts ratio, and B cells. Plasma Hsp90α was also associated with the metastasis stage. Multivariate logistic regression analysis revealed that Hsp90α, B cells, and T cells were significantly associated with gastric cancer. Plasma Hsp90α has a moderate diagnostic value, which increased when combined with B cell, T cells. Finally, plasma Hsp90α was not associated with the survival of gastric cancer patients. CONCLUSION: Plasma Hsp90α was elevated in gastric cancer and correlated with tumor biomarkers and immune cells. Plasma Hsp90α was associated with the metastasis stage and had moderate diagnostic performance but little prognostic value in gastric cancer.

Clinical Significance and Prognostic Value of miR-28-5p in Colon Cancer.

BACKGROUND: The association of miR-28-5p with colon cancer remains to be elucidated. This study aimed to determine the clinical significance and prognostic value of miR-28-5p in colon cancer. METHODS: We retrospectively analyzed the data of miR-28-5p in colon adenocarcinoma data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and the data was divided into cancer group and normal group, respectively. Forty colon cancer tissues and adjacent normal tissues were collected and tested by qRT-PCR methods. The difference of the miR-28-5p expression between colon cancer and normal tissues was compared. The clinical significance of miR-28-5p in colon cancer and the association with the survival were determined. The predictive value of miR-28-5p in clinical features was determined using receiver operating characteristic curve. The target genes of miR-28-5p were identified, and the functional of target genes was performed using bioinformatics analysis. RESULTS: : The expression of miR-28-5p was increased in colon cancer tissues compared with normal controls (p = 0.037). The expression of miR-28-5p was significantly increased in tissues with distant metastases compared with that without distant metastases (p = 0.026). Patients with high expression of miR-28-5p have a shorter survival time than those with low expression (p = 0.004). Cox analysis showed that miR-28-5p was an independent predictor for the survival of patients (p = 0.014). Combination of miR-28-5p with TNM stage and clinical stage can improve the prognostic value for the patients (p < 0.05). miR-28-5p has a moderate predictive value in predicting the TNM stage and clinical stage (T stage: AUC = 0.515; N stage: AUC = 0.523, M stage: AUC = 0.572; clinical stage: AUC = 0.539). 711 potential target genes of miR-28-5p were screened; their function and pathways were identified. CONCLUSIONS: : This study demonstrated that miR-28-5p was increased in colon cancer and can be an independent indicator for the overall survival in patients with colon cancer.

Prognostic value of peripheral blood natural killer cells in colorectal cancer.

BACKGROUND: The association between natural killer (NK) cells and survival in colorectal cancer (CRC) patients remains controversial. This study aimed to clarify the prognostic value of peripheral blood NK cells in CRC patients. METHODS: A total of 447 CRC patients who underwent radical surgery and chemotherapy were retrospectively analyzed. Cox regression analyses were used to identify independent prognostic indicators. Correlation between NK cell percentage and other clinicopathological features (gender, age, histological grade, tumor stage, immune cells, and inflammatory indicators) was analyzed. The prognostic values of the combinations of NK cell percentage and other clinicopathological features were also determined. RESULTS: Multivariate Cox regression analysis revealed that NK cell percentage in the peripheral blood was an independent prognostic indicator in CRC patients. A higher percentage of NK cells indicated a longer survival time than a lower percentage. NK cell percentage was positively correlated to the T and B lymphocyte counts and negatively correlated to the patients' age and albumin levels. With an area of 0.741 under a receiver operating characteristic curve, NK cells have a moderate predictive value for 3rd-year survival in CRC. This area increased to 0.851 by combining NK cell percentage with the B lymphocyte count. Elderly patients and those at an advanced clinical stage presented a lower percentage of NK cells than younger patients and those at an early clinical stage. CONCLUSIONS: This study demonstrated that NK cells in the blood were an independent predictor of survival in CRC patients, and the combined count of NK cells and B lymphocytes could increase the prognostic value.

Genome-wide analysis to identify a novel distant metastasis-related gene signature predicting survival in patients with gastric cancer.

This study designed to identify a potential novel distant metastasis-related gene (DMGs) signature that predicting prognosis in patients with gastric cancer. DMGs was screened by overlapping the differentially expressed genes between M0 and M1 stage, and between tumor and adjacent normal tissue of gastric cancer by analyzing The Cancer Genome Atlas (TCGA) dataset. There were 83 DMGs were identified, the integrative analysis revealed these DMGs were involved in several biological process and pathway. A six-DMGs prognostic signature was developed based on the risk score obtained from Cox analysis. Patients with low risk score presented significantly shorter survival time. This prognostic signature has a moderate predictive value for the overall survival in gastric cancer patients, with an area under curve of 0.604. The DMGs prognostic signature also significantly associated with the overall survival of gastric cancer patients, and showed a better performance for predicting prognosis than traditional clinical indicators. The joint effect of risk score with clinical features could remarkably increased the predictive value as compared with single variable. The results from 60 gastric cancer tissues verified the prognostic value of the six-DMGs prognostic signature. In conclusions, the present study identified a novel six-DMGs prognostic signature that could serve as a biomarker for the prognosis prediction of patients with gastric cancer.

The association and diagnostic value of red blood cell distribution width in colorectal cancer.

Red blood cell distribution width (RDW) is associated with several diseases. However, the diagnostic value of RDW and its related factors remain unclear in colorectal cancer (CRC).This single-center retrospective study evaluated 211 Chinese CRC patients and 103 healthy controls. The association of RDW with the clinical parameters of CRC, as well as its correlations with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were analyzed. The diagnostic value of RDW alone or combined with CEA and CA19-9 was evaluated using receiver operating characteristic curve analysis. A meta-analysis was also performed to combine our data with previously published data to enhance our findings.In the CRC patients, RDW was clearly elevated and was significantly associated with CRC tumor location, histological type, T status (but not N or M status), and clinical stage. However, RDW was not significantly correlated with CEA or CA19-9 levels. Using RDW to diagnose CRC provided a sensitivity of 53.1% and specificity of 77.7%. The diagnostic accuracy of RDW was enhanced by combining RDW with CEA and CA19-9 levels. We identified 5 previous studies with 633 CRC patients and 1050 controls, which were combined with our cases and controls. The meta-analysis revealed an overall sensitivity of 69%, specificity of 70%, and an area under the curve of 0.74.In CRC cases, RDW was associated with tumor location, histological type, T status, and clinical stage. Furthermore, RDW had a moderate value for diagnosing CRC and might be useful in this setting.

Association and diagnostic value of serum SPINK4 in colorectal cancer.

The role of serum serine peptidase inhibitor, Kazal type 4 (SPINK4), in colorectal cancer (CRC) is largely unknown. This study aimed to explore the association and diagnostic value of serum SPINK4 in CRC. A total of 70 preoperative CRC patients, 30 postoperative CRC patients, 30 gastric cancer patients, and 30 healthy controls were enrolled. Using enzyme-linked immunosorbent assays, we found that the serum SPINK4 level was significantly increased in preoperative CRC compared with postoperative CRC patients, gastric cancer patients, and healthy controls (p < 0.05). The serum SPINK4 level was remarkably elevated in colon cancer compared with rectal cancer and was enhanced in the M1 stage compared with the M0 stage (p < 0.05). The area under the receiver operating characteristic curve of serum SPINK4 level in the diagnosis of CRC was 0.9186, with a sensitivity and specificity of 0.886 and 0.900, respectively, and a cut-off value of 2.065. There was no significant difference between high and low expression of serum SPINK4 regarding the overall survival time and disease-free survival (p > 0.05). This study demonstrated that the serum SPINK4 level increased in CRC and was associated with the location and distant metastasis of CRC. It had a high diagnostic value in CRC but was not associated with the survival of CRC patients.

Impact of primary colorectal Cancer location on the KRAS status and its prognostic value.

BACKGROUND: Colorectal cancer (CRC) originating from the right-sided or left-sided colon is distinct clinicopathological entity. The KRAS status and its prognostic value in CRC remain controversial. This study aimed to investigate the association of KRAS status with clinicopathological features and prognostic value in CRC. METHODS: 178 colon cancer and 145 rectal cancer patients were enrolled. KRAS mutation test was performed on paraffin-embedded tumor samples using PCR methods. The colon cancer was divided into right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Studies that reported the association of KRAS mutation with CRC clinical features and prognosis in databases were searched prior to 2018. The data of the present study was combined with the data of published studies using meta-analysis methods. RESULTS: No significant difference between colon cancer and rectal cancer regarding the KRAS status. The KRAS mutation was much frequent in RCC than in LCC (p = 0.010). 17 studies with 11,385 colon cancer patients were selected, the pooled results of our data and previous published data showed that KRAS mutation was more frequent in RCC compared with in LCC (p < 0.01); KRAS mutation was not associated with the prognosis in RCC patient; however, KRAS mutation indicated a poor prognosis in LCC patients compared with KRAS wild type (p < 0.01). CONCLUSION: KRAS status has no difference between colon cancer and rectal cancer. KRAS mutation was more frequent in RCC than in LCC, and associated with a poor prognosis in LCC patients, but not in RCC patients.