Reliable evaluation methods serve an important role in improving the prognosis of patients with colorectal cancer (CRC), guiding the development of treatment plans and prolonging patient survival. In the present study, several preoperative inflammatory indicators and tumor markers were evaluated for their ability to predict CRC prognosis. A total of 224 eligible patients with CRC were enrolled and divided into the training (n=150) and validation (n=74) groups. The training group underwent both Least Absolute Shrinkage and Selection Operator (LASSO) regression and Cox regression analyses to discern pivotal prognostic factors, to formulate a nomogram for overall survival prediction. The results showed that LASSO regression, along with univariate and multivariate Cox regression analyses, identified neutrophil-lymphocyte ratio (NLR), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) as effective risk factors for CRC. The concordance index of the nomogram was 0.716 in the training group and 0.700 in the validation group. The areas under the curve for predicting 3-year survival were 0.748 and 0.776 in the training and validation groups, respectively, and for 5-year survival were 0.749 and 0.731, respectively. In conclusion, NLR, CA19-9 and CEA may serve as effective additions to traditional clinical assessment methods and a nomogram incorporating these three preoperative indicators could be used efficiently to predict the prognosis of patients with CRC.

Background Hematological metastasis has been recognized as a crucial factor contributing to the high rates of metastasis and mortality observed in colorectal cancer (CRC). Notably, exosomes derived from cancer cells participate in the formation of CRC pre-metastatic niches; however, the mechanisms underlying their effects are largely unknown. While our preliminary research revealed the role of exosome-derived disintegrin and metalloproteinase 17 (ADAM17) in the early stages of CRC metastasis, the role of exosomal ADAM17 in CRC hematogenous metastasis remains unclear. Methods In the present study, we isolated and purified exosomes using ultracentrifugation and identified exosomal proteins through quantitative mass spectrometry. In vitro, co-culture assays were conducted to evaluate the impact of exosomal ADAM17 on the permeability of the blood vessel endothelium. Vascular endothelial cell resistance, the cell index, membrane protein separation, flow cytometry, and immunofluorescence were employed to investigate the mechanisms underlying exosomal ADAM17-induced vascular permeability. Additionally, a mouse model was established to elucidate the role of exosomal ADAM17 in the modulation of blood vessel permeability and pre-metastatic niche formation in vivo. Results Our clinical data indicated that ADAM17 derived from the circulating exosomes of patients with CRC could serve as a blood-based biomarker for predicting metastasis. The CRC-derived exosomal ADAM17 targeted vascular endothelial cells, thus enhancing vascular permeability by influencing vascular endothelial cadherin cell membrane localization. Moreover, exosomal ADAM17 mediated the formation of a pre-metastatic niche in nude mice by inducing vascular leakage, thereby promoting CRC metastasis. Nonetheless, ADAM17 selective inhibitors effectively reduced CRC metastasis in vivo. Conclusions Our results suggest that exosomal ADAM17 plays a pivotal role in the hematogenous metastasis of CRC. Thus, this protein may serve as a valuable blood-based biomarker and potential drug target for CRC metastasis intervention.

Replication factor C 5 (RFC5) is involved in a variety of biological functions of cancer. However, the expression pattern of RFC5 and the underlying mechanisms in colorectal cancer (CRC) remain elusive. Here, we show that RFC5 is significantly upregulated in CRC tissues and cells. Patients with CRC and increased RFC5 levels have an unfavorable prognosis. RFC5 can promote the proliferation, migration, and invasion of CRC cells and inhibit the apoptosis of CRC cells. Additionally, upstream of RFC5, we constructed the competing endogenous RNA network and confirmed that RFC5 in this network was inhibited by miR‐3614‐5p by directly targeting its 3′‐untranslated regions. We verified that circ_0038985, which is positively correlated with RFC5, directly targeted miR‐3614‐5p. Overexpression of circ_0038985 promoted CRC cell migration and invasion, and these effects were partially reversed by the reintroduction of miR‐3614‐5p. Moreover, we found that RFC5 may promote the vascular endothelial growth factor A (VEGFa)/vascular endothelial growth factor receptor 2 (VEGFR2)/extracellular signal‐regulated protein kinase (ERK) pathway. The knockdown of RFC5 reduced CRC tumorigenesis in vivo. Collectively, these data demonstrate that the circ_0038985/miR‐3614‐5p/RFC5 axis plays a critical role in the progression of CRC, and RFC5 may promote CRC progression by affecting the VEGFa/VEGFR2/ERK pathway.

Abstract Background: Reliable evaluation methods play an important role in improving the prognosis of colorectal cancer patients, guiding the development of treatment plans, and prolonging patient survival. Several preoperative inflammatory indicators and tumor markers were evaluated in this study for predicting colorectal cancer (CRC) prognosis. Methods: A total of 224 eligible patients with CRC were enrolled in the present study. Patients were divided into a training group (n=150) and a validation group (n=74). The training cohort underwent both the least absolute shrinkage and selection operator (LASSO) regression and Cox regression analyses to discern pivotal prognostic factors, aiming to formulate a nomogram for the prediction of overall survival (OS). Results: LASSO regression, univariate and multivariate Cox regression analysis revealed that Neutrophil-lymphocyte ratio (NLR), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were effective risk factors. The concordance index (C-index) of the nomogram in the training and validation groups were 0.716 and 0.7 respectively. The areas under curve (AUC) of the nomogram for 3-years were 0.748 and 0.776, for 5-years were 0.749 and 0.773 respectively. Conclusion: NLR, CA199 and CEA were effective supplements to traditional clinical assessment methods. The nomogram incorporating the three preoperative indicators can be effectively and efficiently used to predict the prognosis of CRC patients.

Background:In recent years, reports regarding stimulator of interferon genes (STING) and the progression of colorectal cancer (CRC) have emerged rapidly, yet their association remains controversial. This research was aimed to provide an insight into the prognostic biomarker and therapeutic target significance of STING in CRC.Methods:CRC Cell lines of HCT116 and SW480, as well as 32 paired CRC specimens were chosen for this study. STING expressions were examined by immunohistochemistry to evaluate the correlation with clinicopathological factors. Data analysis of STING expressions in colon cancer and rectal cancer were performed using The Cancer Genome Atlas (TCGA) database. siRNA was transfected into cell lines for knocking down the expression of STING. Transwell assay was employed to evaluate cell migration and invasiveness. CCK-8 assay was used for assessing the change of cell proliferation. Drug sensitive test was involved to evaluate drug resistance of cell lines. Gene Set Enrichment Analysis (GSEA) was applied for exploring potential downstream mechanism of STING in CRC progression and Western blotting is used for mechanism validation.Results:In the thirty-two paired CRC and adjacent normal tissues, we found a significant up-regulated in STING expression with immunohistochemical staining in cancer tissues compared with adjacent normal tissues (P<0.01), which was correlated with the tumor-node-metastasis (TNM) stage of patients (P=0.028). Meanwhile, GESA enrichment analysis indicated a remarkable change in mTOR signaling following STING regulation. In HCT116 and SW480 cell lines of CRC, When STING was down-regulated, its biological behavior of cell viability, cell invasion and drug sensitivity to 5-fluorouracil were significantly reduced (P<0.05), we also observed the up-regulation of P-AMPK (P<0.05) and down-regulation of p-mTOR (P<0.05).Conclusions:STING expressions was significantly up-regulated in CRC tissues. Expression of STING was correlated with the TNM stage of patients. STING is found to promote cell proliferation, invasion ability and drug resistance mediating AMPK-mTOR signaling in CRC. STING could be a promising target for the sensitization of chemotherapy and inhibits CRC progression.

Abstract Background: Despite a rapidly growing body of pertinent literature, the relationship between stimulator of interferon genes (STING) protein expression and the progression of colorectal cancer (CRC) remains controversial. This study aimed to investigate the potential roles of STING as a prognostic biomarker and therapeutic target in the medical management of CRC. Methods: STING expression was examined by immunohistochemistry to evaluate its association with clinicopathological factors. Moreover, the effects of STING on CRC cell proliferation, migration, invasiveness, and drug resistance were examined. Gene set enrichment analysis was applied to explore potential downstream mechanisms of STING in CRC. Meanwhile, we evaluated the effect of STING on glucose uptake. Results: Our study confirmed that STING expression was significantly up-regulated in CRC tissues, and was associated with TNM stage and a poor prognosis. Additionally, STING promoted cell proliferation, migration, invasiveness, and drug resistance by mediating AMPK-mTOR signaling. Finally, we confirmed that STING regulates energy metabolism in CRC cells. Conclusions: STING may represent a promising prognostic biomarker and therapeutic target for chemosensitization and inhibition of CRC progression.