Shiyong Huang

Background: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the predominant serum tumour markers (STMs) for predicting the prognosis of colorectal cancer (CRC). The objective of this research is to develop clinical prediction models based on preoperative and postoperative CEA and CA19-9 levels.Methods: 1,452 consecutive participants with stage I-III colorectal cancer were included. Kaplan-Meier method, log-rank test, and multivariate COX regression were used to evaluate the significance of preoperative and postoperative STMs. Patients were grouped into a discovery cohort (70%) and a validation cohort (30%). Variables for the nomograms were selected according to the Akaike information criterion (AIC). Subsequently, two clinical predictive models were constructed, evaluated, validated, and then compared with the AJCC 8th TNM stage.Results: The overall survival (OS) rate and disease-free survival(DFS) rate declined progressively as the number of positive tumour markers(NPTMs) before and after surgery increased. For both OS and DFS, age, sex, pN stage, and NPTMs before and after surgery were independent prognostic factors, and then clinical prediction models were developed. The Concordance index (C-index), Receiver operating characteristic (ROC) curve, calibration curve, Decision curve analysis (DCA), and risk score stratification all indicated that the models possessed robust predictive efficacy and clinical applicability. The Net reclassification index (NRI) and Integrated discrimination improvement (IDI) indicated that the performance of models was significantly superior to the TNM stage.Conclusion: Nomograms based on pre-and postoperative CEA and CA19-9 can accurately predict survival and recurrence for stage I-III CRC patients after radical surgery, and were significantly better than the AJCC 8th TNM stage.

Background: Pachymic acid (PA), a purified triterpene extracted from the medicinal fungus Poria cocos, is known for its antiemetic, anti-inflammatory, and antitumor properties. However, the effect of PA on colorectal cancer and its underlying mechanism are yet to be elucidated. In this study, we delved into the chemotherapeutic effects and underlying mechanisms of PA on colorectal cancer. Methods: The impact of PA on the proliferation of cells in colon cancer was investigated employing the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU). Moreover, its role in the migration of colon cancer cells was assessed using the transwell assay. Bioinformatic analysis was performed to predict interferon alpha-inducible protein 6 (IFI6) binding miRNA and dual luciferase assay was used to validate this interaction. The IFI6-overexpressing cell lines were established and used to evaluate if PA regulates IFI6 to affect a serine/threonine protein kinase (AKT) and SMAD Family Member 3 (Smad 3) signaling pathways by western blot between control, PA + Vector and PA + IFI6-overexpression (OE) groups. Furthermore, miR-148a-5p inhibitor was applied to investigate the effect of PA on colorectal cancer cells. Results: PA showed antitumor effects in vitro by inhibiting colon cancer cell proliferation and metastasis in HT29 and DLD-1 cells (p < 0.01). Mechanistically, our data suggested that PA decreased colon cancer cell proliferation and metastasis by increasing miR-148a-5p expression to repress the levels of IFI6, AKT, and Smad 3 signaling pathways (p < 0.05). Moreover, overexpression of IFI6 and administration of miR-148a-5p inhibitors reversed the inhibitory effects of PA on the AKT and Smad-3 pathways (p < 0.01), indicating a critical role for IFI6 in colorectal cancer progression. Conclusion: Our study indicates PA as a potential therapeutic candidate for colorectal cancer growth and metastasis. This study provides a foundation for the potential application of PA in colorectal cancer therapy.

We aimed to develop a clinical predictive model for predicting the overall survival (OS) in stage I–III CRC patients after radical resection with normal preoperative CEA. This study included 1082 consecutive patients. They were further divided into a training set (70%) and a validation set (30%). The selection of variables for the model was informed by the Akaike information criterion. After that, the clinical predictive model was constructed, evaluated, and validated. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were employed to compare the models. Age, histologic type, pT stage, pN stage, carbohydrate antigen 242 (CA242), and carbohydrate antigen 125 (CA125) were selected to establish a clinical prediction model for OS. The concordance index (C-index) (0.748 for the training set and 0.702 for the validation set) indicated that the nomogram had good discrimination ability. The decision curve analysis highlighted that the model has superior efficiency in clinical decision-making. NRI and IDI showed that the established nomogram markedly outperformed the TNM stage. The new clinical prediction model was notably superior to the AJCC 8th TNM stage, and it can be used to accurately assess the OS of stage I–III CRC patients undergoing radical resection with normal preoperative CEA.

With the emergence of novel variants, there have been widespread COVID-19 infections in the Chinese mainland recently. Compared to ancestral COVID-19 variants, Omicron variants become more infectious, but less virulent. Previous studies have recommended postponing non-emergency surgery for at least 4–8 weeks after COVID-19 infection. However, delayed surgery has been shown to be associated with tumor progression and worse overall survival for cancer patients. Here, we examined surgery risk and optimal timing for colorectal cancer patients with perioperative COVID-19 infection. A total of 211 patients who underwent colorectal cancer surgery from 1 October 2022 to 20 January 2023 at Xinhua Hospital were included. In addition, COVID-19-infected patients were further categorized into three groups based on infected time (early post-COVID-19 group, late post-COVID-19 group and postoperative COVID-19 group). The complication rate in patients with COVID-19 infection was 26.3%, which was significantly higher than in control patients (8.4%). The most common complications in COVID-19-infected patients were pneumonia, ileus and sepsis. Patients who underwent surgery close to the time of infection had increased surgery risks, whereas surgery performed over 1 week after recovery from COVID-19 did not increase the risk of postoperative complications. In conclusion, surgery performed during or near the time of COVID-19 infection is associated with an increased risk of developing postoperative complications. We recommend that the safe period for patients with recent COVID-19 infection in colorectal cancer surgery be at least 1 week after recovery from COVID-19.

Colorectal cancer (CRC) is the most prevalent type of malignant tumor of the gastrointestinal tract. In the current study, we characterized the landscape of genomic alterations in CRC patients. Based on the results of whole-exome sequencing (WES), we identified 31 significantly mutated genes. Among them, several genes including TP53, KRAS, APC, PI3KCA, and BRAF were reported as significantly mutated genes in previous studies. In the current study, the most frequently mutated gene was TP53, which encodes tumor suppressor p53, affecting approximately 60 of CRC patients. In addition, we performed the expression profiles of significantly mutated genes between the normal group and tumor groups and identified 20 differentially expressed genes (DEGs); among them, CSMD3, DCHS2, LRP2, RYR2, and ZFHX4 were significantly negatively correlated with PFS. Moreover, consensus clustering analysis for CRC based on the expression of significantly somatic mutated genes was performed. In total, three subtypes of CRC were identified in CRC, including cluster1 (n=453), cluster2 (n=158), and cluster 3 (n=9), based on expression level of significantly somatic mutated genes. Clinicopathological features analysis showed subtype C1 had the longest progression-free survival (PFS) with median time of 8.2 years, while subtypes C2 and C3 had 4.1 and 2.7 years of PFS, respectively. Moreover, we found three subtypes related to tumor infiltration depth, lymph node metastasis, and distant metastasis. Immune infiltration analysis showed the tumor infiltration levels of B cell native, T cell CD8+, T cell CD4+ memory activated, T cell gamma delta, NK cell resting, macrophage M0, macrophage M2, myeloid dendritic cell activated, mast cell activated, and mast cell resting significantly changed among the three groups, demonstrating the three subgroups classified by 22 somatically significantly mutated genes had a high capacity to differentiate patients with different immune statuses, which is helpful for the prediction of immunotherapy response of CRC patients. Our findings could provide novel potential predictive indicators for CRC prognosis and therapy targets for CRC immunotherapy.

Early research shows that disrupting the circadian rhythm increases the risk of various cancers. However, the roles of circadian clock genes in colorectal cancer, which is becoming more common and lethal in China, remained to be unclear. In conclusion, the present study has demonstrated that multiple CCGs were dysregulated and frequently mutated in CRC samples by analyzing the TCGA database. The higher expression levels of REV1, ADCYAP1, CSNK1D, NR1D1, CSNK1E, and CRY2 had a strong link with shorter DFS time in CRC patients, demonstrating that CCGs had an important regulatory role in CRC development. Moreover, 513 CRC tumor samples were divided into 3 categories, namely, cluster1 ( ), cluster2 ( ), and cluster 3 ( ), based on the expression levels of the CCGs. Clinical significance analysis showed that the overall survival and disease-free survival of cluster 2 and cluster 3 were significantly shorter than those of cluster 1. The stemness scores in cluster 1 and cluster 2 were significantly higher than those of cluster 3 CRC samples. Clinically, we found that the C3 subtype had significantly higher percentage of T3/T4, N1/N2, and grades III and IV than groups C1 or C2. In addition, we reported that different CRC clusters had significantly different tumor-infiltrating immune cell signatures. Finally, pancancer analysis showed that higher expression of CSNK1D was correlated with shorter DFS time in multiple cancer types, such as COAD and LIHC, and was dysregulated in various cancers. In conclusion, we effectively developed a CCG-related predictive model and opened up new avenues for research into immune regulatory mechanisms and the development of immunotherapy for CRC.

Secreted frizzled-related protein 1 (SFRP1) is a member of the SFRPs family that modulates the Wnt signal transduction pathway. Recent studies have showed down-regulation of SFRP1 expression in colorectal cancer (CRC). We aimed to evaluate the effect of SFRP1 on the proliferation, migration, invasion and apoptosis of CRC cells in vitro. We used real-time fluorescence quantification (RT-PCR) and Western blotting to detect SFRP1 expression in CRC, pericarcinomatous tissues and CRC cell lines. We assessed the influence of overexpression and knockdown of SFRP1 on CRC cell proliferation, migration, invasion, and apoptosis, Western blotting was used to evaluate protein levels of Wnt, β-catenin, and apoptosis-related proteins. The expression of SFRP1 was significantly decreased in CRC tissues. Among the six CRC cell lines (sw-480, sw1116, caco-2, ht-29, colo-205, and hct-116), RT-PCR revealed that sw1116 cells had the lowest expression of SFRP1, while caco-2 cells had the highest SFRP1 expression. SFRP1 overexpression in sw1116 cells significantly suppressed cell proliferation while SFRP1 knockdown in caco-2 cells significantly increase the cell proliferation. In addition, overexpression of SFRP1 in sw1116 cells remarkedly suppressed cell migration and invasion, whereas knockdown of SFRP1 in caco-2 cells resulted in significant enhancement of migration and invasion. Furthermore, SFRP1 overexpression in sw1116 cells promoted cell apoptosis. Western blotting showed that SFRP1 overexpression significantly decreased the protein levels of Wnt, β-catenin and apoptosis-related proteins, including MMP2, MMP9, Twist, CDK1, TGF, and Bcl2. Our results demonstrate that SFRP1 suppresses cell proliferation, migration and invasion, and promotes apoptosis in CRC cells.