BackgroundImmune-related genes (IRGs) play important roles in the tumor immune microenvironment and can affect the prognosis of cancer. This study aimed to construct a novel IRG signature for prognostic evaluation of stage II colorectal cancer (CRC).MethodsGene expression profiles and clinical data for stage II CRC patients were collected from the Cancer Genome Atlas and Gene Expression Omnibus database. Univariate, multivariate Cox regression, and least absolute shrinkage and selection operator regression were used to develop the IRG signature, namely IRGCRCII. A nomogram was constructed, and the “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) method was used to estimate immune cell infiltration. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in 30 pairs of primary stage II CRC and matched normal tissues.ResultsA total of 466 patients with stage II CRC were included, and 274 differentially expressed IRGs were identified. Six differentially expressed IRGs were detected and used to construct the IRGCRCII signature, which could significantly stratify patients into high-risk and low-risk groups in terms of disease-free survival in three cohorts: training, test, and external validation (GSE39582). Receiver operating characteristics analysis revealed that the area under the curves of the IRGCRCII signature were significantly greater than those of the OncotypeDX colon signature at 1 (0.759 vs. 0.623), 3 (0.875 vs. 0.629), and 5 years (0.906 vs. 0.698) disease-free survival, respectively. The nomogram performed well in the concordance index (0.779) and calibration curves. The high-risk group had a significantly higher percentage of infiltrated immune cells (e.g., M2 macrophages, plasma cells, resting mast cells) than the low-risk group. Finally, the results of qRT-PCR and immunohistochemistry experiments performed on 30 pairs of clinical specimens were consistent with bioinformatics analysis.ConclusionThis study developed and validated a novel immune prognostic signature based on six differentially expressed IRGs for predicting disease-free survival and immune status in patients with stage II CRC, which may reflect immune dysregulation in the tumor immune microenvironment.

Background: Recently, a study from our center indicated that the ratio of preoperative carcinoembryonic antigen (CEA) concentration to maximum tumor diameter (DMAX) may be a prognostic marker for patients with rectal cancer. Therefore, the study aimed to evaluate whether this ratio (CEA/DMAX) has prognostic value for patients with stage II colorectal cancer (CRC). Methods: A prospectively maintained database was searched for patients with pathologically confirmed stage II CRC who underwent surgery between January 2010 and March 2019. Patients were stratified according to the mean CEA/DMAX value into low and high CEA/DMAX groups. Kaplan-Meier, univariable, and multivariable Cox regression analyses were used to evaluate whether the CEA/DMAX could predict overall survival (OS) and disease-free survival (DFS). Nomograms were constructed in terms of the results of multivariable Cox regression analyses. Results: The study included 2,499 patients with stage II CRC. The mean CEA/DMAX value was 2.33 (ng/mL per cm). Kaplan-Meier analyses revealed that, relative to the low CEA/DMAX group, the high CEA/DMAX group had significantly poorer OS (67.31% vs. 85.02%, P<0.001) and DFS (61.41% vs. 77.10%, P<0.001). The multivariable Cox regression analysis revealed that CEA/DMAX independently predicted OS (hazard ratio: 2.58, 95% confidence interval: 1.51-4.38, P<0.001) and DFS (hazard ratio: 1.97, 95% confidence interval: 1.38-2.83, P<0.001). Two simple-to-use nomograms comprising CEA/DMAX, age, T stage, and lymphovascular invasion were developed to predict 1-, 3-, and 5-year rates of OS and DFS among patients with stage II CRC. The nomograms had good performance based on the concordance index, receiver operating characteristic (ROC) curve analysis, and calibration curves. Subgroup analyses further confirmed that a high CEA/DMAX was associated with poor OS and DFS among patients with stage II colon cancer and among patients with stage II rectal cancer (both P<0.05).Conclusions: Among patients with stage II CRC, a high CEA/DMAX independently predicted poor OS and DFS, and the predictive abilities were also observed in subgroup analyses of patients with stage II colon cancer or rectal cancer. Furthermore, we developed two nomograms that had good accuracy for predicting the prognosis of stage II CRC.

Background Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poorer prognosis in several human malignancies, but their significance in gastric cancer (GC) remains to be clearly defined. Our study aimed to investigate the prognostic value of LVI/PNI in patients with curative resected GC. Methods Records of 1488 patients with stage I‐–III GC and 3327 patients with stage I–III colorectal cancer (CRC) were reviewed retrospectively, and difference in the incidence of LVI/PNI between GC and CRC was compared. Univariate and multivariate analyses were used to evaluate whether LVI/PNI was an independent risk factor for lymph node metastasis (LNM) and overall survival (OS) in GC. Results Patients with stage I–III GC had a significantly higher incidence of LVI/PNI than patients with stage I–III CRC (50.54% vs. 21.91%, p < 0.001). LVI/PNI was significantly associated with higher CEA, higher CA199, deeper tumor invasion, more lymph node metastasis, and advanced TNM stage in GC ( p < 0.05). Multivariate logistic regression analysis identified LVI/PNI (OR = 2.64, 95%CI: 2.05–3.40, p < 0.001) as an independent risk factor for LNM in GC. The OS rate was significantly lower in the LVI/PNI‐positive GC group than that in the LVI/PNI‐negative GC group ( p < 0.001). On multivariate Cox regression analysis, LVI/PNI (HR = 1.34, 95%CI: 1.04–1.71, p = 0.023) was an independent prognostic factor for OS in GC. Conclusion GC has a high incidence of LVI/PNI, which was closely associated with disease progression. LVI/PNI could serve as an independent risk factor for LNM and the prognosis of patients with curative resected GC. These findings will be helpful in predicting survival outcomes more accurately and establishing individualized treatment plans.

Background The clinical characteristics of synchronous colorectal cancer (SCRC) reported in previous studies differ significantly. Furthermore, little is known about the characteristics of early-onset synchronous colorectal cancer (EO-SCRC). The aim of this retrospective study was to identify the clinicopathological characteristics of SCRC and EO-SCRC and define their relevant prognostic factors. Methods Patients who underwent surgery for SCRC and primary unifocal colorectal cancer (PCRC) between January 2007 and December 2020 were included in this study. The clinical, histological, and molecular characteristics of the patient’s tumours were analysed. The primary endpoint was overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess the association between clinicopathological factors and patient survival. Results A total of 1554 patients were included in the analysis. Of these, 1132 (72.84%) had PCRC and 422 (27.16%) had SCRC. SCRC occurred more frequently in the elderly (P < 0.001) and in male patients (P = 0.002). The 5-year OS rate was 73.7% ± 2.0% for PCRC and 61.9% ± 3.9% for SCRC (P < 0.05). However, the Cox regression analysis showed that SCRC was not an independent prognostic factor for the prediction of OS. A total of 64 patients (15.17%) in the SCRC group had early-onset colorectal cancer (EOCRC), whereas 257 (22.70%) in the PCRC group had EOCRC (P = 0.001). The proportion of patients with deficient mismatch repair proteins (dMMR) in EO-SCRC subgroup was significantly higher than that in late-onset synchronous colorectal cancer (LO-SCRC) subgroup (23.44% vs. 10.34%, P = 0.006). Patients with EO-SCRC had more TNM stage IV (P < 0.001) and fewer opportunities for radical surgery (79.69% vs. 92.22%, P = 0.007) than those with early-onset primary unifocal colorectal cancer (EO-PCRC). There was no significant difference in 5-year OS between the EO-SCRC and LO-SCRC subgroups (P = 0.091) and between the EO-SCRC and EO-PCRC subgroups (P = 0.094). Multivariate analysis revealed that EOCRC was an independent good prognostic parameter for colorectal cancer (CRC) and SCRC. Conclusion For patients with operative treatment, EO-SCRC is different from LO-SCRC and EO-PCRC. Patients with SCRC show a poorer survival rate than those with PCRC. However, SCRC is not an independent prognostic factor for CRC, whereas EOCRC is a good prognostic factor for CRC and SCRC.

BackgroundLymph node metastasis (LNM) is a critical factor in determining the prognosis of gastric cancer (GC), but its underlying mechanism remains unclear. The tumor mutational burden (TMB) has recently been recognized as a biomarker for predicting prognosis and response to immune checkpoint inhibitors, while mucin 16, cell surface associated (MUC16) is frequently mutated in GC. This study explored whether MUC16 mutation status is associated with TMB, LNM, and prognosis in patients with GC.MethodsSomatic mutation data were downloaded from three GC cohorts. TMB values were calculated and associations between the TMB and clinical characteristics were analyzed. The mutational landscapes of these three GC cohorts were individually explored and visualized using waterfall diagrams. Univariate logistic regression and Kaplan-Meier survival analysis were performed to screen for mutated genes associated with LNM and overall survival (OS). Associations between MUC16 mutations and TMB, microsatellite instability (MSI), LNM, and tumor microenvironment signatures were explored.ResultsTMB was associated with LNM and OS in patients with GC. Analyzing the three GC cohorts (The Cancer Genome Atlas-Stomach Adenocarcinoma, International Cancer Genome Consortium [ICGC]-China, and ICGC-Japan) revealed that MUC16 was one of the most frequently mutated genes in patients with GC. MUC16 mutations were associated with better prognosis, including lower LNM rates and improved OS rates. In addition, MUC16 mutation status was associated with TMB and MSI statuses. Fifteen upregulated and 222 downregulated genes were identified in patients with MUC16 mutations, compared to in those in patients with wild-type MUC16. An altered tumor microenvironment signature was also identified in GC samples with MUC16 mutations; it was characterized by significantly decreased infiltration regarding stromal cells, CD4+ T cells, and macrophages.ConclusionMUC16 mutation status was associated with TMB, microsatellite status, LNM, and survival in patients with GC. These findings may provide new insights into the mechanism of LNM and could act as a signpost for prognostic predictions and immunotherapy guidance for patients with GC.