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Abstract Background KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. Methods 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. Results NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. Conclusions KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.

Abstract Purpose The overall survival (OS) of patients diagnosed with stage II‐III colorectal cancer (CRC) can vary greatly, even between patients with the same tumor stage. We aimed to design a nomogram to predict OS in resected, stage II‐III CRC and stratify patients with CRC into different risk groups. Patients and Methods Based on data from 873 patients with CRC, we used univariate Cox regression analysis to select the significant prognostic features, which were subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for feature selection. Cross‐validation was used to confirm suitable tuning parameters (λ) for LASSO logistic regression. Then, the nomogram was used to estimate 3‐ and 5‐year OS based on the multivariable Cox regression model. The survival curves of the two groups were produced using the Kaplan‐Meier method. Risk group stratification was performed to assess the predictive capacity of the nomogram. Results Preoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy were identified as independent prognostic factors by LASSO regression and integrated for the construction of the nomogram. The nomogram provided good discrimination, with C‐indices of 0.67 and 0.69 for the training and validation sets, respectively. Calibration plots illustrated excellent agreement between the nomogram predictions and actual observations for 3‐ and 5‐year OS. Moreover, a significant difference in OS was shown between patients stratified into different risk groups (P

Background: Inflammation and nutritional status are highly associated with colorectal cancer (CRC) prognosis. This study aimed to evaluate the prognostic value of the preoperative neutrophil-BMI ratio (NBR) in patients with CRC. Methods: A retrospective analysis was performed on 2471 patients with CRC who underwent surgical resection between 2004 and 2019. Patients were divided into two groups based on the cutoff value for NBR. Cox regression and Kaplan–Meier curves were used to evaluate overall survival (OS). Results: High NBR was associated with female sex, low BMI, colon, right-sided CRC, poor differentiation, T3 to 4 stage, M1 to 2 stage, high carcinoembryonic antigen (CEA) level, III-IV stage, microsatellite instability (MSI), and no adjuvant chemotherapy (all P

Background and Purpose: Systemic inflammation and nutritional status have been shown to be associated with the prognosis of colorectal cancer. The purpose of this study was to evaluate the impact of the serum C-reactive protein-to-body mass index ratio on the prognosis of patients with curatively resected colorectal cancer. Methods: We conducted a retrospective analysis of a database of 2,471 eligible patients with colorectal cancer who underwent curative resection at our hospital between 2004 and 2019. The optimal cut-off for CPR-to-BMI ratio was determined using maximally selected rank statistics. Patients were divided into 2 groups according to the cut-off value of the serum C-reactive protein-to-body mass index ratio. Kaplan-Meier curves and Cox regression analysis were used to compare overall survival. A two-sided P -value < 0.05 was considered statistically significant. Results: The proportion of patients with a high C-reactive protein-to-body mass index ratio increased with increasing age, male sex, right-sided colon cancer, poorly differentiated tumors, advanced-stage disease, local/distant metastases, tumor–node–metastasis stage, and microsatellite instability. In subgroup analysis according to tumor–node–metastasis stage, the overall survival of the high C-reactive protein-to-body mass index ratio group was significantly shorter than that of the low C-reactive protein-to-body mass index ratio group ( P < 0.001). Multivariate analysis identified age, differentiation, tumor–node–metastasis stage, carcinoembryonic antigen level, and the C-reactive protein-to-body mass index ratio as independent poor prognostic factors for overall survival. Conclusions: The C-reactive protein-to-body mass index ratio predicts the prognosis of patients with curatively resected colorectal cancer and is an independent risk factor for overall survival in patients with colorectal cancer.

Fluoropyrimidine-based chemotherapy is an essential component of systemic chemotherapy for colorectal cancer (CRC). The immune response is implicated in chemotherapy-induced cytotoxicity. Here, we reported an immune risk (Imm-R) model for prognostic prediction in patients receiving fluoropyrimidine-based chemotherapy. Gene expression profiles and corresponding clinical information were collected from four data sets and divided into training set (n = 183) and validation set (validation set1: n = 34; validation set2: n = 99). The composition of 22 tumor-infiltrating immune cells (TIICs) populations was characterized with the CIBERSORT deconvolution algorithm. A prognostic Imm-R model for predicting overall survival was established by performing least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis. T follicular helper cells and M0 macrophages were associated with better survival, while eosinophils were associated with worse survival. TIICs signature was constructed based on the above three immune cell types. Furthermore, a Imm-R model was created by integrating TIICs signature with immune-related genes (IRGs), which effectively in distinguishing CRC patients with poorer prognosis. The Imm-R model was associated with activation of the TGF-beta signaling and suppression of DNA damage. Results of this research provide new insights into the role of immunity for in fluoropyrimidine-based chemotherapy as well as a useful tools to predict the outcome of CRC patients receiving fluoropyrimidine-based chemotherapy.

Objective: Human epididymis protein 4 (HE4) has been approved for diagnosing ovarian cancer. The goal of this meta-analysis was to evaluate the clinical value of the serum HE4 in the diagnosis of ovarian cancer. Methods: The PubMed and Embase databases were searched to identify suitable studies. The sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) of HE4 for the diagnosis of ovarian cancer were commonly used as bivariates. Summary receiver operating characteristic curves were used to summarize overall test performances. Meta-Disc 1.4 software was used to analyze the data. Results: A total of 6,269 patients from 31 trials were subjected to meta-analysis. The summary estimates of HE4 for ovarian cancer diagnosis were as follows: SEN 0.73 (95% confidence interval [CI] 0.71-0.75); SPE 0.89 (95% CI 0.88-0.90); PLR 7.30 (95% CI 5.42-9.84); and NLR 0.15 (95% CI 0.10-0.23). SEN 0.74 (95% CI 0.72-0.76); SPE 0.89 (95% CI 0.88-0.90); PLR 7.35 (95% CI 5.55-9.73); NLR 0.14 (95% CI 0.09-0.21). Conclusion: Our study demonstrates that the sensitivity and specificity of HE4 was higher than that of cancer antigen 125. The results indicated that HE4 could be a useful tumor marker for ovarian cancer diagnosis. However, the results of this meta-analysis should be interpreted with caution, due to the heterogeneity among study designs. Further study should pay more attention to the possibility that HE4 can be a marker for monitoring recurrence of ovarian cancer. [ABSTRACT FROM AUTHOR]

The Tibetan population, long a resident on the Qinghai-Tibetan Plateau, has lower hemoglobin concentrations than Han Chinese migrants, but it is incompletely known how gender affects the hemoglobin concentrations in the two populations at various altitudes. Measurements of hemoglobin concentration were obtained in 5,887 healthy male and female Tibetan and Han residents aged 5–60 yr, at altitudes of 2,664, 3,813, 4,525, and 5,200 m. Multiple regression equations showed the n-coefficients for altitude and for age were higher (P < 0.05) in Han men than in Tibetan men and in Han women than in Tibetan women. Analysis indicated a significant three-way interaction between altitude, gender, and ethnicity (X2 = 3.72, P = 0.05). With increasing altitude, men progressively had more hemoglobin than women in the Han, but not the Tibetan, population. Above 2,664 m, this gender-related difference in hemoglobin concentration increased from childhood to young adulthood more in Han than in Tibetans. We suggest that the Han-Tibetan ethnic difference in the effect of altitude on hemoglobin concentration depends to a large extent on gender. [ABSTRACT FROM AUTHOR]