Identification of characteristics and construction of nomogram to predict the survival probability of mesonephric carcinoma patients: A population-based analysis and a case report.

BACKGROUND: Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of published guidelines. OBJECTIVE: To summarize the characteristics and construct an external-validated nomogram to predict the survival of MC patients. METHOD: Sixty-four qualified patients derived from the Surveillance, Epidemiology, and End Results Plus database, and one patient from the Guangzhou Red Cross Hospital were enrolled. The entire cohort was randomly divided into a development (70%) and a validation cohort (30%). The Kaplan-Meier method and univariate and multivariate Cox regression analyses were applied. Two nomograms were established to predict the 3-to-8-year survival probability of MC patients, which were evaluated by C-index, ROC curves, DCA curves, and calibration plots. RESULTS: The average survival time of MC patients was 84.22 ± 50.66 months. No significant difference was shown among different groups of race, primary site, tumor differentiated grade, and FIGO stages, while different SEER stages did distinguish patients' survival time, which indicated that the SEER stage standards might be a better staging system in the MC patients than FIGO stage (p = .0835). Additional survival analyses showed that MC patients benefited from shorter waiting times to begin treatment, accepting surgery, regional lymph node examination, radiotherapy, and chemotherapy. Two nomograms were established, both of which got satisfied scores in C-index, ROC curves, DCA curves, and calibration plots. CONCLUSION: Sufficient regional lymph nodes examined, and applying radiotherapy in high-risk patients are recommended in MC patients. Nomograms established in the present study had good predicting and discriminating capabilities, which would be helpful in patients' individual risk estimation, management, counseling, and follow-up.

Two tripartite classification systems of CD86+ and CD206+ macrophages are significantly associated with tumor recurrence in stage II-III colorectal cancer.

Introduction: The prognostic value of tumor-associated macrophages remains unclear in colorectal cancer (CRC). Two tripartite classification systems, namely, ratio and quantity subgroups, were investigated as the prognostic stratification tools for stage II-III CRC. Methods: We assessed the infiltration intensity of CD86+ and CD206+ macrophages in 449 cases with stage II-III disease by immunohistochemical staining. Ratio subgroups were defined by the lower- and upper-quartile points of CD206+/(CD86++CD206+) macrophage ratio, including the low-, moderate-, and high-ratio subgroups. Quantity subgroups were defined by the median points of CD86+ and CD206+ macrophages and included the low-, moderate-, and high-risk subgroups. The main analysis was recurrence-free survival (RFS) and overall survival (OS). Results: Ratio subgroups (RFS/OS: HR=2.677/2.708, all p<0.001) and quantity subgroups (RFS/OS: HR=3.137/3.250, all p<0.001) could serve as independent prognostic indicators that effectively predicted survival outcomes. More importantly, log-rank test revealed that patients in the high-ratio (RFS/OS: HR=2.950/3.151, all p<0.001) or high-risk (RFS/OS: HR=3.453/3.711, all p<0.001) subgroup exhibited decreased survival outcomes after adjuvant chemotherapy. The predictive accuracy of the quantity subgroups within 48 months was higher than that of the ratio subgroups and tumor stage (all p<0.05). Conclusions: Ratio and quantity subgroups could serve as independent prognostic indicators that could potentially be incorporated into the tumor staging algorithm to improve prognostic stratification and provide better predictions of survival outcomes in stage II-III CRC after adjuvant chemotherapy.

Development and validation of nomograms to predict the survival probability and occurrence of a second primary malignancy of male breast cancer patients: a population-based analysis.

Background: Male breast cancer (MBC) is rare, which has restricted prospective research among MBC patients. With effective treatments, the prognosis of MBC patients has improved and developing a second primary malignancy (SPM) has become a life-threatening event for MBC survivors. However, few studies have focused on the prognosis of MBC patients and looked into the SPM issue in MBC survivors. Method: We reviewed MBC patients diagnosed between 1990 and 2016 from the latest Surveillance, Epidemiology, and End Results (SEER) Plus database. Competing risk models and nomograms were conducted for predicting the risk of cancer-specific death and SPM occurrence. C-indexes, calibration curves, ROC curves, and decision curve analysis (DCA) curves were applied for validation. Result: A total of 1,843 MBC patients with complete information were finally enrolled and 60 (3.26%) had developed an SPM. Prostate cancer (40%) was the most common SPM. The median OS of all the enrolled patients was 102.41 months, while the median latency from the initial MBC diagnosis to the subsequent diagnosis of SPM was 67.2 months. The patients who suffered from an SPM shared a longer OS than those patients with only one MBC (p = 0.027). The patients were randomly divided into the development cohort and the validation cohort (at a ratio of 7:3). The Fine and Gray competing risk model was used to identify the risk factors. Two nomograms were constructed and validated to predict the 5-year, 8-year, and 10-year survival probability of MBC patients, both of which had good performance in the C-index, ROC curves, calibration plots, and DCA curves, showing the ideal discrimination capability and predictive value clinically. Furthermore, we, for the first time, constructed a nomogram based on the competing risk model to predict the 5-year, 8-year, and 10-year probability of developing an SPM in MBC survivors, which also showed good discrimination, calibration, and clinical effectiveness. Conclusion: We, for the first time, included treatment information and clinical parameters to construct a nomogram to predict not only the survival probability of MBC patients but also the probability of developing an SPM in MBC survivors, which were helpful in individual risk estimation, patient follow-up, and counseling in MBC patients.

Extracellular vesicles derived from cervical cancer cells carrying MCM3AP-AS1 promote angiogenesis and tumor growth in cervical cancer via the miR-93/p21 axis.

Tumor cells can promote angiogenesis by secreting extracellular vesicles (EVs). Meanwhile, tumor-derived EVs can carry long non-coding RNAs to activate pro-angiogenic signaling in endothelial cells. Here, we investigated the role of long non-coding RNA MCM3AP-AS1 carried by cervical cancer (CC) cell-derived EVs in the angiogenesis and the resultant tumor growth in CC, as well as the potential molecular mechanisms. LncRNAs significantly expressed in CC cell-derived EVs and CC were screened, followed by prediction of downstream target genes. EVs were isolated from HcerEpic and CaSki cell supernatants, followed by identification. The expression of MCM3AP-AS1 in CC was analyzed and its interaction with miR-93-p21 was confirmed. Following co-culture system, the role of MCM3AP-AS1 carried by EVs in HUVEC angiogenic ability, CC cell invasion and migration in vitro along with angiogenesis and tumorigenicity in vivo was assayed. MCM3AP-AS1 was overexpressed in CC cell-derived EVs as well as in CC tissues and cell lines. Cervical cancer cell-derived EVs could transfer MCM3AP-AS1 into HUVECs where MCM3AP-AS1 competitively bound to miR-93 and upregulate the expression of the miR-93 target p21 gene. Thus, MCM3AP-AS1 promoted angiogenesis of HUVECs. In the similar manner, MCM3AP-AS1 enhanced CC cell malignant properties. In nude mice, EVs-MCM3AP-AS1 induced angiogenesis and tumor growth. Overall, this study reveals that CC cell-derived EVs may transport MCM3AP-AS1 to promote angiogenesis and tumor growth in CC.

High Infiltration of CD203c+ Mast Cells Reflects Immunosuppression and Hinders Prognostic Benefit in Stage II-III Colorectal Cancer.

Background: Activated mast cells (AMCs) have been fully researched in inflammation and allergic reactions. However, the protumoral role of AMCs and their biomarker CD203c has not yet been investigated in colorectal cancer (CRC). Methods: We retrospectively collected 449 postoperative patients with stage II-III CRC at two different hospitals as the training (n=310) and validation (n=139) cohorts. These findings were further validated in the independent cohort (Integration of GSE39582 and GSE17536, n=489). The AMC density was assessed using CD203c staining or the CIBERSORT method. The main analysis was recurrence-free survival (RFS) and overall survival (OS). Results: As an independent factor, high AMC infiltration was associated with worse RFS/OS in the training (hazard ratio [HR]=3.437/3.014, all p<0.001) and validation (HR=3.537/2.382, all p<0.001) cohorts. We developed and validated an AMC-based nomogram for better stratification for postoperative recurrence in these two cohorts. The role of AMC density was further validated in the independent cohort. High AMC infiltration was associated with decreased RFS/OS after adjuvant chemotherapy (all p<0.05). Approximately 74.2% of intramural CD203c+ AMCs expressed a high level of PD-L1. Multiple immunosuppressive pathways were enriched in high AMC infiltration tumors, including upregulation of the TNF-α/NF-κB and angiogenesis pathways and downregulation of the IFN-γ and IFN-α responses. AMC infiltration was reversely associated with CD8+ T-cell infiltration (all p<0.05). Conclusion: High AMC infiltration is associated with worse survival outcomes in stages II-III CRC. AMC density may serve as a potential biomarker for survival benefit in patients receiving adjuvant chemotherapy. This AMC-based nomogram could provide better recurrence stratification. Immunosuppression in tumors with high AMC infiltration might contribute to promoting tumor progression.

Comparison of whole-body 18F-FDG PET/CT and PET/MRI for distant metastases in patients with malignant tumors: a meta-analysis.

BACKGROUND: As a first-line imaging modality, whole-body fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET/magnetic resonance imaging (MRI) had been widely applied in clinical practice. However, 18F-FDG PET/MRI may be superior to PET/CT for the diagnosis of distant metastases in patients with advanced-stage. Therefore, it is timely and important to systematically determine the diagnostic accuracy of 18F-FDG PET/MRI compared with that of 18F-FDG PET/CT for the diagnosis of distant metastases. METHODS: This study aimed to compare the diagnostic accuracy of 18F-FDG PET/CT and PET/MRI for the diagnosis of distant metastases in patients with malignant tumors. Relevant studies using both 18F-FDG PET/CT and PET/MRI for assessment of distant metastases in patients with malignant tumors were searched in PubMed, Embase, The Cochrane Library, and Scopus from January 2010 to November 2023. Two reviewers independently selected studies according to the inclusion and exclusion criteria. A reviewer extracted relevant data and assessed the quality of the eligible studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the summary receiver operating characteristic curve (AUC) for 18F-FDG PET/CT and PET/MRI were analyzed. Subgroup analysis was performed. RESULTS: Across 14 studies (1042 patients), 18F-FDG PET/MRI had a higher sensitivity (0.87 versus 0.81), AUC value (0.98 versus 0.95), and similar specificity (0.97 versus 0.97), than PET/CT for detecting distant metastases. In 3 studies of breast cancer (182 patients), 18F-FDG PET/MRI had a higher sensitivity (0.95 versus 0.87) and specificity (0.96 versus 0.94) than PET/CT. In 5 studies of lung cancer (429 patients), 18F-FDG PET/CT had a higher sensitivity (0.87 versus 0.84) and a lower specificity (0.95 versus 0.96) to PET/MRI. CONCLUSIONS: 18F-FDG PET/MRI and PET/CT both performed well as detectors of distant metastases in patients with malignant tumors, and the former has higher sensitivity. The subgroup analysis highlights that 18F-FDG PET/MRI and PET/CT hold different advantages for distant metastases staging in different tumors, PET/MRI has a higher accuracy in patients with breast cancer patients, while PET/CT has a higher accuracy in patients with lung cancer.

The Ratio of CD86+/CD163+ Macrophages Predicts Postoperative Recurrence in Stage II-III Colorectal Cancer.

Tumor-associated macrophages (TAMs) are pivotal for tumor progression and metastasis. We investigated the stromal CD86+TAM/CD163+TAM (CD86/CD163) ratio as a novel prognostic biomarker for stage II-III colorectal cancer (CRC). Two independently clinical cohorts of stage II-III CRC were retrospectively enrolled in this study. TAMs were detected using immunohistochemical staining for CD86 and CD163. The stromal CD86/CD163 ratio was calculated as a prognostic biomarker for recurrence-free survival (RFS) and overall survival (OS). Patients with a low CD86/CD163 ratio had shorter RFS (HR=0.193, p<0.001) and OS (HR=0.180, p<0.001) than patients with a high CD86/CD163 ratio in the training cohort. CD86/CD163 ratio may be an independent predictor for RFS (HR=0.233, p<0.001) and OS (HR=0.224, p<0.001) in the training cohort. We obtained equivalent results in the validation cohort. The CD86/CD163 ratio tends to have better predictive values than tumor stage in the training (AUC: 0.682 vs 0.654, p=0.538) and validation (AUC: 0.697 vs 0.659, p=0.586) cohorts. CD86/CD163 ratio effectively predicts RFS for stage II (HR=0.203, p<0.001) and stage III CRC (HR=0.302, p<0.001). CD86/CD163 ratio also effectively predicts RFS in CRC patients with adjutant chemotherapy (HR=0.258, p<0.001) and without adjutant chemotherapy (HR=0.205, p<0.001). The stromal CD86/CD163 ratio could be used for individual risk assessment of recurrence and mortality for stage II-III CRC. Together with tumor stage, this ratio will aid in the personal treatment.

Development of prognostic index based on autophagy-related genes analysis in breast cancer.

BACKGROUND: Autophagy is a self-digesting process that can satisfy the metabolic needs of cells, and is closely related to development of cancer. However, the effect of autophagy-related genes (ARGs) on the prognosis of breast cancer remains unclear. RESULTS: We first found that 27 ARGs were significantly associated with overall survival in breast cancer. The prognosis-related ARGs signature established using the Cox regression model consists of 12 ARGs that can be divided patients into high-risk and low-risk groups. The overall survival of patients with high-risk scores (HR 3.652, 2.410-5.533; P < 0.001) was shorter than patients with low-risk scores. The area under the receiver operating characteristic (ROC) curve for 1-year, 3-year, and 5-year survival rates were 0.739, 0.727, and 0.742, respectively. CONCLUSION: The12-ARGs marker can predict the prognosis of breast cancer and thus help individualized treatment of patients at different risks. METHODS: Based on the TCGA dataset, we integrated the expression profiles of ARGs in 1,039 breast cancer patients. Differentially expressed ARGs and survival-related ARGs were evaluated by computational difference algorithm and COX regression analysis. In addition, we also explored the mutations in these ARGs. A new prognostic indicator based on ARGs was developed using multivariate COX analysis.

LncRNA MCM3AP-AS1 inhibits cell proliferation in cervical squamous cell carcinoma by down-regulating miRNA-93.

BACKGROUND: MCM3AP antisense RNA 1 (MCM3AP-AS1) is characterized as an oncogenic lncRNA in hepatocellular carcinoma and glioblastoma. We analyzed TCGA dataset and observed the down-regulation of MCM3AP-AS1 in cervical squamous cell carcinoma (CSCC). The present study was therefore performed to investigate the role of MCM3AP-AS1 in CSCC. METHODS: A total of 64 female patients with CSCC (38-68 years old; mean age: 53.1 ± 6.5 years old) were enrolled in the present study. RT-qPCR was performed to evaluate gene expression. Methylation specific PCR (MSP) was performed to assess the methylation of miR-93 gene after the overexpression and silencing of MCM3AP-AS1. Cell transfections were performed to investigate the interactions between MCM3AP-AS1 and miR-93. Cell proliferation was assessed by CCK-8 assay. RESULTS: The results showed that MCM3AP-AS1 was down-regulated in CSCC and predicted poor survival. The expression levels of MCM3AP-AS1 were inversely correlated with the expression levels of miR-93. Overexpression of MCM3AP-AS1 led to down-regulation of miR-93, while silencing of MCM3AP-AS1 played an opposite role in CSCC cells. Methylation-specific PCR revealed that MCM3AP-AS1 could positively regulate the methylation of miR-93 gene. Cell proliferation analysis showed that overexpression of MCM3AP-AS1 led to reduced proliferation rate of CSCC cells. Silencing of MCM3AP-AS1 played an opposite role and overexpression of miR-93 reduced the effects of overexpressing MCM3AP-AS1. CONCLUSIONS: Therefore, MCM3AP-AS1 may inhibit cell proliferation in CSCC by down-regulating miRNA-93.

Young age at diagnosis is associated with better prognosis in stage IV breast cancer.

Numerous studies have shown that young age is a risk factor in early breast cancer. But for stage IV breast cancer, it is unclear whether age has a similar effect on patient survival. We collected and analyzed data from patients with stage IV breast cancer between January 2010 and December 2015 in SEER database. Multivariate Cox proportional hazard model was used in this study. 13,069 patients with stage IV breast cancer were included in the analysis, of which 1,135 were young breast cancer patients (≤40 years old). In a multivariate analysis that adjusted for sociodemographic factors, clinical-pathological characteristics and therapeutic methods, the risk of death in patients with stage IV ≤40 years was significantly reduced (hazard ratio [HR], 0.72; 95% CI, 0.65-0.79). Subgroup analyses showed that, with the same adjustment of all factors, young age only significantly reduced the risk of death in patients with luminal A (HR, 0.78; 95% CI, 0.68-0.89) and luminal B (HR 0.46; 95% CI, 0.35-0.60) subtypes. Young age at diagnosis is associated with better survival in patients with stage IV breast cancer. The effect of young age at diagnosis on the survival outcome of stage IV breast cancer varies by subtypes.