A novel miRNA-based signature as predictive tool of survival outcome of colorectal cancer patients.

It is great significance of identifying valuable biomarkers for early diagnosis and prognostic prediction of colorectal cancer (CRC) patients. This study aimed at developing and validating a miRNAs-based signature as prognostic tool for CRC patients. The miRNA expression profile of 624 CRC samples (613 tumor tissues and 11 normal tissues) was analyzed, and 523 differentially expressed miRNAs (DEmiRNAs) were identified, in which 191 were downregulated and 332 were upregulated. All patients were randomly divided into a training cohort (N = 308) and an internal validation cohort (N = 200). Using the least absolute shrinkage and selection operator (LASSO) and Cox regression model, a prognostic signature of 10 miRNAs (hsa-miR-149-5p, hsa-miR-193b-5p, hsa-miR-193a-3p, hsa-miR-3677-3p, hsa-miR-29a-3p, hsa-miR-200c-5p, hsa-miR-200a-5p, hsa-miR-6854-5p, hsa-miR-216a-5p and hsa-miR-891a-5p) was developed in the training cohort. The risk score was calculated by the product of the expression level and the coefficients of each miRNA. The prognostic value of 10 miRNAs-based signature for CRC patients was tested and validated. Survival analysis indicated that high-risk patients (> 1.10) had a worse overall survival (OS) than low-risk (≤ 1.10) patients (5-year OS rate for training cohort: 59.3% vs. 78.9%, p < .001; validation cohort: 48.3% vs. 69.3%, p = .011). The miRNA-based signature was an independent prognostic factor for CRC patients (HR for training cohort:2.476, 95% CI:1.202-5.098, p = .014; HR for validation cohort:2.050, 95% CI:1.087-3.869, p = .027). The AUC values for 3-year and 5-year OS prediction were 0.718 and 0.784 in the training cohort, 0.659 and 0.614 in the validation cohort, respectively. The 10 miRNAs-based signature provided a proper prognostic stratification for CRC patients, and it might be a promising tool for survival prediction.

Development and validation of a prognostic nomogram for rectal cancer patients who underwent surgical resection.

Objective: The purpose of this study was to develop and validate a nomogram model for the prediction of survival outcome in rectal cancer patients who underwent surgical resection. Methods: A total of 9,919 consecutive patients were retrospectively identified using the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were determined by the univariate and multivariate Cox analysis. The nomogram model for the prediction of cancer-specific survival (CSS) in rectal cancer patients were developed based on these prognostic variables, and its predictive power was assessed by the concordance index (C-index). Calibration curves were plotted to evaluate the associations between predicted probabilities and actual observations. The internal and external cohort were used to further validate the predictive performance of the prognostic nomogram. Results: All patients from the SEER database were randomly split into a training cohort (n = 6,944) and an internal validation cohort (n = 2,975). The baseline characteristics of two cohorts was comparable. Independent prognostic factors were identified as age, pT stage, lymph node metastasis, serum CEA level, tumor size, differentiation type, perineural invasion, circumferential resection margin involvement and inadequate lymph node yield. In the training cohort, the C-index of the nomogram was 0.719 (95% CI: 0.696-0.742), which was significantly higher than that of the TNM staging system (C-index: 0.606, 95% CI: 0.583-0.629). The nomogram had a C-index of 0.726 (95% CI: 0.691-0.761) for the internal validation cohort, indicating a good predictive power. In addition, an independent cohort composed of 202 rectal cancer patients from our institution were enrolled as the external validation. Compared with the TNM staging system (C-index: 0.573, 95% CI: 0.492-0.654), the prognostic nomogram still showed a better predictive performance, with the C-index of 0.704 (95% CI: 0.626-0.782). Calibration plots showed a good consistency between predicted probability and the actual observation in the training and two validation cohorts. Conclusion: The nomogram showed an excellent predictive ability for survival outcome of rectal cancer patients, and it might provide an accurate prognostic stratification and help clinicians determine individualized treatment strategies.

Mixed adenoneuroendocrine carcinoma originating from the appendix and colorectum: a comparative analysis of a large population-based database.

PURPOSE: As a rare gastrointestinal neoplasm, the demographic, clinicopathological, and prognostic characteristics of mixed adenoneuroendocrine carcinoma (MANEC) remain unclear. The purpose of this study was to evaluate its biological features, survival outcome, and prognostic factors. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, we retrospectively reviewed clinicopathological and survival data of 513 patients who were histopathologically diagnosed with MANEC of the appendix and colorectum bettween 2004 and 2015. The clinicopathological features and survival outcomes of MANEC located at different anatomical locations were compared, and predictive factors for cancer-specific survival (CSS) and overall survival (OS) were assessed. RESULTS: In terms of anatomical distribution of MANEC, the appendix (64.5%, 331/513) was more frequently involved, followed by colon (28.1%, 144/513) and rectum (7.4%, 38/513). The MANEC at different anatomical locations had a distinct clinicopathological characteristic, and colorectal MANEC was significantly associated with more aggressive biological features. The survival outcomes of appendiceal MANEC were significantly better than that of colorectal MANEC (3-year CSS rate 73.8% vs 59.4%, P = 0.010; 3-year OS 69.2% vs 48.3%, P < 0.001). In addition, hemicolectomy had a better survival benefit than appendicectomy for patients with appendiceal MANEC, regardless of lymph node metastasis (P < 0.05). Tumor location, histology grade III, tumor size > 2 cm, T3-T4 stage, lymph node metastasis, and distant metastasis were independent prognostic factors for patients with MANEC. CONCLUSIONS: Tumor location had an important prognostic significance for MANEC. As an uncommon clinical entity, colorectal MANEC had more aggressive biological features and worse prognosis than its appendiceal counterpart. The standard surgical procedure and clinical management strategy for MANEC need to be established.

Malignant rhabdoid tumor of the liver in a middle-aged woman: a case report and literature review.

BACKGROUND: Extrarenal malignant rhabdoid tumor (EMRT) is a rare and high-mortality malignant tumor, which is more common in infants and rarely seen in adults. We firstly report a case of liver malignant rhabdoid tumor (MRT) with a loss of SMARCB1 gene (alias INI1, SNF5, BAF47) expression in a middle-aged woman, and preliminarily summarize the clinical characteristics and discuss its potential treatment of liver MRT by reviewing 55 cases reported in the past. CASE PRESENTATION: We report a 40-year-old woman who was admitted to our hospital for right epigastric pain. Previously, the patient was treated with liver hematoma in another hospital until she came to our hospital for abdominal pain again. In our hospital, we performed surgical treatment on her and the pathology diagnosed EMRT with negative expression of SMARCB1. After surgery, the patient underwent genetic testing, but failed to screen for sensitive targeted or conventional chemotherapy drugs, and she did not receive further treatment. Due to lack of timely diagnosis and effective chemotherapy drugs, tumor recurrence and metastasis occurred one year after surgery. Then the patient chose traditional Chinese medicine for treatment. And the metastatic tumors had still progressed after one year of treatment, but the patient didn't have obvious discomfort symptoms. CONCLUSIONS: Liver MRT is a highly aggressive tumor with high metastatic potential and poor prognosis. It lacks specific symptoms and signs and is easy to be ignored and misdiagnosed. The mortality rate is extremely high as there is no effective treatment. But most tumors are accompanied by SMARCB1 deficiency, which may offer new research directions for cancer therapeutics. For the present, early detection, early diagnosis and early resection remain the key to improve the prognosis of patients.