Clinicopathological value of long non-coding RNA profiles in gastrointestinal stromal tumor.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been implicated in diagnosis and prognosis in various cancers. However, few lncRNA signatures have been established for prediction of gastrointestinal stromal tumors (GIST). We aimed to explore a lncRNA signature profile that associated with clinical relevance by mining data from Gene Expression Ominus (GEO) and Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: Using a lncRNA-mining approach, we performed non-negative matrix factorization (NMF) consensus algorithm in Gastrointestinal stromal tumors (GISTs) cohorts (61 patients from GSE8167 and GSE17743) to cluster LncRNA expression profiles. Comparative markers selection, and Gene Set Enrichment Analysis (GSEA) algorithm were performed between distinct molecular subtypes of GIST. The survival rate of GIST patients from SEER stratified by gender were compared by Kaplan-Meier method and log-rank analysis. lncRNA-mRNA co-expression analysis was performed by Pearson correlation coefficients (PCC) using R package LINC. Somatic copy number alterations of GIST patients (GSE40966) were analyzed via web server GenePattern GISTIC2 algorithm. RESULTS: A total of four lncRNA molecular subtypes of GIST were identified with distinct biological pathways and clinical characteristics. LncRNA expression profiles well clustered the GIST samples into small size (<5 mm) and large size tumors (>5 mm), which is a fundamental index for GIST malignancy diagnosis. Several lncRNAs with abundant expression (LRRC75A-AS1, HYMAI, NEAT1, XIST and FTX) were closely associated with tumor size, which may suggest to be biomarkers for the GIST malignancy. Particularly, LRRC75A-AS1 was positively associated with tumor diameters and suggested an oncogene in GIST. Co-expression analysis suggested that chromosome region 17p11.2-p12 may contribute to the oncogenic process in malignant GIST. Interestingly, the gender had a strong influence on clustering by lncRNA expression profile. Data from the Surveillance, Epidemiology, and End Results (SEER) Program were further explored and 7983 patients who were diagnosed with GISTs from 1973 to 2014 were enrolled for analysis. The results also showed the favorable prognosis for female patients. The survival rate between male and female with GIST was statistically significant (P < 0.0001). Gene set enrichment analysis (GSEA) indicated distinct pathways between female and male, and malignant GIST was associated with several cancer metabolism and cell cycle associated pathways. CONCLUSIONS: This lncRNAs-based classification for GISTs may provide a molecular classification applicable to individual GIST that has implications to influence lncRNA markers selection and prediction of tumor progression.

A novel nomogram for predicting liver metastasis in patients with gastrointestinal stromal tumor: a SEER-based study.

BACKGROUND: Liver metastasis (LIM) of gastrointestinal stromal tumor (GIST) is associated with poor prognosis. The present study aimed at developing and validating nomogram to predict LIM in patients with GIST, thus helping clinical diagnosis and treatment. METHODS: The data of GIST patients derived from Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016, which were then screened by univariate and multivariate logistic regression for the construction of LIM nomogram. The model discrimination of LIM nomogram was evaluated by concordance index (C-index) and calibration plots, while the predictive accuracy and clinical values were measured by decision curve analysis (DCA) and clinical impact plot. Furthermore, we validated predictive nomogram in the internal testing set. RESULTS: A total of 3797 patients were enrolled and divided randomly into training and validating groups in a 3-to-1 ratio. After logistic regression, the significant variables were sex, tumor location, tumor size, N stage and mitotic rate. The calibration curves showed the perfect agreement between nomogram predictions and actual observations, while the DCA and clinical impact plot showed the clinical utility of LIM nomogram. C-index of the nomogram was 0.812. What's more, receiver operating characteristic curves (ROC) also showed good discrimination and calibration in the training set (AUC = 0.794, 95% CI 0.778-0.808) and the testing set (AUC = 0.775, 95% CI 0.748-0.802). CONCLUSION: The nomogram for patients with GIST can effectively predict the individualized risk of liver metastasis and provide insightful information to clinicians to optimize therapeutic regimens.

The effect of marital status on the survival of patients with colorectal neuroendocrine neoplasms: an analysis of the SEER database.

BACKGROUND: increasing evidence suggests that marital status is associated with tumor prognosis. The prognostic impact of marital status on colorectal neuroendocrine neoplasms has not been studied adequately. This study explored the relationship between marital status and prognosis of colorectal neuroendocrine neoplasms. METHODS: during 2004-2012, 7,180 colorectal neuroendocrine neoplasm patients were identified from the Surveillance, Epidemiology and End Results database. A primary comparison (married vs unmarried) was performed with a 1:1 propensity matching score. Secondary comparisons were performed individually between three unmarried subgroups (single, divorced/separated, widowed) and the married group. The effect of marital status according to sex and extension of disease was explored. RESULTS: married patients had better survival (overall survival) (p < 0.001) and colorectal neuroendocrine neoplasm cause-specific survival (p = 0.001) rates compared to unmarried patients. Multivariate analysis indicated that marital status was an independent prognostic factor and married patients had a better overall survival (HR = 1.673; 95% CI: 1.446-1.936; p < 0.001) and colorectal neuroendocrine neoplasm cause-specific survival (HR = 1.365; 95% CI: 1.141-1.632; p = 0.001). Subgroup analysis showed that married patients had the best prognosis of cause-specific survival/overall survival and widowed patients had the worst prognosis (log-rank test p < 0.05). Marital status plays a more important role in colorectal neuroendocrine neoplasms patients with localized disease than in those with regional or distant disease. CONCLUSIONS: marital status is an independent prognostic factor for survival in colorectal neuroendocrine neoplasms patients. Married patients have a better prognosis with early stage disease. Single, widowed and male patients are regarded as a high-risk population.