Early identification of metastatic or recurrent colorectal cancer (CRC) patients who will be sensitive to FOLFOX (5‐FU, leucovorin and oxaliplatin) therapy is very important. We performed microarray meta‐analysis to identify differentially expressed genes (DEGs) between FOLFOX responders and nonresponders in metastatic or recurrent CRC patients, and found that the expression levels of WASHC4, HELZ, ERN1, RPS6KB1, and APPBP2 were downregulated, while the expression levels of IRF7, EML3, LYPLA2, DRAP1, RNH1, PKP3, TSPAN17, LSS, MLKL, PPP1R7, GCDH, C19ORF24, and CCDC124 were upregulated in FOLFOX responders compared with nonresponders. Subsequent functional annotation showed that DEGs were significantly enriched in autophagy, ErbB signaling pathway, mitophagy, endocytosis, FoxO signaling pathway, apoptosis, and antifolate resistance pathways. Based on those candidate genes, several machine learning algorithms were applied to the training set, then performances of models were assessed via the cross validation method. Candidate models with the best tuning parameters were applied to the test set and the final model showed satisfactory performance. In addition, we also reported that MLKL and CCDC124 gene expression were independent prognostic factors for metastatic CRC patients undergoing FOLFOX therapy.

RAB family proteins participate in the dynamic regulation of cellular membrane compartments and are dysregulated in a variety of tumor types, which may alter the biological properties of cancer cells such as proliferation, migration, and invasion. In our previous study, we found that Ras-related protein Rab-31 (RAB31) expression was increased in late-stage colorectal cancer (CRC). The role of RAB31 has never been investigated in CRC. In this study, we found that expression of RAB31 in the tumor stroma but not cancer cells of colon cancer predicted poor survival. RAB31 can be detected in primary cancer-associated fibroblasts (CAFs) and paired normal fibroblasts. Conditioned medium (CM) from RAB31 overexpressing CAFs significantly promoted migration of colon cancer cell lines in vitro and in vivo. This process may be mediated by paracrine action of hepatocyte growth factor (HGF), which was increased in the CM of RAB31-overexpressing CAFs. Blockade of HGF/MET signaling by drug inhibition, knockdown of mesenchymal to epithelial transition factor (MET) in RKO, or antibody neutralization of HGF abolished migration of RKO cells mediated by RAB31 expression in CAFs. We propose that in colon cancer, increased RAB31 expression in CAFs may contribute to tumor progression by regulating the secretion of HGF in the tumor stroma.

Localized nasopharyngeal cancer (NPC) is a highly curable disease, but the prognosis of certain cases is still poor. Distinguishing patients with a poor outcome is necessary when developing therapeutic strategies. The aim of this study was to investigate the characteristics of early death (ED) among patients with localized NPC, and to identify independent predictors of ED. Patients diagnosed with localized NPC were included from the Surveillance, Epidemiology, and End Results dataset, and univariate and multivariate logistic regression analyses were performed to identify ED predictors. A total of 752 patients with localized NPC were enrolled, including 198 cases of ED and 480 long-term survivors. Older age, unmarried status, and white race were risk factors for ED, whereas diagnosis in the recent period and undifferentiated non-keratinizing histology type were protective factors. In addition, for older patients, women and those without radiation treatment, there was less ED for married patients than unmarried patients. In conclusion, this population-based study provides an overview of the characteristics of ED patients with localized NPC. Age, race, marital status, year of diagnosis and histology type are risk factors for ED. Moreover, married patients are at a significantly lower risk of ED. This protective effect is especially pronounced in older people, women and those without radiation treatment.