Though proposed as a promising target antigen for cancer immunotherapy, the prognostic value of Wilms' tumor 1 (WT1) in solid tumors remains inconclusive. Here, we report a systematic review and meta-analysis of the association between WT1 expression and prognosis in solid tumors. PubMed, Web of Science and Google Scholar were searched to identify studies exploring the impact of WT1 on clinical outcomes, including overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), relapse/recurrence-free survival (RFS) or progression-free survival (PFS), in solid cancer patients. Hazard ratio (HR) and 95% confidence interval (CI) were applied to assess the strength of these associations. Finally, a total of 29 eligible studies with 4090 patients were identified for qualitative analysis, and 22 studies with 3620 patients were enrolled for quantitative synthesis. Overall, positive expression of WT1 was significantly associated with worse OS (metaHR = 1.48, 95% CI = 1.11–1.97) and DFS/RFS/PFS (metaHR = 2.14, 95% CI = 1.42–3.21). Subgroup analyses showed that WT1 positive expression could independently predict unfavorable DFS/RFS/PFS (metaHR = 1.86, 95%CI = 1.04–3.35). In summary, our study suggests that WT1 may be a potential marker to predict DFS/RFS/PFS in solid tumor patients. Further studies are needed to confirm the role of WT1 expression in clinical practice.

Tumor cells evolve by interacting with the local microenvironment; however, the tumor-stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates β-catenin, leading to translocation of β-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor-stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer.

PurposePARP inhibition is an exciting new anticancer strategy. As the first PARP inhibitor approved for the treatment of advanced BRCA-mutated ovarian cancer, olaparib has proven to be effective in the treatment of several solid tumors. We performed a meta-analysis of published randomized controlled trials to evaluate the efficacy and safety of olaparib in cancer patients.MethodsPubMed, Embase, and oncology-conference proceedings were searched for relevant studies. End points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 adverse events. Pooled hazard ratio (HR)/risk ratio (RR) and 95% CI were calculated using random or fixed-effect models.ResultsEight trials involving 1,957 patients were ultimately identified. The pooled analysis demonstrated that olaparib treatment significantly improved PFS (HR 0.62, 95% CI 0.47–0.82; P=0.001), OS (HR 0.82, 95% CI 0.73–0.93; P=0.001), and ORR (RR 1.38, 95% CI 1.16–1.65; P<0.001) when compared with therapy not containing olaparib. This association was further confirmed by sensitivity analysis. Additionally, olaparib treatment offered a significant survival benefit for patients with BRCA mutation. Moreover, treatment with olaparib was associated with a significant increase in risk of severe anemia.ConclusionOlaparib treatment has better treatment response compared with therapy not containing olaparib, whereas olaparib can increase the risk of severe anemia.

Lung cancer (LC) is the most common cause of cancer-related death among humans. 1-3 Low-dose computed tomography (CT) is often used to screen for LCs, but even so, most patients with LC present with advanced-stage disease that is not eligible for curative resection. 4 Indeed, under 20% of non-small-cell LC (NSCLC) patients are eligible to undergo curative surgical resection. 4 Patients not eligible for curative respective treatment instead typically undergo chemotherapy and/or radiotherapy, but traditional chemotherapy is not an effective approach to controlling inoperable NSCLC. 5,6 Additionally, external beam radiotherapy is generally associated with