ObjectiveFibroblast activation protein (FAP) plays a vital role in tumor invasion and metastasis. Previous studies have reported its prognostic value in different tumors. However, the results of these reports remain controversial. In this study, a meta-analysis was performed to clarify this issue.MethodsA search of the PubMed, Embase and CNKI databases was conducted to analyze relevant articles. The outcomes included the relations between FAP expression and histological differentiation, tumor invasion, lymph node metastasis, distant metastasis and overall survival (OS). Sensitivity analysis by FAP expression in different cells and tumor types were further subjected to sensitivity analyses as subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using the random-effects model.ResultsThe global analysis included 15 studies concerning various solid tumors. For global analysis, FAP overexpression in tumor tissue displayed significant associations with poor OS and tumor progression (OS: HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable results. First, the relation between FAP overexpression and poor OS and tumor lymph node metastasis was closer in the patients with FAP expression in tumor cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers all indicated that FAP overexpression was associated with a detrimental OS (HR: 1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect was not statistically significant compared with that in patients with non-colorectal cancers or non-pancreatic cancers. These analyses did not display a statistically significant correlation between FAP expression and histological differentiation and distant metastasis in all of the groups.ConclusionsFAP expression is associated with worse prognosis in solid tumors, and this association is particularly pronounced if FAP overexpression is found in the tumor cells rather than the stroma.

The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. However, it remains unclear how IL-17 might contribute to tumor angiogenesis. In our study, IL-17 enhanced the formation of vessel-like tubes in HUVECs both directly (when HUVECs were incubated with IL-17) and indirectly (when HUVECs were incubated in conditioned cell media (CCM) from IL-17-treated cancer cells). Our results from experiments using siRNA-mediated knockdowns of STAT3 and GIV suggest that the effects of IL-17 were mediated by activating STAT3/GIV signaling in NSCLC cells and subsequently up-regulating its downstream target VEGF. Consistent with these findings, immunostaining experiments on human NSCLC tissues indicated that IL-17 and GIV expression were significantly and positively associated with increased tumor vascularity. The clinical significance of IL-17 was authenticated by our finding that the combination of intratumoral IL-17 + cells and GIV expression served as a better prognosticator for survival than either marker alone. Therefore, our finding highlights a novel aspect of STAT3/GIV pathway in the IL-17 promotes tumor angiogenesis of NSCLC.

BackgroundAndrogen receptor (AR) is a promising therapeutic target for breast cancer. However, its prognostic value remains controversial in triple negative breast cancer (TNBC). Here we present a meta-analysis to investigate the correlation between AR expression and TNBC prognosis.ResultsThirteen relevant studies with 2826 TNBC patients were included. AR positive rate was 24.4%. AR+ patients tended to have lower tumor grade (p< 0.001), but more lymph node metastases (p < 0.01). AR positivity was associated with prolonged disease free survival (HR 0.809, 95% CI = 0.659-0.995, p < 0.05), but had no significant impact on overall survival (HR 1.270, 95% CI=0.904-1.782, p = 0.168). No difference in survival existed between subgroups using different AR or estrogen receptor cutoff values.Materials and methodsLiterature search was performed in Pubmed, Embase and Cochrane Central Register of Controlled Trials databases to identify relevant articles on AR and TNBC prognosis. Fixed- and random-effect meta-analyses were conducted based on the heterogeneity of included studies. Heterogeneity and impacts of covariates were further evaluated by subgroup analyses and meta-regression.ConclusionAR positivity is associated with lower risk of disease recurrence in TNBC. Further clinical studies are warranted to clarify its prognostic role on TNBC recurrence and survival.

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Keloid is a skin fibrotic disease with the characteristics of recurrence and invasion, its pathogenesis still remains unrevealed. The epithelial-mesenchymal transition (EMT) is critical for wound healing, fibrosis, recurrence, and invasion of cancer. We sought to investigate the EMT in keloid and the mechanism through which the EMT regulates keloid formation. In keloid tissues, the expressions of EMT-associated markers and transforming growth factor (TGF)-β1/Smad3 signaling were examined by immunohistochemistry. In the keloid epidermis and dermal tissue, the expressions of genes related to the regulation of skin homeostasis, fibroblast growth factor receptor 2 (FGFR2) and p63, were analyzed using quantitative real-time polymerase chain reaction. The results showed that accompanying the loss of the epithelial marker E-cadherin and the gain of the mesenchymal markers fibroblast-specific protein 1 (FSP1) and vimentin in epithelial cells from epidermis and skin appendages, and in endothelial cells from dermal microvessels, enhanced TGF-β1 expression and Smad3 phosphorylation were noted in keloid tissues. Moreover, alternative splicing of the FGFR2 gene switched the predominantly expressed isoform from FGFR2-IIIb to -IIIc, concomitant with the decreased expression of ΔNp63 and TAp63, which changes might partially account for abnormal epidermis and appendages in keloids. In addition, we found that TGF-β1-induced hair follicle outer root sheath keratinocytes (ORSKs) and normal skin epithelial cells underwent EMT in vitro with ORSKs exhibiting more obvious EMT changes and more similar expression profiles for EMT-associated and skin homeostasis-related genes as in keloid tissues, suggesting that ORSKs might play crucial roles in the EMT in keloids. Our study provided insights into the molecular mechanisms mediating the EMT pathogenesis of keloids.

Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value.

Abstract. MicroRNAs (miRNAs) are often aberrantly expressed in breast cancer and are postulated to play a role in its initiation and progression. In the present study, we found that the expression level of miR-24-3p was upregulated in breast cancer in comparison with the level in adjacent normal tissues. Overexpression of miR-24-3p was able to promote cell proliferation and inhibit cell apoptosis in MDA-MB-435 and MDA-MB-468 cells. With the bioinformatic method, we further identified that p27Kip1 is a direct target of miR-24-3p, and its protein level was negatively regulated by miR-24-3p. Therefore, the data reported here demonstrate that miR-24-3p is an important regulator in breast cancer, and imply that the miR-24-3p/p27Kip1 axis has potential as a therapeutic target for breast cancer.

Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a