Background: Vascular endothelial growth factor (VEGF) has been reported to serve as a promising prognostic marker in several cancers. This meta-analysis aims to assess the prognostic significance of VEGF in nasopharyngeal cancer (NPC).Methods: We conducted a systematic literature search of PubMed, Embase, and the Cochrane Library for observational studies published until June, 2018 to identify observational studies on the prognostic effect of tissue VEGF expression or serum VEGF level on the survival of NPC. The primary outcome measure assessed was overall survival (OS). The secondary outcomes included disease-free survival (DFS) or progression-free survival (PFS). Summary hazard ratio (HR) and its 95% confidence interval (95% CI) were derived using a random-effects model.Results: Out of 840 retrieved citations, 16 studies inclusive of 1,345 patients were included in the analysis of tissue VEGF expression and cancer survival. The pooled HRs for OS and DFS in patients with high VEGF expression were 2.07 (95% CI: 1.32–3.25) and 5.99 (95% CI: 2.66–13.48), respectively, with significant heterogeneity between studies (I2 = 79.1% for OS and 50.2% for DFS). Tissue high VEGF expression was not significantly associated with short RFS, PFS, or MFS. Five studies also investigated the prognostic effect between serum VEGF level and patient survival and found that high serum VEGF level was significantly associated with short OS for patients with NPC (HR 2.47, 95% CI 1.16–5.28), but not with short PFS (HR 1.47, 95% CI 0.92–2.35).Conclusions: Determination of tissue VEGF expression and serum VEGF level have the potential to serve as biomarkers and add prognostic information in NPC. Prospective analyses of associated data on VEGF expression and serum VEGF level in large NPC cohorts could be further conducted to advance our understanding of the relationship between VEGF and NPC outcomes.

Vascular endothelial growth factor C (VEGF‐C) has been reported to be responsible for the lymphatic vessel density, tumor staging and lymph node metastasis, resulting in the failure of nasopharyngeal carcinoma (NPC) after radiotherapy. Therefore, the aim of this study was to explore the effects and the underlying mechanism of VEGF‐C on the radiotherapy and in the human NPC cell lines CNE‐2. In our study, VEGF‐C silenced CNE‐2 cells were stably established. Different small interfering VEGF‐C (si‐VEGFC) were transfected into CNE‐2 cells and combined with 8 Gy X‐ray. The proliferation, cloning ability, DNA damage, and apoptosis of CNE‐2 cells were evaluated by counting kit‐8 (CCK‐8), colony‐forming assay, comet assays, and flow cytometry, respectively. Moreover, the VEGFC knockdown involved signaling pathways in CNE‐2 cells were predicted by polymerase chain reaction (PCR) array, and validated by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and Western blot analysis. Results demonstrated that silencing VEGF‐C combined with radiation can significantly inhibit the proliferation and cloning ability, while increase the apoptosis and DNA damage of CNE‐2 cells, thereby promote the radiosensitivity. Furthermore, the effects of silencing VEGF‐C probably through activating the NF‐kB signal pathway. In conclusion, the study demonstrated that VEGF‐C may be a potential target to increase the radiosensitivity in NPC by activating NF‐kB signaling.

Melanocortin 1 receptor (MC1R) is thought to be a marker of poor prognosis and a potential target for the treatment of melanoma. Studies have found that MC1R promotes several tumor behaviors, including cell proliferation and differentiation, pigment formation, and genome damage repair. Some single-nucleotide polymorphisms (SNPs) of MC1R are involved in the occurrence and development of melanoma. A few studies have reported a relationship between MC1R and colorectal cancer (CRC). In this research, our objective was to examine MC1R expression and MC1R SNPs and investigate their correlation with the clinicopathological features of human CRC tissues. We evaluated MC1R mRNA expression by performing bioinformatic analyses on human CRC expression datasets. We used Western blotting and RT-qPCR to compare MC1R expression in CRC tissues with that in normal tissues, and MC1R SNPs in CRC tissues were detected by PCR-direct sequencing (DS). The expression of MC1R was significantly decreased in CRC tissues compared with normal tissue, and its expression was negatively associated with P53 expression, MLH1 expression, and PMS2 expression, and high MC1R expression was significantly associated with microsatellite instability (MSI). MC1R SNPs were also associated with the clinicopathological characteristics of CRC; for example, the rs2228479 locus genotype was correlated with Ki67 status, and the rs885479 locus genotype was correlated with age and T stage. In conclusion, MC1R plays a crucial role in the progression of CRC and may be a marker of poor prognosis in CRC.

Cholecystokinin-2 receptor (CCK2R) has been proven to be a specific biomarker for colorectal malignancies. Immunotoxins are a valuable class of immunotherapy agents consisting of a targeting element and a bacterial or plant toxin. Previous work demonstrated that targeting CCK2R is a good therapeutic strategy for the treatment of colorectal cancer (CRC).In the present study, we developed a new version of CCK2Rtargeting immunotoxin GD9P using a targeted peptide, GD9, as the binding motif and a truncated Pseudomonas exotoxin A (PE38) as the cytokiller. BALB/c nude mice were treated with different doses of GD9P, and pharmacodynamics, pharmacokinetic, and toxicological data were obtained throughout this study. Compared to the parental immunotoxin rCCK8PE38, GD9P exhibited about 1.5-fold yield, higher fluorescence intensity, and increased antitumor activity against human CRC in vitro and in vivo. The IC 50 values of GD9P in vitro ranged from 1.61 to 4.55 nM. Pharmacokinetic studies were conducted in mice with a T 1/2 of 69.315 min. When tumor-bearing nude mice were treated with GD9P at doses ≥2 mg/kg for five doses, a rapid shrinkage in tumor volume and, in some cases, complete remission was observed. A preliminary safety evaluation demonstrated a good safety profile of GD9P as a Pseudomonas exotoxin A-based immunotherapy. The therapy in combination with oxaliplatin can increase the antitumor efficacy and reduce the toxic side effects caused by chemotherapy. In conclusion, the data support the use of GD9P as a promising immunotherapy targeting CCK2R-expressing colorectal malignancies.