A Comprehensive Multiomics Analysis Identified Ubiquilin 4 as a Promising Prognostic Biomarker of Immune-Related Therapy in Pan-Cancer.

Recently, it was reported that ubiquilin 4 (UBQLN4) alteration was associated with genomic instability in some cancers. However, whether UBQLN4 is a valuable biomarker for the prognosis of immunotherapy in pan-cancer was not identified. We evaluated the biologic and oncologic significance of UBQLN4 in pan-cancer at multiomics level, such as expression, mutation, copy number variation (CNV), methylation, and N6-methyladenosine (m6A) methylation. These omics data were obtained from several public databases, including Oncomine, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), Gene Set Cancer Analysis (GSCA), m6A-Atlas, CancerSEA, and RNAactDrug. We found that UBQLN4 mRNA and protein were overexpressed in most cancer types, and the expression, mutation, CNV, and methylation of UBQLN4 were associated with the prognosis of some cancers. Mechanistically, UBQLN4 was involved in angiogenesis, DNA damage, apoptosis, and the pathway of PI3K/AKT and TSC/mTOR. Moreover, UBQLN4 mRNA was significantly correlated with immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR). And, the correlation among UBQLN4 mRNA, CNV, and methylation and immune microenvironment was also identified. Furthermore, UBQLN4 was associated with the sensitivity of chemotherapy and targeted drugs at multiomics level. In conclusion, UBQLN4 was a promising prognostic biomarker of immune-related therapy in pan-cancer.

Efficacy and safety of anti-angiogenesis medicines for advanced soft tissue sarcoma: a meta-analysis.

BACKGROUND: Surgery-based treatment is the standard method for the early-stage soft tissue sarcoma (STS) with relatively good clinical outcome. However, the recurrence and metastasis decrease the survival of STS, regardless of surgery, radiotherapy, and chemotherapy. On the other hand, anti-angiogenesis treatments for STS have been clinically applied in recent years. To evaluate the safety and efficacy of anti-angiogenesis medicines for the treatment of advanced STS, we conducted a meta-analysis. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, Excerpta Medica Database, and China National Knowledge Infrastructure from inception to September 5, 2019. And finally, nine studies with 1,230 patients were included after rigorous screening. The endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse reactions (AEs). And we analyzed them with the risk ratio (RR) or the hazard ratio (HR). Moreover, heterogeneity and sensitivity were also analyzed. RESULTS: The pooled data showed that anti-angiogenesis medicines significantly benefited ORR [risk ratio (RR) =2.16, 95% CI: 1.47-3.17, P<0.001], and DCR (RR =1.68, 95% CI: 1.49-1.89, P<0.001), respectively, and improved the PFS (HR =0.50, 95% CI: 0.41-0.59, P<0.001), and OS (HR =0.77, 95% CI: 0.63-0.95, P<0.05), respectively. However, as for grade III or higher acute AEs, the antiangiogenic treatment increased morbidities of hypertension (RR =4.88, P<0.005), and diarrhea (RR =3.98, P=0.021) compared to the control group. And no significant difference was found in bone marrow inhibition, vomiting, anemia, and mucositis. CONCLUSIONS: Anti-angiogenesis treatments are beneficial in short-term efficacy and long-term survival for the recurrence and metastasis of STS, and the AEs are tolerable.

Krüppel-like factor 8 regulates VEGFA expression and angiogenesis in hepatocellular carcinoma.

Tumor angiogenesis plays a critical role in hepatocellular carcinoma (HCC) development and progression, but its mechanism is unclear. Krüppel-like factor 8 (KLF8) is a transcription factor that plays an important role in HCC progression. Here, we investigated the role of KLF8 in angiogenesis in HCC and its possible mechanism. Immunohistochemistry, quantitative RT-PCR, western blotting, promoter reporter assays, chromatin immunoprecipitation (ChIP), and chicken chorioallantoic membrane (CAM) and nude mouse tumor models were used to show that the mRNA and protein expression levels of KLF8 and VEGFA are highly correlated in HCC tissue samples. The up-regulation of KLF8 increased VEGFA protein levels and induced VEGFA promoter activity by binding to the CACCC region of the VEGFA promoter. In addition, KLF8 regulated HIF-1α and Focal adhesion kinase (FAK) expression. The PI3K/AKT inhibitor LY294002 inhibited KLF8-induced VEGFA expression, whereas PI3K/AKT signaling pathway proteins, such as P-PDK1(Ser241) and P-AKT(Thr308), were decreased significantly. KLF8-overexpressing HCC cells had a higher potential for inducing angiogenesis. Thus, our results indicate that KLF8 may induce angiogenesis in HCC by binding to the CACCC region of the VEGFA promoter to induce VEGFA promoter activity and through FAK to activate PI3K/AKT signaling to regulate HIF-1α expression levels.

Clinical study of 31 patients with primary gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: The purpose of the present paper was to investigate the clinical, endoscopic and histological features of 31 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to enable correct, early stage diagnosis. METHODS: A retrospective study was undertaken of 31 patients with gastric MALT lymphoma. The cases were examined immunohistologically with anti-CD(20CY) and CD(45RO) antibodies for further diagnosis. Helicobacter pylori infection was also detected with modified Giemsa staining. RESULTS: Patients with MALT lymphoma were aged between 22 and 73 years (mean, 45.0 years), and the male:female ratio was 11:20. The patients presented with non-specific symptoms, but chronic epigastric pain was the common symptom in a large proportion of the cases. The gastric smaller curvature was involved in 83.9% of cases (26/31) and in 13/31 cases (41.9%) it was confined the antrum. Under endoscopy, large and deep ulcers were similar to cancers in the majority of patients. Only 29.0% of patients were diagnosed by endoscopy on first examination. CD(20CY) were expressed in all cases and CD(45RO) expressed in only one case among 10 cases of indefinite diagnosis. Helicobacter pylori infection was found in 87.1% of patients. CONCLUSIONS: These findings suggest that primary gastric MALT lymphoma has unique clinical, endoscopic and histological features. The diagnosis for primary gastric MALT lymphoma was delayed not only due to the non-specific symptoms but also due to lack of attention to its features. Endoscopy and submucosal multiple biopsy were the principal diagnostic tools in patients with gastric MALT lymphoma. CD(20CY) and CD(45RO) immunological staining are recommended, especially for patients with indefinite diagnosis of gastric MALT lymphoma.