Primary malignant melanoma of the gastroesophageal junction with KIT gene exon 11 mutation.

Mucosal melanoma (MM) represents an uncommon form of melanoma. Primary gastrointestinal tract (GIT) melanoma is even rarer. A 70-year-old male visited the Liaoning Cancer Hospital and Institute, China, due to upper abdominal discomfort for the past two months. His endoscopy revealed a prominent, 6-cm ulcerated neoplasm in the gastroesophageal junction (GEJ). Lesion endoscopic biopsy showed diffusely distributed tumour cells. He underwent subtotal gastrectomy with lymph node dissection (LND). Postoperative histopathology revealed a diffuse distribution of tumour cells with numerous tumourinfiltrating lymphocytes (TILs) and pigment granules. Immunohistochemical (IHC) results were positive for both S-100 and HMB-45. Molecular analysis showed KIT gene exon 11 mutations. Although the clinicians emphasised the necessity of systemic chemotherapy and immunotherapy with the patient and his family, the patient did not receive any adjuvant therapy and died 36 months after surgery. Primary malignant melanoma of GEJ should be considered in a differential diagnosis for gastrointestinal malignancies, especially after excluding the source of metastasis through a systemic examination.

LncRNA NEAT1 promotes proliferation, migration, and invasion of laryngeal squamous cell carcinoma cells through miR-411-3p/FZD3-mediated Wnt signaling pathway.

The lncRNA NEAT1 has been shown to promote the progression of several cancers, containing laryngeal squamous cell carcinoma (LSCC). However, the precise mechanism by which it promotes LSCC progression remains unclear. In this study, we verified the high expression of lncRNA NEAT1 in LSCC tissues and cells using RT-qPCR. Analysis of clinical data exhibited that high expression of lncRNA NEAT1 was associated with a history of smoking, worse T stage, lymph node metastasis, and later TNM stage in patients with LSCC. The promotion effect of lncRNA NEAT1 on LSCC cell proliferation, migration, invasion, and tumor growth in vivo was verified by CCK-8, plate clone formation, Transwell, and nude mouse tumorigenicity assays. Bioinformatics prediction and double luciferase reporter gene assay verified the binding of miR-411-3p to lncRNA NEAT1 and FZD3 mRNA, and inhibition of miR-411-3p reversed the inhibitory effect of lncRNA NEAT1 on FZD3 expression in LSCC cells. We also verified that lncRNA NEAT1-mediated FZD3 activation in the Wnt pathway affects LSCC development. In conclusion, we demonstrate that lncRNA NEAT1 promotes the progression of LSCC, and propose that the lncRNA NEAT1/miR-411-3p/FZD3 axis may be an effective target for LSCC therapy.

Role of pathological tumor regression grade of lymph node metastasis following neoadjuvant chemotherapy in locally advanced gastric cancer.

AIMS: To confirm whether the pathological response of lymph node metastasis (LNM) to neoadjuvant chemotherapy (NCT) can predict the prognosis of patients with gastric cancer (GC). METHODS: A total of 979 patients with locally advanced GC were included. χ2 test was used to analyze the relationship between LNM TRG and clinicopathological factors. Cox proportional hazards model was used to analyze the relationship between LNM TRG, clinicopathological factors, and overall survival (OS). RESULTS: A total of 21,162 lymph nodes were evaluated, with 237 patients (35.4%) in the response group and 433 patients (64.6%) in the non-response group. The non-responsive group was strongly associated with higher ypT, ypN, ypTNM, primary tumor (PT) TRG (all p < 0.001), positive cancer nodules (p = 0.001), and more distant LNM location (p < 0.001). Patients with the same PT TRG but different LNM TRG had different prognosis. There was no difference in OS between the responding and non-responding groups of LNM at location 2, 3, and M. YpN, tumor location, and LNM location were independent prognostic factors. CONCLUSIONS: The combination of LNM TRG and PT TRG could better predict patient prognosis. Lymph node dissection should be routinely performed after NCT to provide the reference of radical resection.

Extracellular vesicles: A new diagnostic biomarker and targeted drug in osteosarcoma.

Osteosarcoma (OS) is a primary bone cancer that is highly prevalent among adolescents and adults below the age of 20 years. The prognostic outcome of metastatic OS or relapse is extremely poor; thus, developing new diagnostic and therapeutic strategies for treating OS is necessary. Extracellular vesicles (EVs) ranging from 30-150 nm in diameter are commonly produced in different cells and are found in various types of body fluids. EVs are rich in biologically active components like proteins, lipids, and nucleic acids. They also strongly affect pathophysiological processes by modulating the intercellular signaling pathways and the exchange of biomolecules. Many studies have found that EVs influence the occurrence, development, and metastasis of osteosarcoma. The regulation of inflammatory communication pathways by EVs affects OS and other bone-related pathological conditions, such as osteoarthritis and rheumatoid arthritis. In this study, we reviewed the latest findings related to diagnosis, prognosis prediction, and the development of treatment strategies for OS from the perspective of EVs.

LINC00261 inhibits progression of pancreatic cancer by down-regulating miR-23a-3p.

Long noncoding RNAs (lncRNAs) are usually dysregulated in the progression of pancreatic cancer. This research aims to explore the function and mechanism of LINC00261 in pancreatic cancer cell viability, invasion and apoptosis. Cancer Genome Atlas (TCGA) database was applied to analyze the association between survival probability of patients and level of LINC00261 or miR-23a-3p in pancreatic cancer. Quantitative reverse transcription polymerase chain reaction was conducted to analyze the levels of LINC00261 and miR-23a-3p. Cell viability, invasion and apoptosis of pancreatic cancer cells were determined via MTT, transwell invasion assay, and flow cytometry, respectively. The target relationship between LINC00261 and miR-23a-3p was determined via dual-luciferase reporter and RNA immunoprecipitation assays. Low level of LINC00261 indicated low survival probability of pancreatic cancer patients. LINC00261 level was decreased in pancreatic cancer cells than that in normal pancreatic ductal epithelial cells. Addition of LINC00261 restrained cell viability and invasion and facilitated apoptosis. miR-23a-3p was negatively correlated with LINC00261 level and high expression of miR-23a-3p indicated low survival probability. miR-23a-3p was targeted by LINC00261 and attenuated the influence of LINC00261 on pancreatic cancer cell viability, invasion and apoptosis. In conclusion, LINC00261 overexpression repressed cell viability and invasion and enhanced apoptosis by decreasing miR-23a-3p expression in pancreatic cancer cells, indicating a new target for the treatment of pancreatic cancer.

C14orf159 suppresses gastric cancer cells' invasion and proliferation by inactivating ERK signaling.

BACKGROUND: C14orf159, a new protein, has been identified recently. But its expression in tissues and clinicopathologic correlation is still unknown. PATIENTS AND METHODS: We carried out immunohistochemistry staining in 144 gastric cancer cases in this study. Then Western blot was used to detect the expression of protein. MTT and matrigel invasion assay were used to assess the biological effects. RESULTS: The immunohistochemical results indicated that the expression of C14orf159 in normal gastric mucosa close to cancer tissue was remarkably higher than that in stomach carcinoma samples (63.9% and 34.7%, respectively, P<0.001). Negative C14orf159 expression was dramatically related to high TNM stages (P=0.033) and positive lymph node metastasis (P=0.008). Once C14orf159 was overexpressed, the expression levels of phosphorylated ERK and its regulated downstream molecules, such as Snail, phosphorylated P90RSK and Cyclin D1, were decreased, while the expression level of E-cadherin was increased. Finally, the invasion and proliferation capacity of gastric cancer cells was inhibited. CONCLUSION: In other words, loss of C14orf159 is associated with the progression of gastric cancer. The role of C14orf159 in repression of proliferation and invasion may be due to resuming E-cadherin and abolishing Snail and Cyclin D1 expression through inactivating ERK-P90RSK pathway.