Highlights d Integrated analysis provides insight into the molecular classification in NKTCL d EBV lytic genes play an important role on NKTCL pathogenesis d Genomic alteration-based molecular subtypes associate with clinical outcomes d MYC, histone acetylation, and PD-L1/2 are potential therapeutic targets of NKTCL

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ObjectiveTo study the relationship between TRIM14 expression and chemotherapy resistance of gastric cancer (GC) cells.MethodsThe expression of TRIM14 in 5‐fluorouracil (5‐FU)‐ and oxaliplation (L‐OHP)‐resistant GC tissues and cells were determined by qRT‐PCR and western blotting. PcDNA3.1‐TRIM14 and shRNA‐TRIM14 vector were transfected to 5‐FU‐resistant GC cells (SGC7901/5‐FU), and the proliferation and apoptosis of cells were measured. Animal experiments on 5‐FU‐resistant GC mice were performed to study the effect of TRIM14 expression on tumor size and weight, GC cell migration, and proliferation. pcDNA3.1‐MK‐3903 plasmid was transfected to SGC7901/5‐FU cells with TRIM14 silence. The cell proliferation and apoptosis were determined. The protein expressions of Trim14, LC3, and BECLIN1 were measured by western blotting.ResultsTRIM14 was significantly upregulated in 5‐FU‐ and L‐OHP‐resistant GC tissues and cells. The overexpression of TRIM14 promoted the proliferation and autophagy of SGC7901/5‐FU cells, and inhibited the apoptosis. Moreover, in vivo experiment verified that the silence of TRIM14 reduced the tumor size and weight, and inhibited the migration and proliferation of GC cells in 5‐FU‐resistant GC mice. The overexpression of MK‐3903 reversed the inhibiting role of TRIM14 knockout on the proliferation and autophagy of SGC7901/5‐FU cells.ConclusionTRIM14 promoted chemotherapy resistance of GC cells by regulating AMPK/mTOR pathway, and may be a new biomarker for treating GC.

Clinicopathological and molecular features of indolent natural killer-cell lymphoproliferative disorder of the gastrointestinal tractAims: Indolent natural killer (NK) cell lymphoproliferative disorder of the gastrointestinal (GI) tract (iNKLPD) is a rare, recently recognised neoplasm. Most of the reported tumours are confined to the GI tract, while a small subset of the tumours harbour JAK3 mutations. We collected four cases of iNKLPD with the goal of adding additional information to the current knowledge of this disease regarding the clinicopathological, immunohistochemical and molecular features. Methods and results: Similar features including medium-to large-sized lymphoid cells with variable amounts of pale or slightly eosinophilic cytoplasm, and no evidence of EBER, TCR rearrangement were found in four cases. JAK3 K563_C565del mutation was found in one of three cases that were subjected to targeted next-generation sequencing. Unique findings of our study include one iNKLPD encountered for the first time in nasopharynx, where lesions could be inadvertently diagnosed as extranodal NK/T cell lymphoma, and one iNKLPD located in the gallbladder extended deeply into muscular and adventitial layers. Exceptional CD8-positive expression was observed in one iNKLPD. In addition, positive staining of phospho-STAT5, phospho-STAT3 and phospho-p38 were found in our cases. None of the four patients received therapy for lymphoma, but all had a benign clinical outcome during a follow-up time of 20-99 months. Conclusions: We present four iNKLPDs with clinical, immunohistochemical and molecular features similar to the reported cases, as well as some unusual characters, which expand our knowledge on this disease, and further support the neoplastic nature of iNKLPDs.