Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis

BACKGROUND Proteomic signatures of Ming's infiltrative gastric cancer(IGC)remain unknown.AIM To elucidate the molecular characteristics of IGC at the proteomics level.METHODS Twelve pairs of IGC and adjacent normal tissues were collected and their proteomes were analyzed by high performance liquid chromatography tandem mass spectrometry.The identified peptides were sequenced de novo and matched against the SwissProt database using Maxquant software.The differentially expressed proteins(DEPs)were screened using|log2(Fold change)|>1 and P-adj<0.01 as the thresholds.The expression levels of selected proteins were verified by Western blotting.The interaction network of the DEPs was constructed with the STRING database and visualized using Cytoscape with cytoHubba software.The DEPs were functionally annotated using clusterProfiler,STRING and DAVID for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways.P<0.05 was considered statistically significant.RESULTS A total of 7361 DEPs were identified,of which 94 were significantly up-regulated and 223 were significantly down-regulated in IGC relative to normal gastric tissues.The top 10 up-regulated proteins were MRTO4,BOP1,PES1,WDR12,BRIX1,NOP2,POLR1C,NOC2L,MYBBP1A and TSR1,and the top 10 down-regulated proteins were NDUFS8,NDUFS6,NDUFA8,NDUFA5,NDUFC2,NDUFB8,NDUFB5,NDUFB9,UQCRC2 and UQCRC1.The up-regulated proteins were enriched for 9 biological processes including DNA replication,ribosome biogenesis and initiation of DNA replication,and the cellular component MCM complex.Among the down-regulated proteins,17 biological processes were enriched,including glucose metabolism,pyruvic acid metabolism and fatty acidβ-oxidation.In addition,the mitochondrial inner membrane,mitochondrial matrix and mitochondrial proton transport ATP synthase complex were among the 6 enriched cellular components,and 11 molecular functions including reduced nicotinamide adenine dinucleotide dehydrogenase activity,acyl-CoA dehydrogenase activity and nicotinamide adenine dinucleotide binding were also enriched.The significant KEGG pathways for the up-regulated proteins were DNA replication,cell cycle and mismatch repair,whereas 18 pathways including oxidative phosphorylation,fatty acid degradation and phenylalanine metabolism were significantly enriched among the down-regulated proteins.CONCLUSION The proteins involved in cell cycle regulation,DNA replication and mismatch repair,and metabolism were significantly altered in IGC,and the proteomic profile may enable the discovery of novel biomarkers.

Microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence

AIM: To investigate the microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence. METHODS: Forty-one specimens were obtained from esophageal cancer (EC) patients. Histopathological assessment identified 23 squamous cell carcinomas (SCC) and 18 adenocarcinomas (ADC), including only 8 ADC with Barrett esophageal columnar epithelium (metaplasia) and dysplasia adjacent to ADC. Paraffin-embedded normal squamous epithelium, Barrett esophageal columnar epithelium (metaplasia), dysplasia and esophageal tumor tissues were dissected from the surrounding tissues under microscopic guidance. DNA was extracted using proteinase K digestion buffer, and DNA was diluted at 1:100, 1:1000, 1:5000, 1:10 000 and 1:50 000, respectively. Seven microsatellite markers (D2S123, D3S1616, D3S1300, D5S346, D17S787, D18S58 and BATRII loci) were used in this study. Un-dilution and dilution polymerase chainreactions (PCR) were performed, and microsatellite analysis was carried out. RESULTS: No statistically significant difference was found in microsatellite instability (MSI) and loss of heterozygosity (LOH) of un-diluted DNA between SCC and ADC. The levels of MSI and LOH were high in the metaplasia-dysplasia-adenocarcinoma sequence of diluted DNA. The more the diluted DNA was, the higher the rates of MSI and LOH were at the above 7 loci, especially at D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci. CONCLUSION: The sequence of metaplasia-dysplasia-adenocarcinoma is associated with microsatellite alterations, including MSI and LOH. The MSI and LOH may be the early genetic events during esophageal carcinogenesis, and genetic alterations at the D3S1616, D5S346 and D3S123 loci may play a role in the progress of microsatellite alterations.

International consensus on natural orifice specimen extraction surgery(NOSES)for colorectal cancer

In recent years,natural orifice specimen extraction surgery(NOSES)in the treatment of colorectal cancer has attracted widespread attention.The potential benefits of NOSES including reduction in postoperative pain and wound complications,less use of postoperative analgesic,faster recovery of bowel function,shorter length of hospital stay,better cosmetic and psychological effect have been described in colorectal surgery.Despite significant decrease in surgical trauma of NOSES have been observed,the potential pitfalls of this technique have been demonstrated.Particularly,several issues including bacteriological concerns,oncological outcomes and patient selection are raised with this new technique.Therefore,it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery.After three rounds of discussion by all members of the International Alliance of NOSES,the consensus is finally completed,which is also of great significance to the long-term progress of NOSES worldwide.

International consensus on natural orifice specimen extraction surgery(NOSES)for gastric cancer(2019)

At present,natural orifice specimen extraction surgery(NOSES)has attracted more and more attention worldwide,because of its great advantages including minimal cutaneous trauma and post-operative pain,fast post-operative recovery,short hospital stay,and positive psychological impact.However,NOSES for the treatment of gastric cancer(GC)is still in its infancy,and there is great potential to improve its theoretical system and clinical practice.Especially,several key points including oncological outcomes,bacteriological concerns,indication selection,and standardized surgical procedures are raised with this innovative technique.Therefore,it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES,which is of great significance for healthy and orderly development of NOSES worldwide.