Management of type 1 gastric neuroendocrine tumors: an 11-year retrospective single-center study.

BACKGROUND: Type 1 gastric neuroendocrine tumors (NETs) are relatively rare to the extent that some physicians have little experience in diagnosing and treating them. The purpose of this study was to increase the understanding of the disease by analyzing and summarizing the management and prognoses of patients with type 1 gastric NETs at our center. METHODS: The data of 229 patients (59.4% female) with type 1 gastric NETs who were treated at our center during 2011-2022 were retrospectively analyzed. RESULTS: The average patient age was 50.5 ± 10.8 years. Multiple tumors affected 72.5% of the patients; 66.4% of the tumors were < 1 cm, 69.4% were NET G1, and 2.2% were stage III-IV. A total of 76.9% of the patients had received endoscopic management, 60.7% had received traditional Chinese medicine treatment, 10.5% received somatostatin analogues treatment, and 6.6% underwent surgical resection. Seventy patients (41.2%) experienced the first recurrence after a median follow-up of 31 months (range: 2-122 months), and the median recurrence-free time was 43 months. The 1-, 2-, and 3-year cumulative recurrence-free survival rates were 71.8%, 56.8%, and 50.3%, respectively. During a median follow-up of 39 months (range: 2-132 months), one patient had bilateral pulmonary metastasis, and no disease-related deaths were observed. CONCLUSION: Type 1 gastric NETs have a high recurrence rate and a long disease course, underscoring the importance of long-term and comprehensive management.

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing.

BACKGROUND: The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood. METHODS: Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated. RESULTS: The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (- 65 to - 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10). CONCLUSION: These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.

Screening key long non-coding RNAs in early-stage colon adenocarcinoma by RNA-sequencing.

AIM: We aim to identify the key long noncoding RNAs (lncRNAs) in early-stage colon adenocarcinoma (COAD). PATIENTS & METHODS: Compared with colonic intraepithelial neoplasia, differentially expressed lncRNAs (DElncRNAs) in early-stage COAD were obtained by RNA-sequencing. Our previous work has obtained the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs) in early-stage COAD. DEmiRNA-DElncRNA-DEmRNA interaction analysis and functional annotation were performed. Validation of expression and receiver-operating characteristic analyses were performed based on The Cancer Genome Atlas. RESULTS: Seventy-nine significantly DElncRNAs in early-stage COAD were obtained. MiR-153-3p-TUG1-DAPK1/ARNT2/KLK3/PLD1/SMAD2 and miR-153-3p-SNHG17-COL11A1/IGFBP3/KLF6 interactions were associated with early-stage COAD. Five DElncRNAs (ELFN1-AS1, LINC01234, SNHG17, UCA1 and LOC101929549) involved in early-stage COAD with potential diagnostic value. CONCLUSION: LncRNAs involve in early-stage COAD by interaction with COAD-regulated genes and miRNAs.

Hsa-miR-202-3p, up-regulated in type 1 gastric neuroendocrine neoplasms, may target DUSP1.

AIM: To detect abnormal microRNA (miRNA) expression in type 1 gastric neuroendocrine neoplasms (g-NENs) and find potential target genes. METHODS: Tumour tissues from patients with type 1 g-NENs were used as experimental samples, and gastric mucosal tissues from the same patients obtained during gastroscopy review after several months were used as control samples. miRNA expression was examined with Agilent human miRNA chips and validated via RT-PCR. Three types of target gene prediction software (TargetScan, PITA, and microRNAorg) were used to predict potential target genes of the differentially expressed miRNAs, and a dual-luciferase reporter assay system was used for verification. RESULTS: Six miRNAs were significantly upregulated or downregulated in the tumours compared to the control samples. Among them, miR-202-3p was extraordinarily upregulated. RT-PCR of seven sample sets confirmed that miR-202-3p was upregulated in tumour tissues. In total, 215 target genes were predicted to be associated with miR-202-3p. Among them, dual-specificity phosphatase 1 (DUSP1) was reported to be closely related to tumour occurrence and development. The dual-luciferase reporter assay showed that miR-202-3p directly regulated DUSP1 in 293T cells. CONCLUSION: miR-202-3p is upregulated in type 1 g-NEN lesions and might play important roles in the pathogenesis of type 1 g-NENs by targeting DUSP1.

Associations of adiponectin receptor 2 (AdipoR2) gene polymorphisms and AdipoR2 protein expression levels with the risk of colorectal cancer: A case-control study.

The aim of the present study was to investigate the associations between adiponectin receptor 2 (AdipoR2) gene polymorphisms, AdipoR2 protein expression levels and the risk of colorectal cancer (CRC). From April 2012 to May 2015, 281 CRC patients (case group) admitted to the China­Japan Friendship Hospital and 325 healthy control subjects (control group) were recruited for the study. Peripheral venous blood samples were collected and the DNA was extracted. Genotyping was performed using denaturing high­performance liquid chromatography in the condition of partial degeneration. Linkage disequilibrium and haplotype were analyzed using SHEsis analysis software. AdipoR2 protein expression levels were detected by immunohistochemistry and logistic regression analysis was performed to determine the risk factors of CRC. The distribution of the TT genotype of AdipoR2 rs10773989 and the CC genotype of AdipoR2 rs1044471 was higher in the case group than in the control group (P<0.05). The AdipoR2 rs10773989 polymorphism was associated with the degree of tumor infiltration in CRC (P<0.05) and the AdipoR2 rs1044471 polymorphism was associated with the degree of differentiation and Dukes' staging in CRC (P<0.05). The CT haplotype was identified as a protective factor, while the TC haplotype was a risk factor in a healthy population. AdipoR2 protein expression was associated with the degree of differentiation, Dukes' staging, degree of tumor infiltration and lymphatic metastasis in CRC (all P<0.05). Logistic regression analysis demonstrated that the TT genotype of AdipoR2 rs10773989 and CC genotype of AdipoR2 rs1044471 were independent risk factors for CRC. The AdipoR2 rs10773989 and rs1044471 polymorphisms may be correlated with the susceptibility to CRC. In addition, the TC haplotype and AdipoR2 positive expression may increase the risk of CRC.