duodenal-jejunal-bypass-surgery-in-diet-induced-obese-diabetic-mice

Duodenal-Jejunal Bypass Surgery in Diet-Induced Obese Diabetic Mice

The prevalence of obesity and type 2 diabetes is a serious global health concern. Obesity is a major pathogenic factor in type 2 diabetes, cardiovascular ...

General Hospital of Southern Theatre Command

Although microRNAs offer great potential as cancer biomarkers, effective clinical dignostics and tumor maker have not been verified to diagnose with colorectal cancer (CRC). The purpose of our study is to systematically assess the expression of miRNAs in matched cancer and normal tissue samples to identify promising diagnostic microRNA (miRNA) biomarkers for CRC.

Paired design study by real-time PCR: miR-378* and miR-145 are potent early diagnostic biomarkers of human colorectal cancer.

 Bowel cancer is the third-most common cancer and the second leading cause of cancer-related death worldwide. Bowel cancer has a substantial hereditary component; however, additional hereditary risk factors involved in bowel cancer pathogenesis have not been systematically defined.  A total of 573 patients with bowel cancer were enrolled in the present study, of whom 93.72% had colorectal cancer (CRC). Germline mutations were integrated with somatic mutation information via utilizing target next-generation sequencing.  Pathogenic/Likely Pathogenic (P/LP) germline alterations were identified in 47 (8.2%) patients with bowel cancer and the ratio of the number of these patients with family history was significantly higher in the P/LP group than that noted in the non-pathogenic (Non-P) group. Certain rare germline alterations were noted, such as those noted in the following genes: , and . A total of 32 patients (68.1%) had germline alterations in the DNA-damage repair (DDR) genes and homologous recombination (HR) accounted for the highest proportion of this subgroup. By comparing 573 patients with bowel cancer with reference controls (China_MAPs database), significant associations ( < 0.01) were observed between the incidence of bowel cancer and the presence of mutations in , and . Somatic gene differential analysis revealed a marked difference in 18 genes and a significant difference was also noted in tumor mutation burden (TMB) between germline mutation carriers and non-germline mutation subjects ( < 0.001). In addition, TMB in DDR mutation groups indicated a dramatic difference compared with the non-DDR mutation group ( < 0.01). However, no statistically significant differences in TMB were noted among detailed DDR pathways for patients with bowel cancer, irrespective of the presence of germline mutations. Moreover, a significantly higher level ( < 0.0001) of mutation count was observed in the DDR group from The Cancer Genome Atlas (TCGA) database and the DDR and non-DDR alteration groups displayed various immune profiles.  Chinese patients with bowel cancer exhibited a distinct spectrum of germline variants, with distinct molecular characteristics such as TMB and DDR. Furthermore, the information on somatic mutations obtained from TCGA database indicated that a deeper understanding of the interactions among DDR and immune cells would be useful to further investigate the role of DDR in bowel cancer.

Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer.

Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26-bearing mice model was established to examine GRIK5-induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer.

GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling.

The clinicopathological risk factors in the prognosis of stage IV gastric cancer have been comprehensively studied. However, the influencing factors of stage IV gastric cancer prognosis at genomic and transcriptional levels have not been well defined.

Article	Year
Paired design study by real-time PCR: miR-378* and miR-145 are potent early diagnostic biomarkers of human colorectal cancer. BMC cancer\| PubMed ID: 25896668	2015
Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer. Frontiers in genetics\| PubMed ID: 35154239	2021
GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling. Cell biology international\| PubMed ID: 36959746	2023
Mutational and transcriptional profile predicts the prognosis of stage IV gastric cancer - Prognostic factors for metastatic gastric cancer. Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology\| PubMed ID: 39043541	2024

Zhengyong Xie

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