“…Diagnosis at advanced stages is one of the determinants of the disparity in survival and a large number of CRC deaths worldwide. Thus, population-based screening programs have been widely proposed and implemented in some highly developed countries since more than 10 years ago, with the aim of shifting CRC distribution to early stages and improving therapy outcomes [ 3 , 17 , 18 ]. Fig.…”
Highlights
There are estimated 1.93 million new CRC cases diagnosed, and 0.94 million CRC caused deaths in 2020 worldwide.
The global new CRC cases is predicted to reach 3.2 million in 2040.
China and the United States have the highest estimated number of new CRC cases in the next 20 years.
The number of new CRC cases is increased from 0.56 million (2020) to 0.91 million (2040) in China.
The number of new CRC cases is increased from 0.16 million (2020) to 0.21 million (2040) in the United States.
“…Diagnosis at advanced stages is one of the determinants of the disparity in survival and a large number of CRC deaths worldwide. Thus, population-based screening programs have been widely proposed and implemented in some highly developed countries since more than 10 years ago, with the aim of shifting CRC distribution to early stages and improving therapy outcomes [ 3 , 17 , 18 ]. Fig.…”
Highlights
There are estimated 1.93 million new CRC cases diagnosed, and 0.94 million CRC caused deaths in 2020 worldwide.
The global new CRC cases is predicted to reach 3.2 million in 2040.
China and the United States have the highest estimated number of new CRC cases in the next 20 years.
The number of new CRC cases is increased from 0.56 million (2020) to 0.91 million (2040) in China.
The number of new CRC cases is increased from 0.16 million (2020) to 0.21 million (2040) in the United States.
“…The PAPSS2 gene encodes 3′-phosphoadenosine 5′-phosphosulfate synthase 2, which is involved in several biological processes, 30 including the sulfation conjugation of xenobiotic compounds. 31 PAPSS2 has been reported to be expressed at low levels in prostate cancer 32 and colon cancer 33 tissues. PCOLCE2 promotes the enzymatic cleavage of type-I procollagen to yield mature, structured fibrils.…”
Purpose
Although well-differentiated papillary thyroid carcinoma (PTC) has an indolent nature and usually an excellent prognosis, some patients experience disease recurrence or death. The aim of this study was to identify prognostic markers to stratify PTC patients.
Patients and Methods
Eight gene-expression profiles (GSE3467, GSE3678, GSE5364, GSE27155, GSE33630, GSE53157, GSE60542, and GSE104005) were obtained from the Gene Expression Omnibus and used to analyze differentially expressed genes (DEGs) between PTC tissues and non-tumor tissues. Univariable Cox regression survival analysis and Lasso-penalized Cox regression analysis were performed to identify prognostic genes and establish a risk-score model based on the integrated DEGs. Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves were used to validate the prognostic performance of the risk score. A nomogram was constructed based on The Cancer Genome Atlas dataset and Multivariable Cox regression analysis.
Results
A total of 165 upregulated and 207 downregulated DEGs were screened. A four-gene signature including PAPSS2, PCOLCE2, PTX3, and TGFBR3 was identified. The risk-score model showed a strong diagnosis performance for identifying patients with a poor prognosis. KM analysis showed that patients with low risk scores had a significantly more favorable overall survival (OS) than those with high risk scores (p = 0.0002). ROC curves based on the four-gene signature showed better performances in predicting 1-, 3-, and 5-year survival than did the American Joint Committee on Cancer staging system (area under the curve: 0.86 vs 0.84, 0.80 vs 0.63, and 0.79 vs 0.73, respectively). Furthermore, when combined with age and tumor status from the nomogram, the four-gene signature achieved a good performance in guiding postoperative follow-up surveillance of patients with PTC.
Conclusion
The four-gene signature was found to be a novel and reliable biomarker with great potential for clinical application in risk stratification and OS prediction in patients with PTC.
“…Like all glycan modifications, sulfation requires a donor, in this case 3′-phosphoadenosine-5′-phosphosulfate (PAPS), for enzymatic sulfation. Recently, using a conditional genetic strategy to delete the enzyme PAPS Synthase 2 (PAPSS2) in gut epithelium, which promotes donor synthesis, it was demonstrated that sulfation defects in epithelial cells led to enhanced sensitivity to colitis and lumen-to-systemic spread of the colon microbiota, 96 suggesting a more generalized tolerance strategy of sulfation toward the microbiota. However, PAPS loss in epithelium also affected sulfation of bile acids, so the relative impact of mucin-type O-glycans and other sulfated molecules is still unclear.…”
Section: O-glycans In Relation To Muc2-dependent Tolerance-mediated D...mentioning
confidence: 99%
“…However, PAPS loss in epithelium also affected sulfation of bile acids, so the relative impact of mucin-type O-glycans and other sulfated molecules is still unclear. 96 …”
Section: O-glycans In Relation To Muc2-dependent Tolerance-mediated D...mentioning
Over the past two decades, our appreciation of the gut mucus has moved from a static lubricant to a dynamic and essential component of the gut ecosystem that not only mediates the interface between host tissues and vast microbiota, but regulates how this ecosystem functions to promote mutualistic symbioses and protect from microbe-driven diseases. By delving into the complex chemistry and biology of the mucus, combined with innovative in vivo and ex vivo approaches, recent studies have revealed novel insights into the formation and function of the mucus system, the O-glycans that make up this system, and how they mediate two major host-defense strategies – resistance and tolerance – to reduce damage caused by indigenous microbes and opportunistic pathogens. This current review summarizes these findings by highlighting the emerging roles of mucus and mucin-type O-glycans in influencing host and microbial physiology with an emphasis on host defense strategies against bacteria in the gastrointestinal tract.
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