GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

Lin, Wey‐Ran; Chiang, Jy-Ming; Liang, Kung–Hao; Lim, Siew‐Na; Lai, Ming‐Wei; Tsou, Yung-Kuan; Hsieh, Tzu-Yun; Hsu, Chih-Kai; Yeh, Chau‐Ting

doi:10.1097/md.0000000000003487

Cited by 14 publications

(17 citation statements)

References 25 publications

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“…We selected 5 types of ppGalNac-Ts (GALNT2, GALNT3, GALNT6, GALNT12, GALNT14), as these ppGalNac-Ts have been reported to be closely associated with CRC. [27][28][29][30][31] Our analysis did not detect obvious differences in the mRNA levels of these ppGalNAc-Ts between Cosmc-overexpressing cells and the control cells ( Figure 4C). Collectively, these results suggested that aberrant O-glycosylation is unlikely the cause for Cosmc overexpression-mediated oncogenic alterations.…”

Section: Cosmc Overexpression-mediated Oncogenic Alterations Were Nmentioning

confidence: 65%

Cosmc overexpression enhances malignancies in human colon cancer

Gao

et al. 2019

J Cellular Molecular Medi

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Cosmc is known as a T‐synthase‐specific molecular chaperone that plays a crucial role in the process of O‐glycosylation. Cosmc dysfunction leads to inactive T‐synthase and results in aberrant O‐glycosylation, which is associated with various tumour malignancies. However, it is unclear whether Cosmc has some other functions beyond its involvement in O‐glycosylation. In this study, we aimed to investigate the functional role of Cosmc in human colorectal cancer (CRC). We first assessed the expression levels of Cosmc in human CRC specimens and then forcedly expressed Cosmc in human CRC cell lines (HCT116, SW480) to examine its impact on cellular behaviours. The mechanisms for aberrant expression of Cosmc in CRC tissues and the altered behaviours of tumour cells were explored. It showed that the mRNA and protein levels of Cosmc were markedly elevated in human CRC specimens relative to normal colorectal tissues. The occurrence of endoplasmic reticulum (ER) stress may largely contribute to the increased Cosmc expression in cancer tissue and cells. Cosmc overexpression in CRC cells significantly promoted cell migration and invasion, which could be attributed to the activation of the epithelial‐mesenchymal transition (EMT) pathway rather than aberrant O‐glycosylation. These data indicate that Cosmc expression was elevated in human CRC possibly caused by ER stress, which further enhanced malignancies through the activation of EMT but independently of aberrant O‐glycosylation.

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Section: Cosmc Overexpression-mediated Oncogenic Alterations Were Nmentioning

confidence: 65%

Cosmc overexpression enhances malignancies in human colon cancer

Gao

et al. 2019

J Cellular Molecular Medi

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“…The intragenic heterozygous deletion in GALNT14 identified in patient 1 was inherited from a healthy father and as GALNT14 has not previously been implicated in human disease, the deletion was considered as of uncertain significance. GALNT14 is important during embryonal development, and its relevance in cancer and cancer therapy is being investigated (Lin et al, 2016;Mariano et al, 2015;Tsou et al, 2017). GALNT14 overexpression increases mRNA expression of N-cadherin (Huanna et al, 2015), which is a cell adhesion protein with an important role in asymmetric cell-formations in the dorsal mesentery (Davis et al, 2008;Plageman, Zacharias, Gage, & Lang, 2011;Welsh et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation

Karlslätt

Pettersson

Jäntti

et al. 2019

Molec Gen & Gen Med

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Background Intestinal malrotation is a potentially life‐threatening congenital anomaly due to the risk of developing midgut volvulus. The reported incidence is 0.2%–1% and both apparently hereditary and sporadic cases have been reported. Intestinal malrotation is associated with a few syndromes with known genotype but the genetic contribution in isolated intestinal malrotation has not yet been reported. Rare copy number variants (CNVs) have been implicated in many congenital anomalies, and hence we sought to investigate the potential contribution of rare CNVs in intestinal malrotation. Methods Analysis of array comparative genomic hybridization (aCGH) data from 47 patients with symptomatic intestinal malrotation was performed. Results We identified six rare CNVs in five patients. Five CNVs involved syndrome loci: 7q11.23 microduplication, 16p13.11 microduplication, 18q terminal deletion, HDAC8 (Cornelia de Lange syndrome type 5 and FOXF1 ) as well as one intragenic deletion in GALNT14 , not previously implicated in human disease. Conclusion In the present study, we identified rare CNVs contributing pathogenic or potentially pathogenic alleles in five patients with syndromic intestinal malrotation, suggesting that CNV screening is indicated in intestinal malrotation with associated malformations or neurological involvements. In addition, we identified intestinal malrotation in two known syndromes (Cornelia de Lange type 5 and 18q terminal deletion syndrome) that has not previously been associated with gastrointestinal malformations.

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“…Although adjuvant chemotherapy has been shown to reduce around 30% of disease recurrence and 22% to 32% of mortality, not all patients benefit from adjuvant therapy [30][31][32]. Therefore, the predictive role of the GALNT14-rs9679162 SNP was investigated in this group of patients [33]. A cohort of 300 patients with stage III colorectal adenocarcinoma receiving curative resection followed by oxaliplatin-based chemotherapy was retrospectively recruited.…”

Section: Colorectal Adenocarcinomamentioning

confidence: 99%

GALNT14: An Emerging Marker Capable of Predicting Therapeutic Outcomes in Multiple Cancers

Lin

Yeh

2020

IJMS

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Members of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family function as the initiating enzymes that catalyze mucin-type O-glycosylation of proteins, and their dysregulated expression can alter cancer cell behaviors such as de novo occurrence, proliferation, migration, metastasis, and drug resistance. Recent studies have demonstrated that one of the family’s members, GALNT14, is aberrantly expressed in multiple cancers and involved in a variety of biological functions. Moreover, the single nucleotide polymorphisms (SNPs) of GALNT14-rs9679162 have been shown to predict therapeutic outcomes in patients with hepatocellular carcinoma as well as several other different types of gastrointestinal cancer. This review summarizes the structural features of GANLT14, its functional roles, and the predictive values of GALNT14 genotypes and enzyme levels in multiple cancers receiving distinct anticancer therapies.

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GALNT14 Genotype Predicts Postoperative Outcome of Stage III Colorectal Cancer With Oxaliplatin as Adjuvant Chemotherapy

Abstract: Supplemental Digital Content is available in the text

Cited by 14 publications

References 25 publications

Cosmc overexpression enhances malignancies in human colon cancer

Cosmc overexpression enhances malignancies in human colon cancer

Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation

GALNT14: An Emerging Marker Capable of Predicting Therapeutic Outcomes in Multiple Cancers

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