Frequent RNF43 mutation contributes to moderate activation of Wnt signaling in colorectal signet-ring cell carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC7093338 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Frequent RNF43 mutation contributes to moderate activation of Wnt signaling in colorectal signet-ring cell carcinoma.
Li Yaqi Y Li Jian J Wang Renjie R Zhang Long L Fu Guoxiang G Wang Xueying X Wang Yebin Y Fang Chuantao C Zhang Dandan D Du Duo D Ma Xiaoji X Pan Mengxue M Guo Qiang Q Xu Xiaoya X Hu Xiang X Zhou Yi Y Mo Shaobo S Wang Huijun H Gao Jianjun J Huang Shenglin S Liu Yun Y Cai Sanjun S Hua Guoqiang G Peng Junjie J Yu Fa-Xing FX
Protein & cell 20200401 4
Similar Datasets
Project description:Data used to look for gene expression changes correlating with DNA methylation in signet ring cell colorectal cancer.
2017-07-21 | GSE79793 | GEO
Project description:Identification of molecular subtypes of colorectal signet ring cell carcinoma based on differences in DNA methylation.
2017-07-21 | GSE79740 | GEO
Project description:BackgroundColorectal signet ring cell (SRC) carcinoma with ≥50% SRCs (SRC ≥ 50) has a poor prognosis, but the prognostic role of SRCs < 50% (SRC < 50) is unclear. The aim of this study was to provide a clinicopathological characterization of SRC colorectal and appendiceal tumours and analyse the importance of the SRC component size.MethodsAll patients in the Swedish Colorectal Cancer Registry diagnosed with colorectal or appendiceal cancer in 2009-2020 at Uppsala University Hospital, Sweden, were included. The SRCs were verified, and the components estimated by a gastrointestinal pathologist.ResultsOf the 2229 colorectal cancers, 51 (2.3%) had SRCs, with a median component size of 30% (interquartile range of 12.5-40) and 10 (0.45%) had SRC ≥ 50. The SRC tumours were primarily localized in the right colon (59%) and appendix (16%). No patients with SRCs had stage I disease, and 26 (51%) had stage IV, of whom, 18 (69%) had peritoneal metastases. The SRC tumours were often high grade with perineural and vascular invasion. The 5-year overall survival (OS) rate for patients with SRC ≥ 50 were 20% (95% confidence interval (CI) 6-70), for SRC < 50, 39% (95% CI 24-61); and for non-SRCs, 55% (95% CI 55-60). Among the patients with SRC < 50 and <50% extracellular mucin, the 5-year OS was 34% (95% CI 19-61), while those with ≥50% extracellular mucin had an OS of 50% (95% CI 25-99). The 5-year recurrence-free survival rates were 51% (95% CI 13-83) for patients with SRC tumours, as compared to 83% (95% CI 77-89) and 81% (95% CI 79-84) for mucinous and non-mucinous adenocarcinoma, respectively.ConclusionsThe presence of SRCs was strongly associated with aggressive clinicopathological features, peritoneal metastases, and poor prognosis, also when they make up <50% of a tumour.
| S-EPMC10177230 | biostudies-literature
Project description:BackgroundSignet-ring cell colorectal carcinoma (SRCC) is an extremely aggressive yet uncommon histologic subtype of colorectal cancer (CRC) with an unknown etiology. There is a stark difference in the prevalence of signet cancers between Western countries and the Indian subcontinent; however, India itself is a vast and diverse country with variable cancer incidence.ObjectiveTo study the spatial epidemiology of SRCC in India for identifying regions with high prevalence.MethodsThis retrospective study included all patients diagnosed with colorectal adenocarcinoma at Tata Memorial Hospital, the largest colorectal cancer referral unit in India, between January 2020 and December 2022. Geocoding based on the location of the residence was done to map the incidences. Comparisons were performed between the proportion of signet cell and non-signet colorectal cancers.ResultsA total of 4100 patients with colon or rectal adenocarcinomas were included, of which signet cell histology was found in 624 (15%) patients. SRCC accounted for the highest proportions of CRCs in the Central (19%) and Northern (19%) regions, and the lowest in the North-Eastern (10%) and Western (12%) regions of India (P < 0.001), with non-overlapping confidence intervals. Compared with patients with non-signet CRCs, those with SRCC more commonly had colon cancers (22% vs. 17%; P = 0.003) and belonged to a lower socioeconomic background (67% vs. 59%; P < 0.001).ConclusionsThis study found that SRCCs accounted for a significant proportion of CRC cases in India, but there was no substantial disparity in distribution across regions.
| S-EPMC10866387 | biostudies-literature
Project description:Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.
| S-EPMC6026495 | biostudies-literature
Project description:BackgroundSignet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC). The aim of this study was to characterise the genomic alterations and outcomes of SRCC.MethodsMedical records of metastatic CRC (mCRC) patients whose tumours were evaluated by NGS analysis were reviewed. SC-mCRC were classified into two groups: SRCC (>50% signet ring cells) and adenocarcinoma (AC) with SC component (≤50% signet ring cells).ResultsSix hundred and sixty-five mCRC patients were included. Of the 93 mCRC cases with SC features, 63 had slides for review. Of those 63 cases, 35 were confirmed SRCC, and 28 were AC with SC component. Compared with AC group, KRAS and PIK3CA mutations (mts) were found in only 11% (OR: 0.13) and 3% (OR: 0.15) of SRCC cases, respectively. In contrast to the 44% rate of APC mts in AC group, only 3% of SRCC patients had APC mts (OR = 0.04).ConclusionsSRCC has distinct molecular features, including low rates of KRAS, PIK3CA and APC mts. Further study to identify activation pathways and potential therapeutic targets are needed.
| S-EPMC6738104 | biostudies-literature
Project description:BackgroundWe performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.MethodsBetween November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.ResultsA slight male predominance was detected in these patients (59.0%). Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54) cases with KRAS mutations in 16.7% (9/54) cases and Nras mutations in 5.4%(3/54) cases. BRAF V600E mutation was detected in 3.7% (2/54) cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9%) cases were composed of ≥50% signet-ring cells; 22 (36.1%) cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences.ConclusionsColorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of signet-ring cells, regardless of the extent, shared similar clinicopathological characteristics, molecular alterations and genetic profiles.
| S-EPMC4907485 | biostudies-literature
Project description: Not available
| S-EPMC10695798 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-07-21 | GSE79794 | GEO
Project description:BackgroundColorectal signet ring cell carcinoma (SRCC) is a rare and poorly prognosed tumor with limited established prognostic indicators. This study aims to investigate the prognostic value of serum carcinoembryonic antigen (CEA) in patients with colorectal SRCC.MethodsA retrospective, multicenter study was conducted to assess the association between CEA levels and survival outcomes in 942 patients with colorectal SRCC.ResultsPatients exhibiting preoperative CEA (preCEA)-positivity demonstrated significantly lower cancer-specific survival (CSS) compared to those with preCEA-negativity in both Chinese and SEER datasets (5-year CSS: 27.50% vs. 48.27%, P = 0.01; 34.37% vs. 48.47%, P < 0.05). This disparity in outcomes was particularly notable in advanced stages (III, IV and N2; all P values < 0.05), while no statistical significance was observed in earlier stages (I/II, N0 and N1; all P values > 0.05). Patients with preCEA and postoperative CEA (postCEA)-negativity showed similar CSS to those with preCEA-positivity and postCEA-negativity, but those with postCEA-positivity had worse prognosis. After accounting for potential confounders, preCEA and postCEA maintained as independent predictors for CSS (P < 0.05). The nomogram model incorporating preCEA (preCEA-model) showed a C-index value of 0.75, whereas the model incorporating postCEA (postCEA-model) exhibited a C-index value of 0.73.ConclusionsBoth preoperative and postoperative elevation of CEA levels were associated with adverse outcomes, with preoperative CEA demonstrating particularly significant predictive value in advanced-stage tumors. These findings propose that CEA could be a valuable tool for dynamically monitoring the prognosis of colorectal SRCC patients.
| S-EPMC11913837 | biostudies-literature