Investigation of clinicopathological characters and gene expression features in colorectal signet-ring cell carcinoma
Kensuke Tajiri1,2, Tomoya Sudo1,2, Kazuo Ishi3
1Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan.
Abstract:
Signet ring cell carcinoma (SRCC) is a rare pathological type of colorectal cancer, of which the clinicopathological features and genetic background have not yet been fully investigated. Previous research has focused on the optimization of colorectal cancer treatment utilizing consensus molecular subtyping (CMS). However, it is not known what type of CMS would be designated to SRCC treatment. In the current study, of 1,350 patients diagnosed with colorectal cancer who underwent surgery, 14 were diagnosed with SRCC. The case-control cohort that fit the clinical background of the SRCC case was constructed. Statistical comparison between the SRCC group and the case-control cohort was performed among clinicopathological variables. SRCC and well to moderately adenocarcinoma case mRNA were submitted to microarray analysis and CMS analysis. Compared with the case-control cohort, the SRCC group was located more in the right-sided colon, the lymphatic invasion was more severe and the peritoneal dissemination was more frequent. The cancer-specific survival and the progression-free survival were significantly worse in the SRCC group compared with the case-control cohort. Microarray and CMS analysis identified that one SRCC case was significantly well assigned in the CMS 4 group and the other case was assigned in the CMS 1 group. Gene set analysis revealed the upregulation of EMT related genes and the downregulation of fatty acid, glycolysis, differentiation, MYC, HNF4A, DNA repair genes. In conclusion, the clinical characteristics of SRCC are severe but there is a possibility of the presence of different phenotypes according to CMS analysis.
Insights
Signet ring cell carcinoma (SRCC) is a rare colorectal cancer subtype with more severe clinical features and worse survival. Molecular analysis suggests potential heterogeneity in consensus molecular subtypes (CMS), indicating diverse phenotypes.
Area of Science:
- Oncology
- Gastroenterology
- Pathology
Background:
- Signet ring cell carcinoma (SRCC) is a rare colorectal cancer subtype with poorly understood clinicopathological features and genetic background.
- Consensus molecular subtyping (CMS) has advanced colorectal cancer treatment, but its application to SRCC remains unclear.
Purpose of the Study:
- To investigate the clinicopathological features and molecular characteristics of signet ring cell carcinoma (SRCC) in colorectal cancer.
- To explore the potential Consensus Molecular Subtyping (CMS) of SRCC and its correlation with clinical outcomes.
Main Methods:
- Retrospective analysis of 1,350 colorectal cancer patients, identifying 14 with SRCC.
- Case-control study comparing SRCC patients with adenocarcinoma controls on clinicopathological variables.
- Microarray analysis and CMS classification of SRCC and adenocarcinoma samples.
Main Results:
- SRCC cases showed a predilection for the right colon, increased lymphatic invasion, and higher rates of peritoneal dissemination compared to controls.
- SRCC patients exhibited significantly worse cancer-specific survival and progression-free survival.
- Molecular analysis indicated SRCC cases could be assigned to CMS 4 and CMS 1 subtypes, with upregulation of EMT genes and downregulation of differentiation and DNA repair genes.
Conclusions:
- SRCC presents with aggressive clinical characteristics and poorer prognosis.
- The molecular heterogeneity of SRCC, suggested by CMS classification, implies diverse underlying phenotypes.
- Further research into SRCC subtypes may inform targeted treatment strategies.
