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Downregulated SPINK4 is associated with poor survival in colorectal cancer
Xiaojie Wang1, Qian Yu2, Waleed M Ghareeb1,3
1Department of Colorectal Surgery, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian, 350001, People's Republic of China.
Background:
SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown.
Methods:
We retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center.
Results:
SPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort.
Conclusions:
We concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.
Insights
Reduced SPINK4 expression in colorectal cancer (CRC) correlates with poor patient survival. This study identifies SPINK4 as a novel prognostic indicator for CRC, highlighting its clinical significance.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- SPINK4 is a gastrointestinal peptide primarily found in goblet cells.
- The clinical role of SPINK4 in colorectal cancer (CRC) remains largely uninvestigated.
Purpose of the Study:
- To investigate the expression levels of SPINK4 in CRC tissues compared to normal tissues.
- To evaluate the prognostic value of SPINK4 in predicting survival outcomes for CRC patients.
Main Methods:
- Analysis of SPINK4 mRNA expression in 1168 CRC patients using public datasets (GEO, TCGA).
- Validation of SPINK4 protein levels via Human Protein Atlas and immunohistochemistry in 81 CRC cases.
- Correlation analysis between SPINK4 expression and clinicopathological features, including TNM stage.
Main Results:
- SPINK4 expression was significantly downregulated in colorectal cancer tissues compared to normal tissues.
- Lower SPINK4 mRNA and protein levels were consistently associated with poorer survival across multiple datasets and the in-house cohort.
- Decreased SPINK4 expression correlated with advanced TNM stage and was identified as an independent predictor of poor prognosis in CRC.
Conclusions:
- Reduced SPINK4 expression is linked to unfavorable survival outcomes in colorectal cancer patients.
- SPINK4 serves as a novel and independent prognostic biomarker for colorectal cancer.
