Downregulated SPINK4 is associated with poor survival in colorectal cancer.
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.
['Wang|Xiaojie|X|', 'Yu|Qian|Q|', 'Ghareeb|Waleed M|WM|', 'Zhang|Yiyi|Y|', 'Lu|Xingrong|X|', 'Huang|Ying|Y|', 'Huang|Shenghui|S|', 'Sun|Yanwu|Y|', 'Lin|Jiayi|J|', 'Liu|Jin|J|', 'Chi|Pan|P|http://orcid.org/0000-0001-8276-1337']
D000368:Aged D014408:Biomarkers, Tumor D015331:Cohort Studies D003106:Colon D003110:Colonic Neoplasms D015179:Colorectal Neoplasms D015536:Down-Regulation D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D008875:Middle Aged D011379:Prognosis D000074162:Serine Peptidase Inhibitors, Kazal Type D016019:Survival Analysis
SPINK4 Survival Colorectal cancer