Downregulated SPINK4 is associated with poor survival in colorectal cancer

Xiaojie Wang,Waleed M Ghareeb,Yiyi Zhang,Ying Huang,Yanwu Sun,Jiayi Lin,Xingrong Lu,Qian Yu,Shenghui Huang,Pan Chi,Jin Liu

doi:10.1186/s12885-019-6484-5

Xiaojie Wang, Waleed M Ghareeb + Show 9 more

Open Access

https://doi.org/10.1186/s12885-019-6484-5

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Abstract

BackgroundSPINK4 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.MethodsWe 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.ResultsSPINK4 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.ConclusionsWe concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.

Highlights

SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells
Decreased SPINK4 mRNA expression was associated with poor prognosis in colorectal cancer patients in 3 independent databases (GSE24551, GSE39582, the The Cancer Genome Atlas (TCGA) database) and our own cohort
The mRNA expression of SPINK4 is downregulated in colorectal cancer (CRC) tissues To examine the levels of SPINK4 mRNA in CRC samples, we first analyzed SPINK4 mRNA expression by comparing 17 CRC tissues and paired adjacent normal tissues from the GSE32323 dataset, and the results indicated that the relative SPINK4 expression level was significantly decreased in CRC tissues compared with that in adjacent normal tissues (8.5 ± 2.2 vs. 10.5 ± 2.6, P = 0.016, Fig. 2a)

Summary

Introduction

SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. Despite significant progress in surgery, radiotherapy, chemotherapy, and targeted therapy, colorectal cancer (CRC) remains one of the leading cancer types in terms of incidence and cancer-related death worldwide [1]. This characteristic is partly due to a lack of diagnostic markers for the detection of CRC and inefficient treatment of late-stage colorectal cancer [1]. The longterm outcome varies widely, even in patients within the same TNM stage [3] This pathological prognostic prediction method alone may not accurately predict prognosis without incorporating molecular data of the tumor [4]. An increasing number of studies in this era of genomic medicine have focused on molecularly based prognostic markers, which are complementary to the pathological TNM system [5, 6]

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