Gene expression profiling-derived immunohistochemistry signature with high prognostic value in colorectal carcinoma

Chang, Wenjun; Xian, Gao; Han, Yaling; Du, Yan; Liu, Qizhi; Wang, Lei; Tan, Xiaojie; Zhang, Qi; Liu, Yan; Zhu, Yan; Ye, Yu; Fan, Xinjuan; Zhang, Hongwei; Zhou, Weiping; Wang, Jianping; Fu, Chuangang; Cao, Guangwen

doi:10.1136/gutjnl-2013-305475

Cited by 65 publications

(68 citation statements)

References 54 publications

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“…Baseline information on the specimen donors, including age, sex, disease location, grade, tumor size, depth of invasion, number of examined lymph nodes, and TNM stage (determined according to the American Joint Committee on Cancer Staging Manual, seventh edition), was also documented. Follow‐up information on patients with Stages I–III CRC was collected after a standard procedure as previously described . In our study, the outcome of interest was disease‐specific survival (DSS), which was defined in months from the date of surgery to the date of death due to CRC.…”

Section: Methodsmentioning

confidence: 99%

Clinical significance and biological function of WD repeat domain 54 as an oncogene in colorectal cancer

Yao

Shen

et al. 2018

Intl Journal of Cancer

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In recent years, protein-protein interactions have become an attractive candidate for identifying biomarkers and drug targets for various diseases. However, WD40 repeat (WDR) domain proteins, some of the most abundant mediators of protein interactions, are largely unexplored. In this study, 57 of 361 known WDR proteins were identified as hub nodes, and a hub (WDR54) with elevated mRNA in colorectal cancer (CRC) was selected for further study. Immunohistochemistry of specimens from 945 patients confirmed the elevated expression of WDR54 in CRC, and we found that patients with WDR54-high tumors typically had a shorter disease-specific survival (DSS) than those with WDR54-low tumors, especially for the subgroup without well-differentiated tumors. Multivariate analysis showed that WDR54-high tumors were an independent risk factor for DSS, with a hazard ratio of 2.981 (95% confidence interval, 1.425-6.234; p = 0.004). Knockdown of WDR54 significantly inhibited the growth and aggressiveness of CRC cells and reduced tumor growth in a xenograft model. Each WDR54 isoform (a, b, and c) was found to reverse the inhibitory effect of WDR54 knockdown; however, only isoform c, which exhibited the highest expression, was increased in CRC cells. Sensitization of WDR54 knockdown to an SHP2 inhibitor was consistently found in CRC cells, and the underlying mechanism involved their common function in regulating AKT and ERK signaling. In conclusion, the present study is the first to investigate the significance of WDR54 in cancer and to conclude that WDR54 serves as an oncogene in CRC and may be a potential prognostic marker and therapeutic target. This article is protected by copyright. All rights reserved.

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Section: Methodsmentioning

confidence: 99%

Clinical significance and biological function of WD repeat domain 54 as an oncogene in colorectal cancer

Yao

Shen

et al. 2018

Intl Journal of Cancer

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“…Many studies have exploited microarray technology to investigate gene expression profiles (GEPs) in CRC in recent years, but only a small subset demonstrates clear prognostic significance [5-10]. Molecular markers such as mutations in Kirsten ras gene (KRAS) and BRAF as well as chromosome instability (CIN) and microsatellite instability (MSI) have been systematically analysed for prognostic potential in CRC[11].…”

Section: Introductionmentioning

confidence: 99%

A long non-coding RNA signature to improve prognosis prediction of colorectal cancer

et al. 2014

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Increasing evidence suggests long non-coding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, however, few related lncRNA signatures have been established for prediction of cancer prognosis. We aimed to develop a lncRNA signature to improve prognosis prediction of colorectal cancer (CRC). Using a lncRNA-mining approach, we performed lncRNA expression profiling in large CRC cohorts from Gene Expression Ominus (GEO), including GSE39582 test series(N=436), internal validation series (N=117); and two independent validation series GSE14333 (N=197) and GSE17536(N=145). We established a set of six lncRNAs that were significantly correlated with the disease free survival (DFS) in the test series. Based on this six-lncRNA signature, the test series patients could be classified into high-risk and low-risk subgroups with significantly different DFS (HR=2.670; P<0.0001). The prognostic value of this six-lncRNA signature was confirmed in the internal validation series and another two independent CRC sets. Gene set enrichment analysis (GSEA) analysis suggested that risk score positively correlated with several cancer metastasis related pathways. Functional experiments demonstrated three dysregulated lncRNAs, AK123657, BX648207 and BX649059 were required for efficient invasion and proliferation suppression in CRC cell lines. Our results might provide an efficient classification tool for clinical prognosis evaluation of CRC.

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“…Recently, we successfully constructed a tissue microarrays bank based on accumulated several hundred cases of different stage colorectal cancer specimens [19], and evaluated 25 colorectal cancer gene signatures in independent microarray datasets with prognosis information and built a subnetwork using signatures with high concordance and repeatable prognostic values [20]. Here, we further elucidated that aberrant expression of MRP3 in pretreatment biopsy specimens was significantly higher in the nCRT-resistant group than in the nCRT-sensitive group and independently predicted poor longterm prognosis in a large number of locally advanced rectal cancer patients receiving nCRT, as indicated by TRG scoring system and 5-year survival rate.…”

Section: Discussionmentioning

confidence: 99%

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

Zhang

Wang

et al. 2014

Cancer Letters

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Gene expression profiling-derived immunohistochemistry signature with high prognostic value in colorectal carcinoma

Abstract: Our immunohistochemistry signature may be clinically practical for personalised prediction of CRC prognosis.

Cited by 65 publications

References 54 publications

Clinical significance and biological function of WD repeat domain 54 as an oncogene in colorectal cancer

Clinical significance and biological function of WD repeat domain 54 as an oncogene in colorectal cancer

A long non-coding RNA signature to improve prognosis prediction of colorectal cancer

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

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