High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy

Hu, Chunhui; Chen, Beibei; Zhou, Yibin; Shan, Yuxi

doi:10.1186/s12935-017-0411-0

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…Members of the RAB family regulate vesicle trafficking and are known to both promote and suppress tumor growth, depending on the family member and cancer type [34]. Although increased expression of RAB25 has been shown to contribute to prostate cancer malignancy and recurrence [35], similar studies or observations involving RAB17 are lacking.…”

Section: Cancer-specific Featuresmentioning

confidence: 99%

Machine learning-based investigation of the cancer protein secretory pathway

Saghaleyni

Muhammad

Bangalore³

et al. 2020

Preprint

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Deregulation of the protein secretory pathway (PSP) is linked to many hallmarks of cancer, such as promoting tissue invasion and modulating cell-cell signaling. The collection of secreted proteins processed by the PSP, known as the secretome, is often studied due to its potential as a reservoir of tumor biomarkers. However, there has been less focus on the protein components of the secretory machinery itself. We therefore investigated the expression changes in secretory pathway components across many different cancer types. Specifically, we implemented a dual approach involving differential expression analysis and machine learning to identify PSP genes whose expression was associated with key tumor characteristics: mutation of p53, cancer status, and tumor stage. Eight different machine learning algorithms were included in the analysis to enable comparison between methods and to focus on signals that were robust to algorithm type. The machine learning approach was validated by identifying PSP genes known to be regulated by p53, and even outperformed the differential expression analysis approach. Among the different analysis methods and cancer types, the kinesin family members KIF20A and KIF23 were consistently among the top genes associated with malignant transformation or tumor stage. However, unlike most cancer types which exhibited elevated KIF20A expression that remained relatively constant across tumor stages, renal carcinomas displayed a more gradual increase that continued with increasing disease severity. Collectively, our study demonstrates the complementary nature of a combined differential expression and machine learning approach for analyzing gene expression data, and highlights key PSP components relevant to features of tumor pathophysiology that may constitute potential therapeutic targets.Author SummaryThe secretory pathway is a series of intracellular compartments and enzymes that process and export proteins from the cell to the surrounding environment. Dysfunction of the secretory pathway is associated with many diseases, including cancer, and therefore constitutes a potential target for novel therapeutic strategies. The large number of interacting components that comprise the secretory pathway pose a challenge when attempting to identify where the dysfunction originates and/or how to restore healthy function. To improve our understanding of how the secretory pathway is changed within tumors, we used gene expression data from normal tissue and tumor samples from thousands of individuals which included many different types of cancers. The data was analyzed using various machine learning algorithms which we trained to predict sample characteristics, such as disease severity. This training quantified the relative degree to which each gene was associated with the tumor characteristic, allowing us to predict which secretory pathway components were important for processes such as tumor progression—both within specific cancer types and across many different cancer types. Our approach demonstrated excellent performance compared to traditional gene expression analysis methods and identified several secretory pathway components with strong evidence of involvement in tumor development.

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Section: Cancer-specific Featuresmentioning

confidence: 99%

Machine learning-based investigation of the cancer protein secretory pathway

Saghaleyni

Muhammad

Bangalore³

et al. 2020

Preprint

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“…Rab25 functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner. It was predominantly reported to have oncogenic function and elevated expression in cancer, including ovarian cancer [ 12 , 13 ], breast cancer [ 12 – 14 ], renal cancer [ 15 , 16 ], gastric cancer [ 17 ], liver cancer [ 18 ], non-small cell lung cancer [ 19 ], bladder cancer [ 20 ], glioblastoma multiforme [ 21 ] and prostate cancer [ 22 ]. Tumor suppressor function of Rab25 has also been found in several types of cancer, including colon cancer [ 23 ], head and neck cancer [ 24 ], esophageal squamous cell carcinoma [ 25 ] and oral and oropharyngeal squamous cell carcinoma [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…It has been demonstrated that Rab25 enhances cell proliferation and tumor development. Knockdown of Rab25 expression by siRNA / shRNA transfection inhibited in vitro cell growth of renal cell carcinoma cells (786-O and A-498) [ 16 ], prostate cancer cells (LNCaP) [ 22 ] and hepatocellular carcinoma cells (Bel7402 and SK-Hep-1) [ 45 ]. Suppression of both in vitro cell growth and in vivo xenograft development were observed after knockdown of Rab25 in glioblastoma multiforme cells (U87MG) [ 21 ] and breast cancer cells (MCF7) [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

“…Current reports indicated the involvement of Rab25 in promoting cell migration and invasion. Knockdown of Rab25 suppressed in vitro cell migration and cell invasion in renal cell carcinoma cells [ 16 ], advanced non-small cell lung cancer cells [ 19 ], prostate cancer cells [ 22 ] and glioblastoma multiforme cells [ 21 ]. Suppression of cell invasion after Rab25 knockdown was observed in gastric cancer cells [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…A large majority of clinicopathological findings indicate the oncogenic role of Rab25 in cancer. Elevated expression of Rab25 was significantly associated with shorter survival time of patients with bladder cancer [ 20 ], advanced non-small cell lung cancer [ 19 ], ovarian cancer [ 12 ], breast cancer [ 12 , 49 ], clear cell renal cell carcinoma [ 15 ] and prostate cancer [ 22 ]. It is indicated that Rab25 is a potential prognostic marker for patients with various types of cancer.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rab25 GTPase: Functional roles in cancer

Wang

et al. 2017

Oncotarget

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Rab25, a small GTPase belongs to the Rab protein family, has a pivotal role in cancer pathophysiology. Rab25 governs cell-surface receptors recycling and cellular signaling pathways activation, allowing it to control a diverse range of cellular functions, including cell proliferation, cell motility and cell death. Aberrant expression of Rab25 was linked to cancer development. Majority of research findings revealed that Rab25 is an oncogene. Elevated expression of Rab25 was correlated with poor prognosis and aggressiveness of renal, lung, breast, ovarian and other cancers. However, tumor suppressor function of Rab25 was reported in several cancers, such as colorectal cancer, indicating the tumor type-specific function of Rab25. In this review, we recapitulate the current knowledge of Rab25 in cancer development and therapy.

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Rab25 and RCP in cancer progression

Lee

2019

Arch. Pharm. Res.

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High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy

Cited by 12 publications

References 27 publications

Machine learning-based investigation of the cancer protein secretory pathway

Machine learning-based investigation of the cancer protein secretory pathway

Rab25 GTPase: Functional roles in cancer

Rab25 and RCP in cancer progression

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