High Rab27A expression indicates favorable prognosis in CRC

Diagnostic Pathology

Pingsheng Chen⁴  Lin Xiong¹  Huijun Zhu⁷  Feng Zhan⁵  Li Xu³  Ning Hou³  Yijiang Ni⁶  Xiaojun Yang²  Chuanbing Shi⁴ 

[1] The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China;Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China;Department of Pathology, Jiangsu Cancer Hospital, Nanjing 210000, China;Department of Pathology and Pathophysiology, School of Medicine, Southeast University, Nanjing 210009, China;Department of Hepatobiliary and Laparoscopic Surgery, YiXing People’s Hospital, the Affiliated YiXing Hospital of Jiangsu University, Yixing 214200, China;Department of Traumatic Surgery, Changzhou No. 2 People’s Hospital Affiliated with Nanjing Medical University, Changzhou 213000, China;Department of Pathology and Laboratory Medicine, the Affiliated Hospital of Nantong University, Nantong 226000, China

关键词: Prognosis;    Metastasis;    IHC;    qPCR;    CRC;    Rab27A;   

Others  :  1219379
DOI  :  10.1186/s13000-015-0303-3

 received in 2014-10-28, accepted in 2015-05-29,  发布年份 2015

【 摘 要 】

Background

Rab27A is a peculiar member in Rab family and has been suggested to play essential roles in the development of human cancers. However, the association between Rab27A expression and clinicopathological characteristics of colorectal cancer (CRC) has not been elucidated yet.

Methods

One-step quantitative real-time polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 112 CRC cases were executed to evaluate the relationship between Rab27A expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for 112 CRC patients.

Results

The results specified that the expression levels of Rab27A mRNA and protein were significantly higher in CRC tissues than that in matched non-cancerous tissues, in both qPCR test (p = 0.029) and IHC analysis (p = 0.020). The IHC data indicated that the Rab27A protein expression in CRC was statistically correlated with lymph node metastasis (p = 0.022) and TNM stage (p = 0.026). Cox multi-factor analysis and Kaplan-Meier method suggested Rab27A protein expression (p = 0.012) and tumor differentiation (p = 0.004) were significantly associated with the overall survival of CRC patients.

Conclusion

The data indicated the differentiate expression of Rab27A in CRC tissues and matched non-cancerous tissues. Rab27A may be used as a valuable prognostic biomarker for CRC patients.

【 授权许可】

   
2015 Shi et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】

• [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a cancer journal for clinicians. 2011; 61(2):69-90.
• [2]Huang CW, Tsai HL, Chen YT, Huang CM, Ma CJ, Lu CY et al.. The prognostic values of EGFR expression and KRAS mutation in patients with synchronous or metachronous metastatic colorectal cancer. BMC cancer. 2013; 13:599. BioMed Central Full Text
• [3]Fang YJ, Wu XJ, Zhao Q, Li LR, Lu ZH, Ding PR et al.. Hospital-based colorectal cancer survival trend of different tumor locations from 1960s to 2000s. PloS one. 2013; 8(9): Article ID e73528
• [4]Kleespies A, Fuessl KE, Seeliger H, Eichhorn ME, Muller MH, Rentsch M et al.. Determinants of morbidity and survival after elective non-curative resection of stage IV colon and rectal cancer. Int J Colorectal Dis. 2009; 24(9):1097-1109.
• [5]Platell C, Ng S, O'Bichere A, Tebbutt N. Changing management and survival in patients with stage IV colorectal cancer. Diseases of the colon and rectum. 2011; 54(2):214-219.
• [6]Karoui M, Roudot-Thoraval F, Mesli F, Mitry E, Aparicio T, Des Guetz G et al.. Primary colectomy in patients with stage IV colon cancer and unresectable distant metastases improves overall survival: results of a multicentric study. Diseases of the colon and rectum. 2011; 54(8):930-938.
• [7]Atkin WS, Edwards R, Kralj-Hans I, Wooldrage K, Hart AR, Northover JM et al.. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010; 375(9726):1624-1633.
• [8]Chen C, Wang L, Liao Q, Huang Y, Ye H, Chen F et al.. Hypermethylation of EDNRB promoter contributes to the risk of colorectal cancer. Diagnostic pathology. 2013; 8:199. BioMed Central Full Text
• [9]Li Y, Wei J, Xu C, Zhao Z, You T. Prognostic significance of cyclin d1 expression in colorectal cancer: a meta-analysis of observational studies. PloS one. 2014; 9(4): Article ID e94508
• [10]Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nature reviews Molecular cell biology. 2009; 10(8):513-525.
• [11]Hutagalung AH, Novick PJ. Role of Rab GTPases in membrane traffic and cell physiology. Physiological reviews. 2011; 91(1):119-149.
• [12]Fukuda M. Rab27 effectors, pleiotropic regulators in secretory pathways. Traffic. 2013; 14(9):949-963.
• [13]Van Gele M, Dynoodt P, Lambert J. Griscelli syndrome: a model system to study vesicular trafficking. Pigment cell & melanoma research. 2009; 22(3):268-282.
• [14]Wang JS, Wang FB, Zhang QG, Shen ZZ, Shao ZM. Enhanced expression of Rab27A gene by breast cancer cells promoting invasiveness and the metastasis potential by secretion of insulin-like growth factor-II. Molecular cancer research : MCR. 2008; 6(3):372-382.
• [15]Montel V, Huang TY, Mose E, Pestonjamasp K, Tarin D. Expression profiling of primary tumors and matched lymphatic and lung metastases in a xenogeneic breast cancer model. The American journal of pathology. 2005; 166(5):1565-1579.
• [16]Wu X, Hu A, Zhang M, Chen Z. Effects of Rab27a on proliferation, invasion, and anti-apoptosis in human glioma cell. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2013; 34(4):2195-2203.
• [17]Bobrie A, Krumeich S, Reyal F, Recchi C, Moita LF, Seabra MC et al.. Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer research. 2012; 72(19):4920-4930.
• [18]Wang H, Zhao Y, Zhang C, Li M, Jiang C, Li Y. Rab27a was identified as a prognostic biomaker by mRNA profiling, correlated with malignant progression and subtype preference in gliomas. PloS one. 2014; 9(2): Article ID e89782
• [19]Dong WW, Mou Q, Chen J, Cui JT, Li WM, Xiao WH. Differential expression of Rab27A/B correlates with clinical outcome in hepatocellular carcinoma. World journal of gastroenterology : WJG. 2012; 18(15):1806-1813.
• [20]Luo B, Yun X, Fan R, Lin YD, He SJ, Zhang QM et al.. Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters. International journal of clinical and experimental pathology. 2013; 6(12):2835-2845.
• [21]Fu M, Fan W, Pu X, Ni H, Zhang W, Chang F et al.. Elevated expression of SHIP2 correlates with poor prognosis in non-small cell lung cancer. International journal of clinical and experimental pathology. 2013; 6(10):2185-2191.
• [22]Fu M, Gu X, Ni H, Zhang W, Chang F, Gong L et al.. High expression of inositol polyphosphate phosphatase-like 1 associates with unfavorable survival in hepatocellular carcinoma. International journal of clinical and experimental pathology. 2013; 6(11):2515-2522.
• [23]Mao Y, Zhang DW, Zhu H, Lin H, Xiong L, Cao Q et al.. LMP1 and LMP2A are potential prognostic markers of extranodal NK/T-cell lymphoma, nasal type (ENKTL). Diagnostic pathology. 2012; 7:178. BioMed Central Full Text
• [24]Zhang H, Qiu J, Ye C, Yang D, Gao L, Su Y et al.. ROR1 expression correlated with poor clinical outcome in human ovarian cancer. Scientific reports. 2014; 4:5811.
• [25]Lin H, Zhang H, Wang J, Lu M, Zheng F, Wang C et al.. A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo. International journal of cancer Journal international du cancer. 2014; 134(5):1239-1249.
• [26]Zhu H, Lu J, Wang X, Zhang H, Tang X, Zhu J et al.. Upregulated ZO-1 correlates with favorable survival of gastrointestinal stromal tumor. Medical oncology. 2013; 30(3):631.
• [27]Gu X, Fu M, Ge Z, Zhan F, Ding Y, Ni H et al.. High expression of MAGE-A9 correlates with unfavorable survival in hepatocellular carcinoma. Scientific reports. 2014; 4:6625.
• [28]Cheng KW, Lahad JP, Kuo WL, Lapuk A, Yamada K, Auersperg N et al.. The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nature medicine. 2004; 10(11):1251-1256.
• [29]Fan Y, Xin XY, Chen BL, Ma X. Knockdown of RAB25 expression by RNAi inhibits growth of human epithelial ovarian cancer cells in vitro and in vivo. Pathology. 2006; 38(6):561-567.
• [30]Hou Q, Wu YH, Grabsch H, Zhu Y, Leong SH, Ganesan K et al.. Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer research. 2008; 68(12):4623-4630.
• [31]Hendrix A, Maynard D, Pauwels P, Braems G, Denys H, Van den Broecke R et al.. Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis. Journal of the National Cancer Institute. 2010; 102(12):866-880.
• [32]Zeelenberg IS, Ostrowski M, Krumeich S, Bobrie A, Jancic C, Boissonnas A et al.. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer research. 2008; 68(4):1228-1235.
• [33]Taylor DD, Gercel-Taylor C. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Seminars in immunopathology. 2011; 33(5):441-454.
• [34]Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G et al.. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature medicine. 2012; 18(6):883-891.