Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

Martinho, Olga; Simões, Kleber; Longatto‐Filho, Adhemar; Jacob, Carlos Eduardo; Zilberstein, Bruno; Bresciani, Cláudio José Caldas; Gama-Rodrigues, Joaquim; Cecconello, Ivan; Alves, Venâncio Avancini Ferreira; Reis, Rui Manuel

doi:10.3892/or.2012.2179

Cited by 20 publications

(17 citation statements)

References 48 publications

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“…On the other hand, our results showed a statistical correlation with the absence of RKIP molecule expression and poor prognosis of STSs (table 2). These data are in accordance with other papers from our group, evaluating the RKIP protein expression profile in different types of tumors such as gastrointestinal stromal tumors, bladder cancer, gastric cancer and gliomas [12,15,21,22,23,24,25,30]. Thus, in the present study we showed that RKIP immunohistochemistry loss is an independent prognostic factor in a well-characterized series of 87 STSs [16,17,18].…”

Section: Discussionsupporting

confidence: 80%

“…Representative 3-μm-thick tissue sections were used for immunohistochemical analysis according to the streptavidin-biotin-peroxidase complex system (UltraVision Large Volume Detection System Anti-Polyvalent HRP; LabVision Corporation), as previously described [21,22,23,24,25]. Briefly, deparaffinized and rehydrated slides were submitted to heat-induced antigen retrieval for 20 min at 98°C with 10 m M citrate buffer (pH = 6.0).…”

Section: Methodsmentioning

confidence: 99%

“…The score used was the sum of the percentage of positive cells (0, negative; 1, less than 25% positive cells; 2, 26-50% positive cells; 3, more than 50% positive cells) and the staining intensity (0, negative; 1, weak; 2, moderate; 3, strong). Scores between 0 and 2 were classified as negative, 3 and 4 as moderately positive, and 5 and 6 as strongly positive [21,22,23,24,25]. …”

Section: Methodsmentioning

confidence: 99%

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Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

et al. 2016

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Objective: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown. Methods: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters. Results: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker. Conclusion: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis.

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Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

et al. 2016

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“…The level of SPINT2 staining was semi-quantitated by intensity scoring: 0, negative; 1, weak; 2, moderate; 3, strong (Bergum et al 2010;Martinho et al 2012;Martinho et al 2013). Tumor tissues that presented scores between 0 and 1 were classified as negative for SPINT2 staining, those that were scored as 2 demonstrated moderate positive staining, and those scoring 3 as strongly positive.…”

Section: Spint2 Immunohistochemistrymentioning

confidence: 99%

SPINT2 Deregulation in Prostate Carcinoma

Pereira

Almeida

Pinto

et al. 2015

J Histochem Cytochem.

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SummarySPINT2 is a tumor suppressor gene that inhibits proteases implicated in cancer progression, like HGFA, hepsin and matriptase. Loss of SPINT2 expression in tumors has been associated with gene promoter hypermethylation; however, little is known about the mechanisms of SPINT2 deregulation in prostate cancer (PCa). We aimed to analyze SPINT2 expression levels and understand the possible regulation by SPINT2 promoter hypermethylation in PCa. In a cohort of 57 cases including non-neoplastic and PCa tissues, SPINT2 expression and promoter methylation was analyzed by immunohistochemistry and methylation-specific PCR, respectively. Methylation status of the SPINT2 promoter was also evaluated by bisulfite sequencing and 5-aza-2'-deoxycytidine treatment. Oncomine and TCGA databases were used to perform in silico PCa analysis of SPINT2 mRNA and methylation levels. A reduction in SPINT2 expression levels from nonneoplastic to PCa tissues was observed; however, none of the cases exhibited SPINT2 promoter methylation. Both bisulfite sequencing and 5-aza demonstrated that SPINT2 promoter is not methylated in PCa cells. Bioinformatics approaches did not show downregulation of SPINT2 at the mRNA level and, in corroboration with our results, SPINT2 promoter region is reported to be unmethylated. Our study suggests an involvement of SPINT2 in PCa tumorigenesis, probably in association with a post-translational regulation of SPINT2. (J Histochem Cytochem 64:32-41, 2016)

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“…Thus, the present results suggest that RKIP may function as a suppressor of metastasis in TSCC. Furthermore, the loss of RKIP expression is associated with a poor prognosis in prostate (23), gastric (24), pancreatic (25), and bladder cancers (26) and glioma (27). In the present study, well-established prognostic markers, such as lymph node metastasis and an advanced pTNM stage, were significantly associated with patient survival time.…”

Section: Discussionmentioning

confidence: 54%

Clinicopathological features and prognostic implications of Raf kinase inhibitor protein downregulation in tongue squamous cell carcinoma

Chen²,

Liu

et al. 2015

Oncology Letters

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Abstract. Raf kinase inhibitor protein (RKIP) is recognized as a suppressor of metastasis, and the downregulation of RKIP is associated with aggressive events and a poor outcome in a variety of solid tumors. However, the clinical relevance of RKIP expression in tongue squamous cell carcinoma (TSCC) remains unclear. In the present study, the expression of RKIP in 85 pairs of TSCC and corresponding adjacent non-cancerous tissues, 30 matched metastatic lesions from the cervical lymph nodes and 32 oral leukoplakia samples were assessed using immunohistochemical methods. The association between RKIP expression and clinicopathological features was then evaluated. Kaplan-Meier survival analysis and Cox proportional hazards model were used to estimate the effect of RKIP expression on the survival time of patients with TSCC. The results revealed that RKIP expression was dramatically downregulated in TSCC, and to an even greater extent in metastatic lesions. RKIP downregulation was significantly associated with the presence of lymphatic metastasis and the clinical stage of TSCC. Furthermore, patients with low RKIP expression demonstrated a significantly shorter overall survival time. Multivariate analysis indicated that RKIP expression may be an independent prognostic factor in TSCC. In conclusion, the present findings indicate that the lack of RKIP expression is of clinical significance and may serve as a prognostic biomarker in TSCC.

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Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

Cited by 20 publications

References 48 publications

Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

SPINT2 Deregulation in Prostate Carcinoma

Clinicopathological features and prognostic implications of Raf kinase inhibitor protein downregulation in tongue squamous cell carcinoma

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