LIM and SH3 domain protein 1 (LASP-1) overexpression was associated with aggressive phenotype and poor prognosis in clear cell renal cell cancer.

LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein that is known to be involved in numerous biological and pathological processes. LASP-1 overexpression has been described in several types of cancers, but its expression and role in clear cell renal cell cancer (ccRCC) remains unknown.Using immunohistochemistry, we analyzed LASP-1 protein expression in 216 clinicopathologically characterized ccRCC cases. We also examined LASP-1 expression in 20 paired ccRCC tissues and in 2 cell lines by real-time PCR and Western blot. Using RNA interference, we investigated the effects of LASP-1 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine the associations between LASP-1 levels, tumor features and patient outcomes.LASP-1 overexpression was observed in ccRCC tissues (P<0.0001) compared to adjuvant nontumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (P = 0.044 and 0.006, respectively) in patients with ccRCC. RNA interference-mediated silencing of the LASP-1 gene in 786-0 ccRCC cells significantly inhibited cell migration.The results of the present study indicate that LASP-1 may serve as a prognostic biomarker for ccRCC patients and may be a promising target for the treatment of ccRCC

LIM and SH3 protein 1 (LASP-1) expression in clear cell renal cell cancer (ccRCC) tissues and cell lines.

<p>LASP-1 protein expression in paraffin-embedded ccRCC tissues (A) and adjacent nontumorous tissues (B) using immunohistochemistry (magnification, 100×), in which positive LASP-1 immunostaining showed brown color. Wilcoxon analysis demonstrated that tumor tissues showed significantly higher LASP-1 expression than nontumorous tissues (C, n = 216). Western blot (D) and real-time PCR (E, n = 20) analyses confirmed the findings in immunohistochemistry analysis. Western blot analysis also showed differential LASP-1 expression in human embrynal kidney cells (HEK-293) and ccRCC cell lines (F). T refers to tumor tissues, whereas P refers to peritumor (nontumorous) tissues in panel D.</p

Association between LASP-1 expression and clinical characteristics in ccRCC patients.

<p>Abbreviations: ccRCC, clear cell renal cell cancer; LASP-1, LIM and SH3 protein 1.</p

LASP-1 silencing inhibited RCC cell migration in vitro.

<p>Western blotting was used to verify knock-down of LASP-1 expression in 786–0 cells by siRNA transfection (A). An unpaired t-test was used to assess differences in the number of invaded cells per field between the 786–0 and si786–0 cell lines (B). Transwell results for the 786–0 and si786–0 cell lines are shown (C).</p

LIM and SH3 protein 1 (LASP-1) overexpression in clear cell renal cell cancer (ccRCC) is associated with poor overall survival (A) and recurrence free survival (B).

<p>LIM and SH3 protein 1 (LASP-1) overexpression in clear cell renal cell cancer (ccRCC) is associated with poor overall survival (A) and recurrence free survival (B).</p

Univariate Cox regression analysis of the prognostic factors for ccRCC.

<p>Abbreviations: CI, confidence interval; ccRCC, clear cell renal cell cancer; HR, hazard ratio; LASP-1, LIM and SH3 protein 1.</p