55704

CCDC88A

coiled-coil domain containing 88A;CCDC88A;coiled-coil domain containing 88A

AKT-phosphorylation enhancer|Hook-related protein 1|g alpha-interacting vesicle-associated protein|girders of actin filament|girders of actin filaments|girdin

2p16.1

protein-coding

To investigate the expression status and the clinical implications of Girdin protein in breast cancer. The expression status of Girdin protein and clinicopathological parameters in 820 breast cancer specimens was analyzed using immunohistochemistry staining and the relationship between Girdin protein and clinicopathological parameters. The prognosis of breast cancer was subsequently determined. Girdin protein was expressed positively in 295 (35.98%) of the 820 cases examined. The expression of Girdin protein was related to histological type and CerbB2 (P = 0.001, 0.006, and 0.001, respectively). After analyzing survival rates, the cases with highly expressed Girdin protein were shown to attain a significantly more distant metastasis rate and poorer postoperative, disease-specific survival than those with none or low expressed Girdin protein (P = 0.001). In the Cox regression test, Girdin protein was detected as an independent prognostic factor (P = 0.031). Girdin protein may be a potential new distant metastasis biomarker of breast cancer.

AIMS AND BACKGROUND: Increasing evidence claims that autophagy is essential for breast cancer progression. Girdin was found highly expressed in breast cancers. It has been reported that Girdin attenuates autophagy in HeLa cells. We explored the relationship between Girdin expression and autophagic patterns in breast cancer. METHODS AND STUDY DESIGN: In the study, Girdin expression and autophagic activity were investigated in a series of 99 invasive ductal breast carcinomas after immunohistochemical staining for the autophagy-associated proteins LC3-II and Girdin. RESULTS: The level of Girdin expression negatively correlated with LC3-II level, which represents autophagic activity (r = -0.289), and positively correlated with lymph node metastasis (r = 0.472). Girdin level was found no different in the "diffuse cytoplasmic" and "stone-like" patterns of LC3-II. CONCLUSIONS: Up-regulated autophagy was negatively associated with Girdin level. There was a significant correlation between Girdin expression and lymph nodes metastasis in invasive ductal breast carcinoma.

metastasis accounts for the majority of cancer-related deaths. Accurate prediction of metastatic potential of tumors has been elusive, and the search for clinically useful markers continues. We previously reported that GIV/Girdin triggers tumor cell migration by virtue of a C-terminal guanine-nucleotide exchange factor motif that activates Galphai. Here we identify GIV as a metastasis-related protein whose full-length transcript (GIV-fl) is expressed exclusively in highly invasive colon, breast, and pancreatic carcinoma cells and not in their poorly invasive counterparts. A prospective, exploratory biomarker study conducted on a cohort of 56 patients with stage II colorectal cancer revealed a significant correlation between GIV-fl expression in tumor epithelium and shortened metastasis-free survival. Survival rate for patients with GIV-fl-positive tumors is significantly reduced compared with the patients with GIV-fl-negative tumors [P<0.0001; hazard ratio=0.076; CI=0.052-0.30 (95%)]. At the 5-yr mark, survival is 100% in the GIV-fl-negative group and 62 +/- 9% (mean+/-SE; P=6x10(-5)) in the GIV-fl-positive group. Furthermore, GIV-fl expression predicts a risk of mortality independent of the microsatellite stability status, a well-established prognosticator of colorectal cancers. We conclude that GIV-fl is a novel metastasis-related protein and an independent adverse prognosticator that may serve as a useful adjunct to traditional staging strategies in colorectal carcinoma.

The objective of this study is to investigate the livers metastasis-related genes and the relationship between Girdin protein expression and clinical and pathological characteristics and prognosis in colorectal cancer. The differential expression of genes between tumor cells from cases with liver metastasis and those from cases without liver metastasis were detected using an RT(2) Profiler PCR Array. The expression of the stem cell gene Girdin was analyzed using immunohistochemistry staining. Subsequently, the relationship between Girdin and clinicopathological parameters of colorectal cancer was determined. The Girdin protein was verified as a gene related to liver metastasis and was expressed positively in 161 (37.01 %) of the 435 cases examined. The expression of Girdin protein was related to histological grade and distant metastasis (P = 0.007 and 0.007, respectively). After analyzing survival rates, cases with highly expressed Girdin protein were shown to attain a significantly higher rate of liver metastasis and poorer postoperative, disease-specific survival than those with no or low expressed Girdin protein (P = 0.001). In the Cox regression test, the depth of tumor invasion, histological grade, dukes stage, distant metastasis, and the Girdin protein were detected as an independent prognostic factor (0.020, 0.032, 0.001, 0.001, and 0.010, respectively). The Girdin protein may be a potential new early liver metastasis biomarker of colorectal cancer.