Expression of Smoothened Protein in Colon Cancer and its Prognostic Value for Postoperative Liver Metastasis

Abstract

Asian Pacific J Cancer Prev, 13, 4001-4005 IntroductionColon cancer is one of the most common cancers in the world and has a high propensity for liver metastasis (Ochiai et al., 2008;Jemal et al., 2010;Yassin et al., 2010;Soydinc et al., 2011). The major cause of death from colon cancer is liver metastasis, which is usually resistant to conventional therapies (Fidler, 1990). 35%-55% of patients with colon cancer will develop liver metastases during the course of illness. Survival following hepatic resection of colorectal metastasis now approaches 35%-50%. However, the recurrence rate in 5 years is as high as approximately 65% (Mayo and Pawlik, 2009). Early treatment targeting colon cancer liver metastatic foci might be important for improving patient survival. To date, the precise mechanisms leading to liver metastasis in colon cancer remains unknown, and biomarkers for liver metastasis are still lacking.The hedgehog (Hh) signaling pathway is known to play essential roles in multiple aspects of embryonic development. Hh protein binds to its receptor human patched 1 homologue (PTCH1), and relieves PTCH1's inhibition on smoothened (SMO), allowing SMO to signal downstream to glioma-associated oncogene homolog (Gli) transcriptional factors, which activates the target genes

Clinicopathological Characteristics and Prognosis of Patients According to Recurrence Time After Curative Resection for Colorectal Cancer

“…Hence, molecular markers are needed as potential predictors for prognosis and facilitate treatment in colorectal cancer patients (Ding et al, 2012;Fang et al, 2012;Hu et al, 2013;Li et al, 2013). To our knowledge, this is the first report to compare the relationship between k-ras mutation status with early recurrence.…”

Abnormal Hedgehog pathway in myelodysplastic syndrome and its impact on patients' outcome

“…Our findings corroborate other studies that have identified SMO overexpression as being significantly associated with poor prognosis of hepatoblastoma, 14 malignant pleural mesothelioma, 15 and also as an independent prognostic factor for post-operative liver metastasis-free survival in colon cancer. 16 Recently, SMO expression was reported to induce fatal AML in a mouse model of MDS, resulting in a reduced survival and widespread expansion of immature myeloid cells.…”

The Prognostic Significance of the Hedgehog Signaling Pathway in Colorectal Cancer

“…40 Similarly, Shh was correlated with the depth of invasion 39 and N stage. 38,39 High levels of Shh protein expression 37,38 but low mRNA levels 44 were correlated with advanced stage (III/IV). In a study performed by Monzo et al, a trend for an increased frequency of metastasis related with low Shh mRNA was observed 44 whereas Yoshikawa et al 32 reported that high Shh protein expression predicted for liver metastasis.…”

“…In most of the studies there is stronger protein expression in the malignant tissue compared with the noncancerous, 7,23,24,36,[38][39][40][41][42][43] with the only exception being the study published by Alinger et al 22 Ihh protein is lost in CRC and adenomas and it is expressed in HPs and normal tissue. 28 At the mRNA level similar results have been reported with higher expression of Hh members compared with the normal tissue.…”

“…37 However, in most of the studies there was no correlation of the pathway member expression with tumor differentiation. 14,24,33,[37][38][39][40][41][43][44][45]49,51 Unlike differentiation, Hh expression seems to correlate with tumor stage. Increased Gli1 and Sufu expression have been correlated with advanced T stage 24,38,40 and lymph node involvement.…”