Expression of Glioma-associated Oncogene Homolog 1 is Associated with Invasion and Postoperative Liver Metastasis in Colon Cancer

Abstract

Objective: To investigate the expression of glioma-associated oncogene homolog 1(Gli-1) in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis.Methods: Expression of Gli-1 was detected by immunohistochemistry in paraffin-embedded specimens of 96 cases of colon cancer. Relationship between Gli-1 expression and clinicopathological parameters, postoperative liver metastasis were analyzed.Results: Gli-1 protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.037). Gli-1 expression in colon tissues was increased in patients with lymph node metastases (P = 0.022) and higher T stages (P = 0.030). Postoperative live metastasis-free survival period was significantly longer in low Gli-1 expression group than that of high Gli-1 expression group (48.22±10.03 months vs 20.46±6.32 months, P=0.001). Multivariate analysis showed that Gli-1 expression level is an independent prognostic factor for postoperative live metastasis-free survival.Conclusion: Colon cancer is associated with an upregulation of Gli-1 protein expression in colon tissues. In patients with colon cancer, Gli-1 expression level is closely related to lymph node metastases, T stages and postoperative live metastasis-free survival periods, indicative of a possible role of Gli-1 expression in colon cancer progression.

The Prognostic Significance of the Hedgehog Signaling Pathway in Colorectal Cancer

“…[61][62][63][64][65] There is conflicting information about the prognostic role of the Hh pathway in colorectal malignancies. High cytoplasmic protein expression of Shh, Ptch1, and Smo predicted for adverse disease-free and overall survival, 38 high Smo and nuclear Gli1 expression predicted for liver metastasis-free survival, 39,40 and Smo expression predicted for better CRC-specific survival but only in the CIMP high expression subgroup. 53 Finally, Gli1 polymorphisms could predict for time to recurrence.…”

“…43 Yoshikawa et al also failed to confirm the prognostic significance of Shh, Ptch1, and Smo in terms of survival. 32 Ding et al suggested that high Smo and Gli1 expression were predictive for poor postoperative liver metastasis-free survival, 39,40 however, in that study it is not clear if patients received adjuvant chemotherapy after resection. Moreover, another study by Li et al failed to confirm the prognostic significance of Smo.…”

“…Increased Gli1 and Sufu expression have been correlated with advanced T stage 24,38,40 and lymph node involvement. 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 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.…”