High intratumoral metastasis-associated in colon cancer-1 expression predicts poor outcomes of cryoablation therapy for advanced hepatocellular carcinoma

Abstract

BackgroundCryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC. Metastasis-associated in colon cancer-1 (MACC1) overexpression has been associated with poor prognosis of HCC, but its predictive value to post-cryoablation outcomes remains unknown in patients with BCLC stage C HCC.MethodsThis study assessed the safety and outcomes of cryoablation measured by time to progression (TTP) and overall survival (OS), and predictive value of MACC1 mRNA and protein overexpression in tumorous tissue to post-cryoablation outcomes in 120 advanced HCC patients with child-pugh class A or B by quantitative polymerase chain reaction and immunohistochemical staining. The potenial correlation of MACC1 and c-Met expression to tumor cell proliferation and apoptosis was also analyzed.ResultsThe cryoablation in patients with advanced unresectable HCC resulted in a median TTP and OS of 5.5 (4.2- 6.7) months and 10.5 (9.0-12.0) months, respectively and no significant complications, comparable to the historical report for RFA therapy. The MACC1 mRNA and nuclear protein expression was significantly increased in tumorous tissues in these patients than that in normal liver tissue controls. Higher expression of MACC1 mRNA and nuclear protein in tumorous tissues in these patients was associated with shorter post cryoablation median TTP and OS than that with lower MACC1 expression.ConclusionsCryoablation is a safe and effective therapeutic option for patients with advanced HCC and Child-pugh class A or B cirrhosis; and a higher intratumoral expression of MACC1 or nuclear translocation predicts poor outcomes of cryotherapy in these patients.

Advances in Clinical Application of Cryoablation Therapy for Hepatocellular Carcinoma and Metastatic Liver Tumor

“…10 A total of 120 patients with Child-Pugh class A or B cirrhosis and advanced BCLC stage C unresectable HCC underwent cryoablation. 46 The median TTP and OS were 5.5 (4.2 to 6.7) and 10.5 (9.0 to 12.0) months, respectively, which were comparable with the previously reported TTP and OS rates when using RFA 49 or sorafenib therapy. 50 Clearly, above recent studies, especially the larger study by Yang et al 10,46 strongly support the clinical benefits and indications of cryotherapy for treating HCC, including advanced stage of HCC, in patients with ChildPugh class A or B cirrhosis.…”

“…46 The median TTP and OS were 5.5 (4.2 to 6.7) and 10.5 (9.0 to 12.0) months, respectively, which were comparable with the previously reported TTP and OS rates when using RFA 49 or sorafenib therapy. 50 Clearly, above recent studies, especially the larger study by Yang et al 10,46 strongly support the clinical benefits and indications of cryotherapy for treating HCC, including advanced stage of HCC, in patients with ChildPugh class A or B cirrhosis. However, further studies, especially multicenter studies, are needed to identify the clinical, biochemical, and histologic parameters that help in better selection of suitable HCC candidate patients for best outcomes of cryoablation.…”

“…Thus, MACC1 expression may serve as a potential biomarker in predicting outcomes when using cryoablation for HCC. [44][45][46] Wang and colleagues evaluated the risk factors that predict posttreatment metastasis and recurrence in 156 patients with hepatitis B virus (HBV)-related HCC < 5 cm in diameter who underwent cryoablation. The multivariate analysis showed that expression of vascular endothelial growth factor in HCC tissues and HBV basal core promoter mutations were independent prognostic factors for recurrence-free survival.…”

The expression of metastasis-associated in colon cancer-1 and KAI1 in gastric adenocarcinoma and their clinical significance

“…MACC1 was also an independent prognostic factor for colon cancer [3, 5]. Now, more and more studies have demonstrated that MACC1 could also be a metastatic and prognostic factor for various human cancers, including pancreatic [10], liver [11], lung [12], ovary [13], breast [14], gastric [8], malignant glioma [15], and cervical carcinoma [16]. …”

MACC1 Induces Tumor Progression in Transgenic Mice and Colorectal Cancer Patients via Increased Pluripotency Markers Nanog and Oct4

“…MACC1 was found significantly upregulated in primary colon cancer and organ metastases compared with normal tissues, indicating that the induction of MACC1 might occur at the crucial step of transition from the benign to the malignant phenotype in the adenomacarcinoma sequence of colorectal cancer (7,9). MACC1 has been described as a prognostic biomarker for tumor progression, metastasis, and survival in different solid tumors (10), including hepatocellular carcinoma (11)(12)(13)(14)(15)(16)(17)(18)(19), gastric (20,21), esophageal (22,23), cervical (24,25), and lung cancer (26)(27)(28). Met was identified as the first transcriptional target of MACC1, suggesting that MACC1 might signal through the HGF-Met pathway to promote tumor growth and metastasis.…”