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Prognostic Value of LISCH7 mRNA in Plasma and Tumor of Colon Cancer Patients

Authors' Affiliations: Departments of ¹ Medical Oncology and ² Biostatistics, Hospital Universitario Puerta de Hierro, Madrid, Spain and Departments of ³ Gastroenterology and ⁴ Pathology, Hospital Virgen de la Salud, Toledo, Spain

Requests for reprints: Félix Bonilla, Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/San Martín de Porres, 4, E-28035 Madrid, Spain. Phone: 34-91-3445148; Fax: 34-91-3445189; E-mail: fbonilla.hpth{at}salud.madrid.org.

Purpose: LISCH7 is a gene potentially regulated by p53 that is up-regulated in metastasis development. Our hypothesis was that the expression of LISCH7 in primary colorectal tumors determined certain characteristics of the tumors, as well as their behavior, and that its identification in plasma could serve as a prognostic marker.

Experimental Design: We tested this hypothesis in a series of 115 tumors and normal tissues and in 83 plasmas from patients with sporadic colorectal carcinomas, as well as in 20 healthy control plasmas in which the expression levels of the gene were measured by real-time PCR. The expression data were contrasted with clinicopathologic variables.

Results: Although LISCH7 expression was not detected in any control plasma samples, it was positive in 25 (30.1%) plasmas from patients (P = 0.002). LISCH7 mRNA in plasma was significantly associated with the pathologic stage (P = 0.019), with lymph node metastasis (P = 0.008) and with vascular invasion (P = 0.005). Expression was not detected in any normal tissues but was detected in 80 tumor tissues, with a clear association found with vascular invasion (P = 0.027). Moreover, we show that LISCH7 was specifically expressed by the epithelial tumor cells. The adjusted overall survival study showed independent prognostic values for LISCH7 expression levels in tumor tissues (hazard ratio, 3.45; 95% confidence interval, 1.19-9.98).

Conclusions: Our results suggest that LISCH7 is a good tumor marker whose expression levels could be considered as a poor prognosis factor in human colon cancer. Furthermore, plasma is suggested as a feasible source of nucleic acids for subsequent noninvasive prognostic studies.