Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer

Abstract

Background: The mixed lineage kinase domain-like protein has recently been identified as a key downstream component of tumor necrosis factor-induced necroptosis, which is an important pathway of cancer cell death. The goal of the current study is to explore the expression of mixed lineage kinase domain-like protein in colon cancer tissues and evaluate the prognostic value in patients with colon cancer.

Methods: We collected normal and cancer colon tissues from 135 patients diagnosed with colon cancer after radical operation during July 2007 to April 2009 at The Affiliated Hospital of Qingdao University. Immunohistochemistry analysis was scored using an established scoring system. Kaplan-Meier survival curves were generated for recurrence-free survival and overall survival for all patients and 2 subsets of patients. The relationship between mixed lineage kinase domain-like protein expression and prognosis parameter (recurrence-free survival, overall survival) was analyzed by univariate and multivariate Cox regression analyses.

Results: The median age of all patients was 67 years and 56.3% were male. Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (78.6 vs 81.2 months; P = .011) in all patients. In the subset of 79 patients who received adjuvant chemotherapy, low expression of mixed lineage kinase domain-like protein was associated with decreased recurrence-free survival (60.4 vs 72.8 months; P = .032) and decreased overall survival (66.3 vs 72.9 months; P = .005). Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (74.9 vs 79.8 months; P = .006) and recurrence-free survival (69.6 vs 78.8 months; P = .005) among patients with Tumor Node Metastasis (TNM) stage II colon cancer.

Conclusions: Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival in all patient-group with resected colon cancer. It is associated with decreased recurrence-free survival and overall survival in the subset of patients who receive adjuvant chemotherapy and patients who were TNM stage II. Mixed lineage kinase domain-like protein may provide important prognostic information in patients with colon cancer.

Keywords: MLKL; colon cancer; necroptosis; prognostic value.

Figure 1.

Representative images of mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining in colon cancer tissues (magnification ×400). A, High expression. B, Low expression. C, Negative expression.

Figure 2.

Kaplan-Meier log-rank survival analysis is shown for mixed lineage kinase domain-like protein (MLKL) expression in all patients (n = 135). A, The effect of MLKL expression on recurrence-free survival. B, The effect of MLKL expression on overall survival.

Figure 3.

Kaplan-Meier log-rank survival analysis is shown for mixed lineage kinase domain-like protein (MLKL) expression in patients receiving adjuvant chemotherapy (n = 79). A, The effect of MLKL expression on recurrence-free survival. B, The effect of MLKL expression on overall survival.

Figure 4.

Kaplan-Meier log-rank survival analysis is shown for mixed lineage kinase domain-like protein (MLKL) expression in patients receiving adjuvant chemotherapy (n = 79). A, The effect of MLKL expression on recurrence-free survival. B, The effect of MLKL expression on overall survival.