Validation study of MARCKSL1 as a prognostic factor in lymph node-negative breast cancer patients

Abstract

Protein expression of Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) has been identified as a prognostic factor in lymph-node negative (LN-) breast cancer patients. We aim to validate MARCKSL1 protein expression as a prognostic marker for distant metastasis-free survival (DMFS) in a new cohort of LN- breast cancer patients. MARCKSL1 expression was evaluated in 151 operable T1,2N0M0 LN- breast cancer patients by immunohistochemistry. Median follow-up time was 152 months, range 11–189 months. Results were compared with classical prognosticators (age, tumor diameter, grade, estrogen receptor, and proliferation) using single (Kaplan-Meier) and multivariate (Cox model) survival analysis. Thirteen patients (9%) developed distant metastases. With both single and multiple analysis of all features, MARCKSL1 did not show a significant prognostic value for DMFS (p = 0.498). Of the assessed classical prognosticators, only tumor diameter showed prognostic value (hazard ratio 9.3, 95% confidence interval 2.8–31.0, p <0.001). MARCKSL1 expression could not be confirmed as a prognostic factor in this cohort. Possible reasons include changes in diagnostic and treatment guidelines between the discovery and validation cohorts. Further studies are needed to reveal the potential biological role of this protein in breast cancer.

MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia

“…A previous systematic and integrative ‘omics’ strategy identified that MARCKSL1 was upregulated in ESCC tissues and that MARCKSL1 augments ESCC cell mobility in vitro, 15 but it remains unclear whether MARCKSL1 expression is notably associated with the clinicopathological characteristics of patients with ESCC. Therefore, an immunohistochemical assay was performed, and as described in previous reports, 19 we observed that MARCKSL1 staining showed strong membrane, granular and diffuse staining, suggesting that MARCKSL1 has different regional expression patterns and potentially distinctive functions in different regional localizations. Moreover, MARCKSL1 protein levels were significantly increased in ESCC tumor tissues ( n = 811) compared to adjacent esophageal epithelia ( n = 442).…”

“…MARCKSL1 has a significant prognostic value in lymph node‐negative breast cancer. 19 To explore whether the protein level of MARCKSL1 is related to prognosis in lymph node‐negative ESCC patients, Kaplan–Meier survival analysis was also performed in ESCC patients with lymph node‐negative ESCC ( n = 378) and showed that higher MARCKSL1 expression was markedly correlated with a poor survival rate (Figure 5H ). However, no correlations were found between MARCKSL1 expression and other clinicopathological characteristics including age, sex, tumor length, tumor location and TNM stage (Table 1 ).…”

“…Furthermore, it was demonstrated that ESCC patients with high expression levels ( n = 220, IHC score >6) of MARCKSL1 had a worse survival rate than those with low expression levels ( n = 464, IHC score ≤6) ( p = 0.0222) by Kaplan–Meier survival analysis (Figure 5G). MARCKSL1 has a significant prognostic value in lymph node‐negative breast cancer 19 . To explore whether the protein level of MARCKSL1 is related to prognosis in lymph node‐negative ESCC patients, Kaplan–Meier survival analysis was also performed in ESCC patients with lymph node‐negative ESCC ( n = 378) and showed that higher MARCKSL1 expression was markedly correlated with a poor survival rate (Figure 5H).…”

Circulating extracellular vesicle-derived MARCKSL1 is a potential diagnostic non-invasive biomarker in metastatic colorectal cancer patients

“…As a protein associated with the occurrence and development of various tumors, MARCKSL1 has been mainly verified as a potential tumor marker or a new therapeutic target in lung cancer 21 – 24 , liver cancer 25 – 27 , colorectal cancer and other tumors. In addition, there are ongoing studies on prostate cancer 28 , breast cancer 29 , 30 , esophageal cancer 31 , basal cell carcinoma 32 , squamous cell carcinoma 33 and other tumors, and their potential as markers is gradually attracting the attention of researchers. MARCKSL1 has been selected as a potential marker for distinguishing metastatic and nonmetastatic sporadic colorectal cancer (sCRC) and is highly expressed in patients with metastatic sCRC.…”

Identification of a prognostic evaluator from glutamine metabolic heterogeneity studies within and between tissues in hepatocellular carcinoma

“…In this study, we used six machine learning algorithms to construct a model of prognosis-related DEGs between subtypes, identified 30 genes involved in each machine learning model, and captured six of them to develop a risk evaluator. Each gene in the risk evaluator, PLXNA1 (Ho, 1988), MARCKSL1 (Egeland et al, 2019), IQGAP3 (Leone et al, 2021), PFN2 (Cui et al, 2016), PON1 (Bobin-Dubigeon et al, 2012, and TAK (Li et al, 2022), has been reported to be associated with the prognosis or progression of cancer. Here, the risk evaluator developed using these six genes was associated with potential factors affecting the prognosis of HCC, such as clinicopathological features, somatic mutations, tumor microenvironment indicators, and signaling pathways.…”