Context-dependent MAN1A1 protein expression in metastatic breast cancer progression predicts patient survival

Alterations in N-glycosylation are frequently observed in breast cancer metastasis but are not well understood. Recently, decreases in expression of the Golgi α-mannosidase I MAN1A1 have been linked to worse patient prognosis in breast cancer.

To examine MAN1A1 expression in breast cancer progression, we developed and conducted MAN1A1 immunostaining of breast cancer tissue microarrays (TMAs), which were analyzed using pathology-guided object classifiers, which identified normal breast epithelial cells, primary tumor cells, and metastatic tumor cells.

MAN1A1 protein expression was significantly increased in primary tumor and local lymph node metastasis for a cohort of patients without distant metastases (N = 48). Changes in MAN1A1 protein expression along the metastatic path were context-dependent, as well as associated with survival for a rare, limited cohort of terminal metastatic breast cancer patients (N = 16). For these patients, an increase in MAN1A1 expression from normal breast to primary tumor was concomitant with decreased survival time (p = 0.032, hazard ratio = 2.68), as was a decrease in MAN1A1 expression from primary tumor to metastasis (p = 0.0018, hazard ratio = 3.45).

In our pilot study, MAN1A1 protein expression is a significant actor in progression along the metastatic path, supporting further study into MAN1A1 as driver of breast cancer patient survival.