Depolarized MUC1 Expression Is Closely Associated With Hypoxic Markers and Poor Outcome in Resected Non–Small Cell Lung Cancer

Abstract

MUC1 is transmembrane mucin aberrantly overexpressed in various cancers. However, little is known about how MUC1 expression is associated with hypoxia, glucose metabolism, and epidermal growth factor receptor (EGFR) pathway, which are related to cancer progression. The aim of this study is to evaluate the relationship between MUC1 expression and these molecular markers in lung cancer. Of all 126 patients, high-grade polarized expression (HP), low-grade polarized expression (LP), and depolarized expression (DP) group were 50 (39.7%), 35 (27.8%), and 41 (32.5%), respectively. Depolarized MUC1 expression was significantly associated with poor outcome and was closely correlated with glucose metabolism (Glut1), hypoxia (HIF-1α), angiogenesis (vascular endothelial growth factor and microvessel density), amino acid metabolism (LAT1), and EGFR expression. High-grade polarized MUC1 expression was associated with favorable prognosis and adenocarcinoma. Depolarized MUC1 expression was significantly associated with poor outcome. Glucose metabolism, hypoxia, angiogenesis, amino acid metabolism, and EGFR pathway may play an important role in the development of depolarized MUC1 expression.

MUC1 and metastatic cancer

“…9 MUC1 expression is seen in all subtypes of breast cancer, including luminal, HER2 + studies in metastatic breast, colorectal, gall bladder, non-small cell lung and gastric cancer, using KL-6, discovered that MUC1 expression at the circumference of the plasma membrane and/or in the cytoplasm frequently correlated with deep invasion, lymph node or liver metastasis and decreased five-year survival. [40][41][42][43] These studies demonstrate that MUC1 detection in patient circulation and localization of expression in the tumor are important prognostic factors for metastasis and disease progression.…”

Expression of Amino Acid Transporters (LAT1 and ASCT2) in Patients with Stage III/IV Laryngeal Squamous Cell Carcinoma

“…The tumors in which the stained tumor cells were scored as 3, 4, or 5 were defined as positive; tumors scoring 4 or 5 were defined as having high expression. The immunohistochemical staining for CD34, Ki-67, and p53 was performed according to the procedures described in the previous reports [18][19][20]. The following antibodies were used: mouse monoclonal antibodies against CD34 (Nichirei, Tokyo, Japan; 1:800 dilution), Ki-67 (Dako, Glostrup, Denmark; 1:40 dilution), and p53 (D07; Dako; 1:50 dilution).…”

“…The anti-CD98 antibody used is an affinity-purified rabbit polyclonal antibody (Santa Cruz Biotechnology, Inc.; 1:100 dilution) raised against a peptide mapping to the carboxy terminus of human CD98. The detailed protocol for immunostaining has been published elsewhere [18][19][20]. The LAT1 and CD98 expression scores were defined by the extent of staining as follows: 1, ≤ 10 % of tumor area stained; 2, 11-25 % stained; 3, 26-50 % stained; 4, 51-75 % stained; and 5, ≥76 %.…”

“…ASCT2 is a major glutamine transporter and is associated with tumor growth and proliferation in cancer cells [4,11]. By several studies, both LAT1 and ASCT2 are shown to play crucial roles in the development and progression of various human neoplasms and are significant biomarkers for predicting worse outcome [7,[12][13][14][15][16][17][18][19][20][21][22][23]. But, the clinicopathological significance of amino acid transporters such as LAT1 and ASCT2 expression remains unknown in patients with LSCC.…”

Non-essential amino acids attenuate apoptosis of gastric cancer cells induced by glucose starvation

“…Thus, we examined the relative expression levels of amino acid transporter genes L-type amino acid transporter 1 (LAT1), LAT2 and h4F2hc. LAT1, as a transporter gene, is reported to be highly expressed in various human cancers (26)(27)(28)(29)(30)(31)(32), and its expression is strongly correlated with that of another amino acid transporter gene, h4F2hc (26). We performed qRT-PCR to determine transporter gene expression after 48 h of low-glucose culture and found that the decrease in glucose concentration led to the significant upregulation of amino acid transporters (LAT1 and h4Fhc).…”