A novel Tn antigen epitope‑recognizing antibody for MUC1 predicts clinical outcome in patients with primary lung adenocarcinoma

Mucin 1 (MUC1) expression is upregulated in multiple types of cancer, including lung cancer. However, the conventional anti‑MUC1 antibody is not useful for the differentiation of malignant lung tumors and benign lesions due to its limited specificity. Our previous study screened a novel epitope‑defined antibody against cancer‑associated sugar chain structures that specifically recognizes the MUC1 Tn antigen (MUC1‑Tn ED Ab). In the present study, its potential utility as a diagnostic marker and therapeutic tool for lung adenocarcinoma (ADC) was examined. Immunohistochemical analysis of a lung ADC tissue microarray was performed using the MUC1‑Tn ED Ab (clone SN‑102), and the results were compared with those of another clone and commercially available MUC1 antibodies. The association between positive immunoreactivity of SN‑102 and clinicopathologic factors was analyzed. Furthermore, the association between MUC1‑Tn expression and epithelial‑mesenchymal transition markers and radiological characteristics was analyzed. Moderate or high MUC1‑Tn expression (MUC1‑Tn‑H) was observed in 138 (78.9%) of the 175 lung ADC cases. MUC1‑Tn‑H was associated with male sex, cigarette smoking, tumor extension, pleural invasion, and higher preoperative serum carcinoembryonic antigen and cytokeratin 19 fragment levels. Tumors with MUC1‑Tn‑H had higher consolidation/tumor ratios according to computed tomography and greater uptakes of 18F‑fluorodeoxyglucose. A total of 46 (26.9%) of the tumors had mesenchymal features, and MUC1‑Tn positivity was higher in the mesenchymal group than in the epithelial and intermediate groups (P<0.01 and P<0.01, respectively). Patients with tumors exhibiting MUC1‑Tn‑H had significantly shorter 5‑year overall and disease‑free survival times (P=0.011 and P<0.001, respectively). Additionally, MUC1‑Tn‑H was identified as an independent prognostic factor in multivariate analysis (P=0.024). MUC1‑Tn is specific for lung cancer cells and can improve diagnostic capabilities. Additionally, it may be a potential therapeutic target in lung ADC

CCR7 Mediates Cell Invasion and Migration in Extrahepatic Cholangiocarcinoma by Inducing Epithelial-Mesenchymal Transition

Simple Summary Extrahepatic cholangiocarcinoma (EHCC) is an aggressive tumor. The five-year survival rate for patients who undergo surgical resection is only 20-40% due to recurrences. Therefore, elucidating the molecular mechanisms underlying invasion and metastasis in EHCC is crucial for developing adjuvant therapy. The epithelial-mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in two EHCC cell lines. CCR7 mediates cell invasion and migration in EHCC by inducing EMT, which was abrogated by a CCR7 antagonist. CCR7 may be a potential target for adjuvant therapy in EHCC. The epithelial-mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (EHCC) remains unknown. This study aimed to elucidate the prognostic impact of CCR7 expression and its association with clinicopathological features and EMT in EHCC. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in TFK-1 and EGI-1 EHCC cell lines. High-grade CCR7 expression was significantly associated with a large number of tumor buds, low E-cadherin expression, and poor overall survival. TFK-1 showed CCR7 expression, and Western blotting revealed E-cadherin downregulation and vimentin upregulation in response to CCL19 treatment. The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC