MUC1 in lung adenocarcinoma: cross-sectional genetic and serological study

Abstract

BackgroundMucin 1 (MUC1) contributes to the growth and metastasis of various cancers, including lung cancer, and MUC1 gene length polymorphisms are associated with susceptibility to lung cancer and its prognosis. In contrast, the association between rs4072037, a single nucleotide polymorphism in MUC1, and lung cancer has not been well studied.MethodsIn the present study, we determined the rs4072037 genotype and measured serum KL-6 levels to evaluate the association between lung adenocarcinoma (ADC) and rs4072037 or serum KL-6 levels. DNA samples were available for 172 patients and these were included in the genomic analyses. In addition, 304 patients were included in the serum analyses. Furthermore, 276 healthy volunteers were included in both genomic and serum analyses.ResultsThe rs4072037 genotype was not associated with susceptibility to lung ADC or its prognosis. Interestingly, serum KL-6 levels significantly differed according to rs4072037 genotype in those with T1 or T2 (P < 0.001), N0 or N1 (P = 0.002) and M0 (P < 0.001), but not in those with T3 or T4 (P = 0.882), N2 or N3 (P = 0.616) and M1a or M1b (P = 0.501). Serum KL-6 levels were significantly associated with the presence of lung ADC, as well as with its progression and prognosis, indicating the crucial involvement of KL-6/MUC1 in the development of lung cancer and its progression.ConclusionBased on these findings, we conclude that rs4072037 does not have a significant impact on the pathogenesis or prognosis of lung ADC, whereas serum KL-6 levels, which might reflecting the molecular length of MUC1, are significantly associated with lung ADC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3272-y) contains supplementary material, which is available to authorized users.

In vitro vascularized immunocompetent patient-derived model to test cancer therapies

“…Histological analyses confirmed that these three patients were lung adenocarcinomas ( Table S1 ). Different biomarkers confirmed the general equivalence of primary biopsy and vascularized PDTs, and hence the good overall reliability of the proposed model: TTF-1, 29 cytokeratin-7 (CK-7 or KRT7), 30 and mucin-1 (MUC-1) 30 for lung adenocarcinoma-associated markers and Ki-67 for cell proliferation ( Figure 2 , See also Figure S1 ). Besides those typical lung adenocarcinoma-associated markers, we also checked for epithelial to mesenchymal transition markers, such as the expression of vimentin or the loss of E-cadherin.…”

Vascularized patient-derived tumoroids supplemented with immune cells to predict response towards treatment for lung cancer patients

“…1). For memory, TTF-1 is a marker for epithelial-mesenchymal transition, used concomitantly with Ki-67, a marker of cell proliferation 22 , and with cytokeratin-7, and mucin-1, as predictive markers of tumor growth and metastasis 23,24 . All samples were negative for p40, the sensitive and speci c marker for distinguishing lung squamous cell carcinoma from adenocarcinoma.…”

Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration

“…Similarly, oncogene activated AT2s show disorganized apical domains, increasingly becoming unipolar at later stages, suggesting that the multi-apical polarity of AT2s is dynamically regulated in normal as well as disease states. Indeed, genetic mutations or altered expression of MUC1 has been implicated in lung cancer growth, metastasis, and chemotherapy resistance ( Bouillez et al., 2016 ; Ham et al., 2016 ; Horimasu et al., 2017 ; Raina et al., 2011 ; Saltos et al., 2018 ). In sum, our study has uncovered a unique multi-apical polarity of an epithelial cell type and its dynamics during development, injury repair, and tumorigenesis.…”