Aberrant activation of the Wnt/β-catenin pathway is frequent in hepatocellular carcinoma (HCC) and contributes to HCC initiation and progression. This abnormal activation may result from somatic mutations in the genes of the Wnt/β-catenin pathway and/or dysregulation of the Wnt/β-catenin pathway. The mechanism for the latter remains poorly understood. Prospero-related homeobox 1 (PROX1) is a downstream target of the Wnt/β-catenin pathway in human colorectal cancer and elevated PROX1 expression promotes malignant progression. However, the Wnt/β-catenin pathway does not regulate PROX1 expression in the liver and HCC cells. Here we report that PROX1 promotes HCC cell proliferation in vitro and tumor growth in HCC xenograft mice. PROX1 and β-catenin levels are positively correlated in tumor tissues as well as in cultured HCC cells. PROX1 can upregulate β-catenin transcription by stimulating the β-catenin promoter and enhance the nuclear translocation of β-catenin in HCC cells, which leads to the activation of the Wnt/β-catenin pathway. Moreover, we show that increase in PROX1 expression renders HCC cells more resistant to sorafenib treatment, which is the standard therapy for advanced HCC. Overall, we have pinpointed PROX1 as a critical factor activating the Wnt/β-catenin pathway in HCC, which promotes HCC proliferation and sorafenib resistance.

The aim of this study was to distinguish and compare the chest imaging features of non-tuberculous mycobacteria lung disease (NTM-LD) and pulmonary tuberculosis (PTB) in patients with sputum acid fast bacillus (AFB)-smear positive since an earlier differential diagnosis between these two is very important in clinical practice. PATIENTS AND METHODS: A total of 4167 previously untreated cases with AFB smear-positive sputum were collected from January 2011 to January 2014, in Shanghai Pulmonary Hospital, Tongji University, China. Among them, 124 cases were identified with NTM-LD after specimen culture and strain identification. A cohort of 210 patients with PTB was randomly selected from the remaining 4043 cases with PTB as comparator. The clinical and chest computed tomography (CT) imaging data were compared. RESULTS: The most prevalent pathogens in patients with NTM-LD were Mycobacterium abscessus (42%, 52/124) and Mycobacterium intracellulare (34%, 42/124). Univariate analysis showed patients with NTM-LD more frequently had bronchiectasis (85.5% vs. 45.7%, p < 0.001), thin-walled cavity (D ≥ ≥ 3 cm) (16.9% vs. 7.6%, p = 0.011) compared to PTB patients. Additionally, the location of lesion also differed and the right middle lobe (23.9% vs. 16.3%, p < 0.001) and left lingual segment bronchiectasis (19.9% vs. 8.2%, p < 0.001) were more prominent in NTM-LD. Multivariate analysis showed, bronchiectasis (OR = 8.521, 95% CI: 4.209-17.250, p < 0.001) and thinwalled cavity (D ≥ ≥ 3 cm) (OR = 3.561, 95% CI: 1.394-9.097, p = 0.008) were also the independent predictors for the diagnosis of NTM-LD. CONCLUSIONS: Bronchiectasis in the right middle lobe or left lingual segment and thinwalled cavity with a diameter of more than 3 cm are the frequently the chest CT features in patients with NTM-LD, which might be helpful for an early diagnosis in patients with AFB-smear positive.