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Background Urothelial carcinoma (UC) is among the most prevalent malignancies. The muscle-invasive bladder cancer (MIBC) shows an invasive feature and has poor prognosis, while the non-muscle invasive bladder cancer (NMIBC) shows a better prognosis as compared with the MIBC. However, a significant proportion (10%–30%) of NMIBC cases progress to MIBC. Identification of efficient biomarkers for the prediction of the course of UC remains challenging nowadays. Recently, there is an emerging study showed that post-translational modifications (PTMs) by glycosylation is an important process correlated with tumor angiogenesis, invasion and metastasis. Herein, we reported a data-driven discovery and experimental validation of GANAB, a key regulator of glycosylation, as a novel prognostic marker in UC. Methods In the present study, we conducted immunohistochemistry (IHC) assay to evaluate the correlation between the expression levels of GANAB protein and the prognosis of UC in our cohort of 107 samples using whole slide image (WSI) analysis. In vitro experiments using RNAi were also conducted to investigate the biological functions of GANAB in UC cell lines. Results We observed that positive GANAB protein expression was significantly correlated with poor prognosis of UC in our cohort, with p-value of 0.0017 in Log-rank test. Notably, tumor cells at the invasive front of the tumor margin showed stronger GANAB expression than the tumor cells inside the tumor body in UCs. We further validated that the elevated expression levels of GANAB were significantly correlated with high grade tumors (p-values of 1.72 × 10–10), advanced stages (6.47 × 10–6), and elevated in luminal molecular subtypes. Moreover, knocking-down GANAB using RNAi in UM-UC-3 and T24 cells inhibited cell proliferation and migration in vitro. Knockdown of GANAB resulted in cell cycle arrest at G1 phase. We demonstrated that GANAB mediated HIF1A and ATF6 transcriptional activation in the ER stress signaling, and regulated the gene expression of cell cycle-related transcriptional factors E2F7 and FOXM1. Conclusions The elevated expression of GANAB is a novel indicator of poorer prognosis of UC. Our data suggests that GANAB is not only a new and promising prognostic biomarker for UC, but also may provide important cues for the development of PTM-based therapeutics for UC treatment.

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BackgroundHuman papillomavirus (HPV) infection is the main pathogen of precancerous transformation and finally progress to cervical cancer. It associated with cervical squamous and glandular lesions. However, the genotype distribution of HPV and the relationship between HPV infection and cervical disease are still remind unclear.Material and methodsA total of 7391 abnormal cervical cytology cases with detailed histological reports and HPV genotypes were collected. The prevalence of HPV infection in squamous epithelial lesions and glandular epithelial lesions were statistically analyzed.ResultAround 6958 cytological squamous epithelial lesions and 433 glandular epithelial lesions were enrolled. 79.72% of cytological squamous epithelial lesions and 26.56% of glandular epithelial lesions were HPV infected. The HPV infection rates in squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma were 66.67%, 54.17% and 19.72%, respectively. HVP16, 18 and 58 are the most common types in squamous and glandular epithelial lesions. Among the squamous epithelial lesions, women less than 25 years old had the highest HPV infection rate, and majority of multiple infections was found in women >55 years old. The total infection rate of HPV in glandular epithelial lesions was the highest in the 35 to 45 group. Multiple infections peaked in women around 55 years old.ConclusionThe prevalence of HPV infection is divergent in different types of cervical cancer. The HPV infections in cervical squamous epithelial lesions tended to be younger. HPV detection is one of the necessary tests for cervical disease screening and should be individualized in an age manner.