Cervical cancer has the second-highest incidence and mortality of female malignancy. The major causes of mortality in patients with cervical cancer are invasion and metastasis. The epithelial–mesenchymal transition (EMT) process plays a major role in the acquisition of metastatic potential and motility. Autophagy-related genes (ARGs) are implicated in the EMT process, and autophagy exerts a dual function in EMT management at different phases of tumor progression. However, the role of specific ARGs during the EMT process has not yet been reported in cervical cancer. Based on the data from the Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) sequencing database, we performed the prognosis analysis for those ARGs obtained from the Human Autophagy database. ATG5 was identified as the only important harmful marker influencing survival of cervical cancer patients by univariate Cox regression (HR 1.7; 95% CI: 1.0–2.8, p = 0.047), and the 5-years survival rate for the high- and low-ATG5 expression groups was 0.486 (0.375–0.631) and 0.782 (0.708–0.863), respectively. TCGA CESC methylation data showed that eight methylation sites of ATG5 could also be significantly associated with the overall survival (OS) of cervical cancer patients. Single-sample gene-set enrichment and gene functional enrichment results showed that ATG5 was correlated with some cancer-related pathways, such as phagocytosis-related genes, endocytosis-related genes, immune-related genes, EMT score, and some EMT signature-related genes. Next, cell migration and invasion assay and Western blot were applied to detect the function of ATG5 in EMT of cervical cancer. In cervical cancer cells, ATG5 knockdown resulted in attenuation of migration and invasion. The functional study showed that knockdown of ATG5 could reverse EMT process by P-ERK, P-NFκBp65, P-mTOR pathways, and so on. In conclusion, the present study implies that ATG5 was a major contributor to EMT regulation and poor prognosis in cervical cancer.

PH domain Leucine-rich-repeats protein phosphatase (PHLPP) is a novel family of Ser/Thr protein dephosphatases that play a critical role in maintaining the balance in cell signaling. PHLPP negatively regulates PI3K/Akt and RAF/RAS/′ signaling activation, which is crucial in development, growth, and proliferation of lung cancer. The aim of this study was to investigate the association of PHLPP expression with biological behavior and prognosis of lung adenocarcinoma. One hundred and fifty eight patients with pathologically documented stage I, II or IIIA lung adenocarcinoma were recruited in this study. Expression of PHLPP, p-AKT and p-ERK were evaluated by immunohistochemistry (IHC) in paraffin-embedded resected specimens. The correlation of their expression, which was dichotomized to low expression (a score of 0, 1) versus high expression (a score of 2, 3), with the clinicopathological parameters and prognosis of the patients also analyzed. High PHLPP expression rate in lung adenocarcinoma was 23.4 %. PHLPP expression level was significantly associated with tumor differentiation (p = 0.025) and tumor stage (p = 0.024). Patients with high expression of PHLPP showed significantly longer average survival time and higher 3 years survival rate than those with low expression of PHLPP (45 months versus 38 months, 85.8 % versus 73.5 % respectively) (Log rank test x2 = 7.086, p =0.008). A significant inverse correlation was observed between PHLPP expression and p-AKT (r = −0.523, p = 0.000) or p-ERK (r = −0.530, p = 0.000). Our results suggest that high levels of PHLPP might reflect a less aggressive lung adenocarcinoma phenotype and predict better survival in patients with lung adenocarcinoma. PHLPP can be a potential prognostic marker to screen patients for favorable prognoses.

To determine the position and dose delivery changes rules of parotid gland (PG) during the course of intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma patients (NPC). One hundred and forty one competed tomography (CT) images from 47 NPC patients (three images for each patient were acquired before treatment, at the 15th and 25th fraction during the treatment) who underwent radical IMRT were selected for this study. A total of 70-76Gy at 2.12–2.3 Gy/fraction/d was given to the GTVnx in 33 fractions. The distances between the lateral/medial aspects of PG and midline (DLM and DMM) at the level of odontoid process were measured. The dose differences between plan and actual delivery were calculated. The volume reductions of PGs between fractions 15 and 25 were larger than those in the first 15 fractions (4.68 ± 3.23 cc vs. 2.46 ± 4.55 cc for the right PG and 5.96 ± 2.99 cc vs. 2.06 ± 2.99 cc for the left PG). However, the percentage of gland volume receiving ≥30 Gy (V30) of bilateral PGs decreased more significantly in the first 15 fractions than that between fractions 15 and 25 (5.61 ± 16.04% vs. 1.14 ± 21.54% for the right PG and 6.87 ± 15.58% vs. 0.81 ± 15.94% for the left PG). The gross tumor volume of the nasopharynx (GTVnx) decreased more significantly in the first 15 fractions than that between the 15th and 25th fraction (8.23 ± 13.61 cc vs. 3.30 ± 8.09 cc). The DMM of ipsilateral PGs reduced in the first 15 fractions (0.80 ± 2.96 mm) but increased between fraction 15 and 25 (−2.19 ± 3.96 mm). While ipsilateral PG shifted into target volume but shifted out target volume between fraction 15 and 25. Parotid glands V30 was correlated with GTVnx, GTVnx reduction and DMM reduction (p < 0.01). Our results indicate that the reduction of GTVnx leads to the positional change of the parotid gland, which results in more significant dose change of the parotid gland in the first 15 fractions than that between fraction 15 and 25.

Corrigendum: Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma