RESUMO
The prognosis for pathologically node-negative (pN0) esophageal squamous cell carcinoma (ESCC) with surgery alone remains poor. We aimed to develop a model for a more precise prediction of recurrence, which will allow personalized management for pN0 ESCC after upfront complete resection. Clinical and pathological records of patients with completely resected pT1-3N0M0 ESCC were retrospectively analyzed between January 2014 and December 2019. A nomogram for the prediction of recurrence was established based on the Cox regression analysis and evaluated by C-index, AUC, and calibration curves. The model was further validated using bootstrap resampling and k-fold cross-validation and compared with the 8th edition of the AJCC TNM staging system using Td-ROC, NRI, IDI, and DCA. Two-hundred-and seventy cases were included in this study. The median follow-up was 45 months. Distant and/or loco-regional recurrences were noted in 89 (33.0%) patients. The predictive model revealed pT-category, differentiation, perineural invasion, examined lymph nodes (ELN), and prognostic nutritional index (PNI) as independent risk factors for recurrence, with a c-index of 0.725 in the bootstrapping cohort. Td-ROC, NRI, and IDI showed a better predictive ability than the AJCC 8th TNM staging system. Based on this model, patients in the low-risk group had a significantly lower recurrence incidence than those in the high-risk group (p < .001). The predictive model developed in this study may facilitate the precise prediction of recurrences for pN0 ESCC after upfront surgery. Stratifying management of those patients might bring significantly better survival benefits.
RESUMO
BACKGROUND: Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). METHODS: The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. RESULTS: ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. CONCLUSIONS: ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.
