Oesophageal squamous cell carcinoma (ESCC) is an aggressive malignancy and a leading cause of cancer-related death worldwide. Lack of effective early diagnosis strategies and ensuing complications from tumour metastasis account for the majority of ESCC death. Thus, identification of key molecular targets involved in ESCC carcinogenesis and progression is crucial for ESCC prognosis. In this study, four pairs of ESCC tissues were used for mRNA sequencing to determine differentially expressed genes (DEGs). 347 genes were found to be upregulated whereas 255 genes downregulated. By screening DEGs plus bioinformatics analyses such as KEGG, PPI and IPA, we found that there were independent interactions between KRT family members. KRT17 upregulation was confirmed in ESCC and its relationship with clinicopathological features were analysed. KRT17 was significantly associated with ESCC histological grade, lymph node and distant metastasis, TNM stage and five-year survival rate. Upregulation of KRT17 promoted ESCC cell growth, migration, and lung metastasis. Mechanistically, we found that KRT17-promoted ESCC cell growth and migration was accompanied by activation of AKT signalling and induction of EMT. These findings suggested that KRT17 is significantly related to malignant progression and poor prognosis of ESCC patients, and it may serve as a new biological target for ESCC therapy. SIGNIFICANCE: Oesophageal cancer is one of the leading causes of cancer mortality worldwide and oesophageal squamous cell carcinoma (ESCC) is the major histological type of oesophageal cancer in Eastern Asia. However, the molecular basis for the development and progression of ESCC remains largely unknown. In this study, RNA sequencing was used to establish the whole-transcriptome profile in ESCC tissues versus the adjacent non-cancer tissues and the results were bioinformatically analysed to predict the roles of the identified differentially expressed genes. We found that upregulation of KRT17 was significantly associated with advanced clinical stage, lymph node and distant metastasis, TNM stage and poor clinical outcome. Keratin 17 (KRT17) upregulation in ESCC cells not only promoted cell proliferation but also increased invasion and metastasis accompanied with AKT activation and epithelial-mesenchymal transition (EMT). These data suggested that KRT17 played an important role in ESCC development and progression and may serve as a prognostic biomarker and therapeutic target in ESCC.

Original Article Toripalimab combined with docetaxel and cisplatin neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a single-center, single-arm clinical trial (ESONICT-2) Lei Gao, Jieming Lu, Peipei Zhang, Zhi-Nuan Hong, Mingqiang Kang

Background: Esophageal cancer (EC) is a malignant tumor with high mortality. Correlations have been found between the expression level of tropomyosin 3 (TPM3) and the depth of tumor invasion, lymph node metastasis, and the 5-year survival rate. However, the specific mechanisms underlying EC remain unclear. Methods: Stably transfected TPM3-overexpresing and TPM3-knockdown esophageal squamous cell carcinoma (ESCC) cell lines (ECa109 and EC9706) were constructed, and the association between TPM3 and the proliferation, invasion, and migration of ESCC was investigated using molecular biology methods. The associations between TPM3 and matrix metalloproteinase (MMP)2/9 or epithelial-mesenchymal transition (EMT)-related proteins were verified, and the potential tumor-promoting mechanism was explored by Gelatin Zymography Experiment. Results: TPM3 was found to promote the proliferation, migration, and metastatic potential of ESCC in vivo and in vitro, and stimulate the expression of MMP2/9 and certain EMT markers other than E-cadherin. The replenishment of MMP2/9 restored the malignant behavior of ESCC caused by TPM3. A gelatinase assay showed that the expression of TPM3 was related to the activity of MMP9. Conclusions: TPM3 promoted proliferation, migration, and metastatic potential in EC cells. Additionally, TPM3 promoted the EMT process. This function may be achieved via the regulation the expression of MMP2/9.

Programmed death-1 polymorphisms is associated with risk of esophagogastric junction adenocarcinoma in the Chinese Han population: A case-control study involving 2,740 subjects Programmed death-1 polymorphisms is associated with risk of esophagogastric junction adenocarcinoma in the Chinese Han population: A case-control study involving 2,740 subjects