Background: Metastasis and recurrence, wherein circulating tumour cells (CTCs) play an important role, are the leading causes of death in colorectal cancer (CRC). Metastasis-initiating CTCs manage to maintain intravascular survival under anoikis, immune attack, and importantly shear stress; however, the underlying mechanisms remain poorly understood. Methods: In view of the scarcity of CTCs in the bloodstream, suspended colorectal cancer cells were flowed into the cyclic laminar shear stress (LSS) according to previous studies. Then, we detected these suspended cells with a CK8+/CD45−/DAPI+ phenotype and named them mimic circulating tumour cells (m-CTCs) for subsequent CTCs related researches. Quantitative polymerase chain reaction, western blotting, and immunofluorescence were utilised to analyse gene expression change of m-CTCs sensitive to LSS stimulation. Additionally, we examined atonal bHLH transcription factor 8 (ATOH8) expressions in CTCs among 156 CRC patients and mice by fluorescence in situ hybridisation and flow cytometry. The pro-metabolic and pro-survival functions of ATOH8 were determined by glycolysis assay, live/dead cell vitality assay, anoikis assay, and immunohistochemistry. Further, the concrete up-anddown mechanisms of m-CTC survival promotion by ATOH8 were explored. Results: The m-CTCs actively responded to LSS by triggering the expression of ATOH8, a fluid mechanosensor, with executive roles in intravascular survival and metabolism plasticity. Specifically, ATOH8 was upregulated via activation of VEGFR2/AKT signalling pathway mediated by LSS induced VEGF release. ATOH8 then transcriptionally activated HK2-mediated glycolysis, thus promoting the intravascular survival of colorectal cancer cells in the circulation. Conclusions:This study elucidates a novel mechanism that an LSS triggered VEGF-VEGFR2-AKT-ATOH8 signal axis mediates m-CTCs survival, thus providing a potential target for the prevention and treatment of hematogenous metastasis in CRC.

Background The prognosis of patients under existing neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy requires improvement. Whereas programmed cell death 1 (PD-1) inhibitors have shown promising response in advanced esophageal cancer, they have not been used in the perioperative treatment of resectable locally advanced esophageal cancer. Whether immunotherapy can be incorporated into neoadjuvant therapy has became a challenging question for researchers. Case presentation We present a case of a 65-year-old male who had a history of progressive dysphagia for approximately 1 month. He underwent pertinent studies including computed tomography (CT)，gastroscopy，and pathological biopsy resulting in a diagnosis of medium-low differentiated squamous carcinoma of the thoracic segment of the esophagus (cT2N2M0 stage III). After 4 cycles of neoadjuvant chemotherapy combined with immunotherapy, gastroscopy showed the lesion in the esophagus was no longer present. Subsequently, the patient received thoracoscopic radical resection of esophageal cancer and achieved a pathological complete response (pCR) in postoperative pathological evaluation. During the whole treatment, no adverse effect was recorded and to date no evidence of recurrence has been recorded. Conclusion Our report suggest that neoadjuvant chemotherapy combined with immunotherapy not only improve the R0 resection and pCR rate in patients with resectable locally advanced esophageal cancer, but also the adverse effects are within the control range. However, the selection of therapeutic strategy, predictors of response to treatment, and interval time between neoadjuvant treatment and surgery still await more reliable evidence-based studies with large prospective samples.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with poor prognosis. Therefore, it is imperative to develop new prognostic or therapeutic biomarkers for TNBC. Objective: To explore the prognostic and therapeutic values of autophagy-related genes (ARGs) in TNBC. Methods: Overall, 157 TNBC patients’ data were obtained from The Cancer Genome Atlas database, and the ARGs were acquired from the Human Autophagy Database. Differentially expressed ARGs (DEGs) between tumor and normal tissues were identified and the prognostic ARGs were developed using R software. Kaplan–Meier survival curves and receiver operating characteristic (ROC) curves were both used to evaluate the accuracy of the signature. Patents about prognostic ARGs were reviewed through Worldwide Espacenet® and Patentscope®. Results: We obtained 28 DEGs and two prognostic ARGs (EIF4EBP1 and PARP1). The Kaplan–Meier survival curves showed that the survival rate of patients with low 2-ARG signature risk score was significantly higher than that of patients with high risk score (P=0.003). ROC at 5 years indicated that the signature had good prognostic accuracy (AUC=0.929). The signature was independent of T, N, M, and TNM stage (P<0.05). Patent review suggested that many mTOR inhibitors alone or in combination with another anticancer agent have been provided for treatment of many cancers and shown promising results. No drug patents about PARP1 overexpression were disclosed. Conclusion: We developed a 2-ARG signature (EIF4EBP1 and PARP1) which was an independent prognostic biomarker for TNBC. As EIF4EBP1 was upregulated in TNBC, mTOR inhibitors which blocked the mTOR/4EBP1/eIF4E pathway may be a promising therapeutic strategy for TNBC.

Objective. To investigate the association of the plasma level of cytokines and blood routine indexes with clinical characteristics in patients with cancer. Methods. We analyzed plasma samples derived from 134 cancer patients. Interleukins (IL) 1β, 2, 4, 5, 6, 8, 10, 12p70, 17, IFN-c, IFN-α, and TNF-α, and blood routine indexes were measured. e associations of the levels of cytokine and blood routine indexes with demographic and clinical characteristics of cancer patients were analyzed. Partial least-squares discriminant analysis was employed to identify cancer metastasis using these plasma cytokine metrics as input. We compared the predictive e ectiveness of numeric machine learning algorithms using these indexes and showed a promising model implemented with random forest. Results. Plasma levels of IL-6 and IL-8 in cancer patients with metastases were higher than those without metastases (P < 0.05). Cancer patients without metastases had signi cantly higher levels of plasma IL-12p70 and percentage of lymphocytes as compared with those with metastases (P < 0.05). Our random forest model showed the highest prediction performance (upper quantile AUC, 0.885) among the six machine learning algorithms we evaluated. Conclusion. Our ndings suggest that plasma levels of IL-6, IL-8, and IL-12p70 and the percentage of lymphocytes could predict the recurrence, metastasis, and progression of cancer. Our ndings will provide guidance for tumor monitoring and treatment.