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Colorectal cancer (CRC) is a common digestive malignancy and emerging studies have closely linked its initiation and development with gut microbiota changes. Fusobacterium nucleatum (Fn) has been recently identified as a pathogenic bacteria for CRC; however, its prognostic significance for patients is poorly investigated and is less for patients within late stage. Therefore, in this study, we made efforts to analyze its level and prognostic significance in a retrospective cohort of 280 stage III/IV CRC patients. We found that the Fn level was abnormally high in tumor tissues and correlated with tumor invasion, lymph node metastasis status, and distant metastasis. We also identified it as an independent adverse prognostic factor for cancer-specific survival (CSS) and disease-free survival (DFS). The following subgroup analysis indicated that Fn level could stratify CSS and DFS in stage IIIB/C and IV patients but failed in stage IIIA patients. In addition, stage III/IV patients with low Fn level were found to benefit more from adjuvant chemotherapy than those with high Fn level, in terms of DFS. Finally, we analyzed the expression and clinical significance of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) and cancer stem cell (CSC) markers (Nanog, Oct-4, and Sox-2) in CRC tissues. The results indicated that N-cadherin, Nanog, Oct-4, and Sox-2 were adverse prognostic factors in these patients, while the opposite was true for E-cadherin. More importantly, expression of E-cadherin, N-cadherin, and Nanog was significantly correlated with Fn level in tumor tissues, suggesting the potential involvement of Fn in EMT-CSC cross talk during CRC progression. Taken together, these findings indicate that Fn is a novel predictive biomarker for clinical management in stage III/IV patients, and targeting Fn may be an effective adjuvant approach for preventing CRC metastasis and chemotherapy resistance.

Yuanjue Sun,1,* Liguo Liu,2,* Yaling Wang,3 Aina He,3 Haiyan Hu,3 Jianjun Zhang,3 Mingyong Han,1 Yujing Huang3 1Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 250021, Shandong, People’s Republic of China; 2Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 200233 Shanghai, People’s Republic of China; 3Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 200233 Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: The aims of this study were to determine the effect of curcumin on osteosarcoma (OS) cells due to inactivation of the p-JAK2/p-STAT3 pathway and evaluate the prognostic value of this pathway in OS. Materials and methods: We exposed a human OS cell line (MG-63) to different concentrations of curcumin. Then, we characterized the effects on MG-63 cells using assays (cell viability, colony formation, cell cycle, wound healing, invasion), flow cytometry, Western blot, immunohistochemical analyses, and tumor xenograft. Results: The half-maximal inhibitory of curcumin for MG-63 cells at 24 hours was 27.6 µM. The number of colonies of MG-63 cells was decreased obviously upon curcumin (10 and 20 µM) treatment. We also found increased accumulation of MG-63 cells in the G2/M phase upon curcumin (10 and 20 µM) treatment. Apoptosis was increased in 10 and 20 µM curcumin-treated MG-63 cells. After incubation of physically wounded cells for 24 hours, the percentage wound width increased upon curcumin exposure. Curcumin obviously decreased the expression of pJAK-2 and pSTAT-3 in MG-63 cells in a dose-dependent manner. Curcumin dose-dependently inhibited the proliferation, migration, and invasion of MG-63 cells and induced arrest of the G0/G1 phase and apoptosis by inhibiting the p-JAK2/p-STAT3 pathway. The linear correlativity between expression of p-JAK2 and STAT3 was very prominent, and both were closely associated with lung metastasis. In vivo study suggested that curcumin suppressed tumor growth through JAK2/STAT3 signaling. Conclusion: Curcumin-mediated inhibition of the proliferation and migration of MG-63 cells was associated with inactivation of JAK/STAT signaling. Keywords: osteosarcoma, curcumin, multiplication, invasion