title: Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.
abstract: Transmembrane tumor necrosis factor-α (tmTNF-α) is known to induce the activation of NF-κB to protect tumor cells. Upregulation of tmTNF-α leads to resistance to apoptosis and induces drug resistance in breast cancer. However, the expression of tmTNF-α in colorectal cancer (CRC) and its association with clinical outcome in CRC have remained unclear. In this study, we examined the tmTNF-α expression in CRC by immunohistochemistry and western blotting, assessed the prognostic value of tmTNF-α related to the recurrence/metastasis and survival of stage II/III CRC by the Kaplan-Meier survival curve and Cox regression model, and also explored the role of tmTNF-α expression on the chemotherapeutic efficacy of 5-Fluorouracil by flow cytometry assay and cell counting kit-8 (CCK-8) in vitro. Overall, we found that 77 (78.6%) out of 98 patients exhibited higher tmTNF-α expression in the CRC tissues comparing with the adjacent tissues. The tmTNF-α expression was correlated with Differentiation (P = 0.019), TNM stage (P = 0.039), Lymph nodes metastasis (P = 0.024) and Lymphovascular invasion (P = 0.027) but not related with Age (P = 0.617), Gender (P = 0.625), Tumor location (P = 0.138), Perforation/Obstruction (P = 1.000), Depth of invasion (P = 0.327), and microsatellite instability status (P = 0.150). The prognostic analyses showed that high tmTNF-α expression patients was significantly associated with decreased Disease-Free Survival (P = 0.0209) and Overall Survival (P = 0.0163). CCK-8 results suggested that the tmTNF-α influenced the chemotherapeutic effect of 5-Fluorouracil on colon cancer cells. Altogether, these data indicated the stageII/III CRC patients with high tmTNF-α expression were more likely to have a worse prognosis than patients with low tmTNF-α expression and tmTNF-α may influence the chemotherapeutic effect of 5-Fluorouracil. The mechanism for these observations warrants further study.
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Xiaogai
authors.initials: X
authors.lastname: Li
authors.affiliation: b Department of Clinical Laboratory , The First People's Hospital of Zhengzhou City , Zhengzhou , China.
authors.forename: Shihai
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: HuiJun
authors.initials: H
authors.lastname: Ren
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Junfen
authors.initials: J
authors.lastname: Ma
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Sun
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Cailin
authors.initials: C
authors.lastname: Liu
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Kaida
authors.initials: K
authors.lastname: Huang
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: a Department of Clinical Laboratory , The First Affiliated Hospital of Zhengzhou University & Key Clinical Laboratory of Henan Province.
authors.forename: Liang
authors.initials: L
authors.lastname: Ming
mesh_terms: D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008297:Male; D011379:Prognosis; D015398:Signal Transduction; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D005472:Fluorouracil
keywords: Colorectal cancer; prognosis; recurrence/metastasis; survival; tmTNF-α