Abstract
Colorectal cancer (CRC) is one of the most frequent malignant neoplasms worldwide, and the effect of treatments is limited. Fibroblast growth factor 1 (FGF1) has been involved in a wide variety of several malignant diseases and takes part in the tumorigenesis of CRC. However, the function and mechanism of FGF1 in CRC remains elusive. In this study, the results indicated that FGF1 is elevated in CRC tissues and linked with poor prognosis (P < 0.001). In subgroup analysis of FGF1 in CRC, regardless of any clinic-factors except gender, high level FGF1 expression was associated with markedly shorter survival (P < 0.05). In addition, the expression of p-S6K1 and FGF1 was not associated in normal tissue (P = 0.781), but their expression was closely related in tumor tissue (P = 0.010). The oncogenic role of FGF1 was determined using in vitro and in vivo functional assays. FGF1 depletion inhibited the proliferation and migration of CRC cells in vitro and vivo. FGF1 was also significantly correlated with mTOR-S6K1 pathway on the gene and protein levels (P < 0.05). In conclusion, FGF1 acts as a tumor activator in CRC, and against FGF1 may provide a new visual field on treating CRC, especially for mTORC1-targeted resistant patients.
Highlights
Colorectal cancer (CRC) is the second cause of cancer death in western countries
Fibroblast growth factor 1 (FGF1) expression was significantly associated with lymph node metastasis (P = 0.003), tumor budding degree (P = 0.002) and tumor−node −metastasis (TNM) stage (P = 0.001, Table 2), while no correlation was observed with other clinicopathological variables such as age, gender, tumor size, the depth of invasion, degree of differentiation, venous invasion and neural invasion (P > 0.05, Table 2)
To demarcated the patients according to FGF1 expression levels, we found the reduced FGF1 expression promoted prognosis in TCGA dataset searched by GEPIA platform (Figure 1E) and checked in 135 CRC tissues (Figure 1F)
Summary
Colorectal cancer (CRC) is the second cause of cancer death in western countries. Half of the CRC patients will die from the disease which is due to distant metastasis of the primary CRC [1, 2]. CRC is one of the most prevalent malignant tumors in China, with high incidence rate and mortality. Screening has been shown to be effective in reducing the incidence of, and mortality from CRC. A curative therapy to control the huge threat should include surgical and nonsurgical treatment. It is extremely urgent to identify effective biomarker for diagnosis and against target for treatment
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