The role of fibroblast growth factor 18 in cancers: functions and signaling pathways.

Fibroblast growth factor 18(FGF18) is a member of the fibroblast growth factor family (FGFs). FGF18 is a class of bioactive substances that can conduct biological signals, regulate cell growth, participate in tissue repair and other functions, and can promote the occurrence and development of different types of malignant tumors through various mechanisms. In this review, we focus on recent studies of FGF18 in the diagnosis, treatment, and prognosis of tumors in digestive, reproductive, urinary, respiratory, motor, and pediatric systems. These findings suggest that FGF18 may play an increasingly important role in the clinical evaluation of these malignancies. Overall, FGF18 can function as an important oncogene at different gene and protein levels, and can be used as a potential new therapeutic target and prognostic biomarker for these tumors.

Prediction of liver and lung metastases in patients with early-onset colorectal cancer by nomograms based on heterogeneous and homogenous risk factors.

BACKGROUND: Identifying the risk factors for distant metastasis in early-onset colorectal cancer (EOCRC) is crucial for elucidating its etiology and facilitating preventive treatment. This study aims to characterize the variability in EOCRC incidence and discern both heterogeneous and homogeneous risk factors associated with synchronous liver, lung, and hepato-lung metastases. METHODS: This study included patients with EOCRC enrolled in the SEER database between 2010 and 2015 and divided patients into three groups by synchronous liver, lung, and hepato-lung metastases. Each group of patients with different metastasis types was randomly assigned to the development and validation cohort in a ratio of 7:3. Logistic regression was used to analyze the heterogeneous and homogenous risk factors for synchronous liver, lung, and hepato-lung metastases in the development cohort of patients. Nomograms were built to calculate the risk of metastasis, and the receiver operating characteristic (ROC) curve and calibration curve were used to quantitatively evaluate their performance. RESULTS: A total of 16,336 eligible patients with EOCRC were included in this study, of which 17.90% (2924/16,336) had distant metastases. The overall incidences of synchronous liver, lung, and hepato-lung metastases were 11.90% (1921/16,146), 2.42% (390/16,126), and 1.50% (241/16,108), respectively. Positive CEA values before treatment, increased lymphatic metastases, and deeper invasion of intestinal wall were positively correlated with three distant types of metastases. On the contrary, the correlation of age, ethnicity, location of primary tumor, and histologic grade among the three types was inconsistent. The ROC curve and calibration curve proved to have fine performance in predicting distant metastases of EOCRC. CONCLUSIONS: There are significant differences in the incidence of distant metastases in EOCRC, and related risk factors are heterogeneous and homogenous. Although limited risk factors were incorporated in this study, the established nomograms indicated good predictive performance.

Prediction values of tertiary lymphoid structures in the prognosis of patients with left- and right-sided colon cancer: a multicenter propensity score-matched study.

BACKGROUND: Tertiary lymphoid structures (TLS) are the lymphocyte aggregates that play a key role in the vast majority of solid tumors including colon cancer, displaying an antitumor effect under most circumstances. The heterogeneity between left- and right-sided colon cancer (LCC and RCC) encompasses various aspects, such as clinical manifestations, pathological features, and immune responses. However, the function and prognostic significance of TLS within LCC and RCC have yet to be fully understood. METHODS: A retrospective analysis was performed on 2612 patients who underwent radical resection for LCC or RCC without distant metastasis in multiple medical centers. Utilizing propensity score matching, 121 patients with LCC and 121 patients with RCC were selected for the training set. An external validation set including 64 patients with LCC and 64 patients with RCC were also employed. Hematoxylin-eosin and immunohistochemical staining were used to assess TLS and the proportion of various immune cells. Clinical characteristics and prognostic values of TLS in patients with LCC and RCC were analyzed. Nomograms were constructed for LCC and RCC to predict 3-year and 5-year overall survival (OS), respectively. RESULTS: For LCC and RCC patients, TLS was located in the interstitial region or outside the tumor tissue and mainly consisted of B cells and T cells. The TLS quantity and density in RCC were higher than those of LCC. In multivariate Cox regression analysis, TLS density ( P =0.014), vascular invasion ( P =0.019), and AJCC stage ( P =0.026) were independent prognostic factors for 5-year OS of RCC. For LCC patients, AJCC stage ( P =0.024), tumor differentiation ( P =0.001), and tumor budding ( P =0.040) emerged as independent prognostic factors for 5-year OS. Similar results were obtained in the external verification set. Separate nomograms for RCC and LCC were developed, displaying improved prediction performance compared to the AJCC 8th edition TNM staging system. CONCLUSIONS: Differences in TLS quantity and density were observed between LCC and RCC, suggesting that a nomogram based on TLS density could more effectively predict survival for RCC patients. Furthermore, a nomogram based on tumor budding was recommended for better prediction of LCC patient survival. Taken together, these results suggested that the immune and clinical characteristics of colon cancer at left and right side were substantially different, which may lead to the use of different prediction model and the development of individual treatment strategy.