Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

Mitsunari, Kensuke; Miyata, Yasuyoshi; Watanabe, Soichi; Asai, Akira; Yasuda, Takuji; Kanda, Shigeru; Sakai, Hideki

doi:10.3892/ol.2016.5481

Cited by 7 publications

(5 citation statements)

References 42 publications

(51 reference statements)

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“…FER is widely recognized as an oncogene that promotes cancer cell metastasis, proliferation, survival, metabolic plasticity, mitochondrial homeostasis, and drug resistance(60-64). However, a study have also implicated FER as a TSG, with a positive correlation between low FER expression and increased malignancy and poor prognosis in renal cell carcinoma (15). We observed that patients with low FER expression had a shorter survival time and that their tumor tissues were characterized by more prominent malignant molecular characteristics, including high metabolism, low cell adhesion, and stem cell-like properties.…”

Section: Discussionmentioning

confidence: 57%

“…However, the role of FER in tumor remains unclear. Decreased FER expression can impede the growth of pancreatic and colon cancer cells (13,14), whereas this gene is also positively associated with the tumor progression and metastasis of renal cell carcinoma (15). Therefore, the functions and mechanisms of FER in tumor initiation and progression require further investigation.…”

Section: Introductionmentioning

confidence: 99%

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An in vivo genome-wide CRISPR-Cas9 screen identifies FER as a tumor suppressor inhibiting the oncogenic transformation

Wang

Zhang

et al. 2023

Preprint

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Background Tumorigenesis is a complex and multistep process characterized by the progressive acquisition of various hallmarks, including unlimited proliferation, resistance to apoptosis, and increased invasiveness and metastasis. However, the molecular mechanisms underlying tumorigenesis remain poorly understood. Methods An in vivo genome-wide CRISPR–Cas9 screen was employed to identify tumor suppressor genes (TSG). The expression correlation analysis for candidate TSGs was performed in normal and cancer cells using TCGA database. To evaluate the role of FER in tumorigenesis, we firstly used publicly single-cell RNA sequencing data to investigate the association of FER expression and normal cell malignant transformation. Next, we established FER-knockout and -knockdown models in BEAS-2B and MCF10A cell lines. Colony formation assay, cell proliferation assay, EdU assay and apoptosis assay were conducted to determine the role of FER in tumorigenesis. Then RNA-seq was performed to explore the mechanism underlying the role of FER in inhibiting tumorigenesis. Additionally, Pan-Cancer analysis was used to analysis the role of FER in tumor progression. Results In our CRISPR–Cas9 screen, we identified 20 candidate genes, among which FER exhibited the strongest negative correlation with tumorigenesis. Normal cells with low FER expression exhibited elevated malignant transformation potential and stemness properties. FER knockout promoted the tumorigenesis of differentiated epithelial cells by reprogramming them into a cancer stem cell (CSC)-like state, characterized by high colony-forming efficiency and suspension growth ability, increased metabolic activity, dedifferentiation properties, and immune evasion. Furthermore, tumors with low FER expression exhibited poor prognosis and a noticeable CSC-like state. Conclusion Taken together, our findings not only provide insights into the essential role of FER as a stemness barrier in malignant cells during tumor initiation and progression but also highlight its potential as a target for future clinical diagnosis.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

An in vivo genome-wide CRISPR-Cas9 screen identifies FER as a tumor suppressor inhibiting the oncogenic transformation

Wang

Zhang

et al. 2023

Preprint

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“…Besides, low expression of some genes (e.g., Fer) in stromal cells is related to increased malignant aggressiveness and decreased survival rate in RCC patients. [ 42 ] As far as we know, this is the first study to construct a nomogram integrated immune scores and clinicopathological factors for predicting the prognosis of ccRCC patients. The area under the curve of ROC curves and c-index value revealed that the immune scores-based nomogram for 3- and 5-year OS had good predictive value.…”

Section: Discussionmentioning

confidence: 99%

An immune scores-based nomogram for predicting overall survival in patients with clear cell renal cell carcinoma

Ouyang²,

Peng

2020

Medicine

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The role of immune cell infiltration in the prognosis of clear cell renal cell carcinoma (ccRCC) has received increasing attention. However, immune scores have not yet been introduced into routine clinical practice of ccRCC patients. The principal objective of our research was to study the correlation between immune scores and overall survival (OS) of ccRCC. In this study, Cox regression analyses were used to identify risk factors associated with OS of ccRCC based on the Cancer Genome Atlas datasets. Furthermore, an integrated nomogram combining immune scores and clinicopathologic factors was built for predicting 3- and 5-year OS of ccRCC patients. The receiver operating characteristic curve, concordance index, and calibration curves were used for the evaluation of our nomogram. Also, Kaplan–Meier (KM) survival analysis of immune scores, stromal scores, and different clinicopathological factors was performed. A total of 514 patients were divided into the low- or high-immune scores group. KM and multivariate Cox regression analyses demonstrated that ccRCC patients with high-immune scores had significantly poor OS compared with those with low-immune scores. Calibration curves showed good consistency between the predicted OS and the actual OS probability. Areas under the receiver operating characteristic curves for 3- and 5-year OS were 0.816 and 0.769, and the concordance index was 0.775, indicating that our nomogram had good accuracy for predicting OS of ccRCC patients. Additionally, KM analysis showed that older age, later T stage, distant metastasis, advanced tumor lymph node metastasis stage, higher tumor grade, left site, and low stromal scores were associated with worse OS in ccRCC patients. High-immune scores show a significant correlation with unsatisfactory prognosis in ccRCC patients. Furthermore, the immune scores-based nomogram may be helpful in predicting ccRCC prognosis.

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“…Slides were examined using a computer-aided image analysis system (Win ROOF version 5.0; MITANI, Fukui, Japan), and were scored twice at different times by TM and YM, who were blinded to the clinicopathological and survival data. Detailed methods of the immunohistochemical techniques, including negative and positive controls, have been described in our previous reports (2,11,25,26).…”

Section: Methodsmentioning

confidence: 99%

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

Harada

Miyata

Araki

et al. 2021

In Vivo

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Background/Aim: The pathological significance of thrombospondin (TSP)-1 and -2 in bladder cancer (BC) is well-known whereas that of 4 and 5 remains unclear. Our aim is to clarify the pathological significance and prognostic roles of TSP-3 to 5 expression in BC patients. Patients and Methods: TSP-3 to 5 expression, proliferation index (PI), apoptotic index (AI) and microvessel density (MVD) were evaluated in 206 BC patients by immunohistochemical techniques. Results: TSP-5 expression was positively associated with grade, T stage, metastasis, and worse prognosis. PI in TSP-5-positive tissues was significantly higher compared to negative tissues. In contrast, AI in TSP-5-positive tissues was significantly lower compared to negative tissues. Expressions of TSP-3 and 4 were not associated with any clinicopathological features, survival, PI, or AI. Conclusion: TSP-5 plays important roles in malignant behavior via cell survival regulation whereas the pathological significance of TSP-3 and TSP-4 in BC might be minimal.

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Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival

Cited by 7 publications

References 42 publications

An in vivo genome-wide CRISPR-Cas9 screen identifies FER as a tumor suppressor inhibiting the oncogenic transformation

An in vivo genome-wide CRISPR-Cas9 screen identifies FER as a tumor suppressor inhibiting the oncogenic transformation

An immune scores-based nomogram for predicting overall survival in patients with clear cell renal cell carcinoma

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

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