Prognostic value of programmed death‐ligand 1 expression in patients with stage <scp>III</scp> colorectal cancer

Koganemaru, Shigehiro; Inoshita, Naoko; Miura, Yuji; Miyama, Yu; Fukui, Yudai; Ozaki, Yukinori; Tomizawa, Kenji; Hanaoka, Yutaka; Toda, Shigeo; Suyama, Koichi; Tanabe, Yuko; Moriyama, Jin; Fujii, Takeshi; Matoba, Shuichiro; Kuroyanagi, Hiroya; Takano, Toshimi

doi:10.1111/cas.13229

Cited by 53 publications

(59 citation statements)

References 41 publications

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“…Therefore, we used the FAHZUSM cohort, a larger patient cohort complete with pathological tumor samples, to further study the expression of RON and PD-L1 in colorectal cancer tissues and to determine the pathological significance of elevated RON and PD-L1 expression in TC and in the cells of the tumor microenvironment.Dysregulation of RON and PD-L1 signal transduction is a key feature of many tumors. Our results and previous studies demonstrate that high expression of RON or PD-L1 in CRC tumor tissues correlates with the extent of primary tumor, lymph node metastasis, and distant metastasis(39,40). Furthermore, high expression of RON or PD-L1 in the tumor microenvironment was associated with poor survival in CRC patients(22,(39)(40)(41)(42).…”

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confidence: 76%

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The pathological significance of abnormal RON and PD-L1 expression in colorectal cancer

Liu¹,

Han²,

Shi³

et al. 2020

Preprint

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Background: PD-L1 immunotherapy remains poorly efficacious in colorectal cancer. The RON receptor tyrosine kinase plays an important role in regulating tumor immunity. Here, we identify patterns of RON and PD-L1 expression and explore the clinical significance of these patterns in colorectal cancer. Methods: Gene expression data were obtained from the Gene Expression Omnibus database (GEO; n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZUSM; n = 381) and were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor cells and the tumor microenvironment of colorectal cancer. Human colorectal cancer cell lines were treated with BMS-777607 to explore the relationship between RON activity and PD-L1 protein expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and western blot. Results: In the GEO cohort, cut-off values for RON and PD-L1 expression of 7.70 and 4.30, respectively, were determined. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 associated with poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and in tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121 (32%), 43 (11%), 91 (24%), and 51 (13.4%), respectively. High expression of RON and high expression of PD-L1 in the tumor cell compartment was significantly correlated (p < 0.001). High expression of RON and PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with poor prognosis. In vitro , BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in colorectal cancer cells. Conclusions: RON, PD-L1 and the crosstalk between these proteins plays an important role in predicting the prognostic value of colorectal cancer. Moreover, phosphorylation of RON upregulates the expression of PD-L1, which provides a novel approach to immunotherapy in colorectal cancer.

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confidence: 76%

“…Our results and previous studies demonstrate that high expression of RON or PD-L1 in CRC tumor tissues correlates with the extent of primary tumor, lymph node metastasis, and distant metastasis(39,40). Furthermore, high expression of RON or PD-L1 in the tumor microenvironment was associated with poor survival in CRC patients(22,(39)(40)(41)(42).…”

supporting

confidence: 76%

The pathological significance of abnormal RON and PD-L1 expression in colorectal cancer

Liu¹,

Han²,

Shi³

et al. 2020

Preprint

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“…When PD-1 binds to its ligand PD-L1, it serves to down-regulate T-cell activity, thus playing an important role in harnessing autoimmune reactions in the normal body [61]. PD-L1 is expressed in a variety of solid tumors, including breast cancer, colorectal cancer, melanoma and lung cancer [62][63][64][65].…”

Section: Pd-1 and Pd-l1mentioning

confidence: 99%

Triple negative breast cancer – prognostic role of immune-related factors: a systematic review

et al. 2017

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Immune-related factors have the potential as both prognostic and predictive biomarkers for new treatments targeting the immune system in breast cancer. However, multivariate analyses, taking other well-known factors into account, are required to determine the true value of these biomarkers. Also, differences between TNBC and other types of breast cancer may have implications for treatment and use of immune-related factors as biomarkers.

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“…However, the prognostic role of PD-L1 expression in CRC is less clear, with some studies reporting conflicting results as to whether PD-L1 expression indicates a better or worse prognosis. The prognostic evaluation in these studies has been limited because they included patients at various disease stages and different study populations ( 23 – 27 ). The aim of this study was to evaluate the correlation between PD-L1 expression and long-term oncologic outcomes in CRC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic impact of programmed cell death ligand 1 expression on long‑term oncologic outcomes in colorectal cancer

et al. 2018

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The present study evaluated the association between programmed cell death ligand-1 (PD-L1) expression and long-term oncologic outcomes in colorectal cancer (CRC). PD-L1 expression was evaluated using immunohistochemistry in 175 patients who underwent surgical resection for CRC between September 1999 and August 2004. Patients were grouped according to PD-L1 expression, with 82 (46.9%) and 93 (53.1%) in the low and high PD-L1 expression groups, respectively. The overall survival (OS) and disease-free survival (DFS) rates were significantly better in the high expression group compared with in the low expression group (OS: 48.2 vs. 32.9%, P=0.047; DFS: 43.3 vs. 32.9%, P=0.021). According to the Tumor-Node-Metastasis stage subgroups, the OS rates in the low and high expression groups, respectively, were 66.7 and 60.0% in stage I (P=0.715), 51.8 and 46.7% in stage II (P=0.789), 19.6 and 51.1% in stage III (P=0.011) and 9.1 and 0% in stage IV (P=0.005). The DFS rates in the low and high expression groups, respectively, were 66.7 and 60.0% in stage I (P=0.715), 51.8 and 46.7% in stage II (P=0.857), 19.6 and 38.3% in stage III (P=0.006) and 9.1 and 0% in stage IV (P=0.700). The systemic recurrence rate was significantly higher in the low expression group compared with in the high expression group (42.7 vs. 12.9%, respectively, P=0.030). Low PD-L1 expression was significantly associated with tumor relapse and poor prognosis in stage III CRC.

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Prognostic value of programmed death‐ligand 1 expression in patients with stage III colorectal cancer

Cited by 53 publications

References 41 publications

The pathological significance of abnormal RON and PD-L1 expression in colorectal cancer

The pathological significance of abnormal RON and PD-L1 expression in colorectal cancer

Triple negative breast cancer – prognostic role of immune-related factors: a systematic review

Prognostic impact of programmed cell death ligand 1 expression on long‑term oncologic outcomes in colorectal cancer

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