PSMB8 as a Candidate Marker of Responsiveness to Preoperative Radiation Therapy in Rectal Cancer Patients

Ha, Ye Jin; Tak, Ka Hee; Kim, Chan Wook; Roh, Seon Ae; Choi, Eun Kyung; Cho, Dong Hyung; Kim, Jeong Hwan; Kim, Seon‐Kyu; Kim, Yong‐Sung; Kim, Jin Cheon

doi:10.1016/j.ijrobp.2017.03.023

Cited by 28 publications

(29 citation statements)

References 24 publications

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“…PSMB8 was reported to be a target gene of miR‐451a in A549 lung cancer cells . Strong expression of PSMB8 was also reported to be correlated with increased depth of local invasion and lymph node metastasis in gastric cancer . Based on these reported results and our own results, we suggested that miR‐451a may act as a cancer suppressor by inhibiting the cancer promoter function of PSMB8 in PTC.…”

Section: Discussionsupporting

confidence: 65%

“…27 Strong expression of PSMB8 was also reported to be correlated with increased depth of local invasion and lymph node metastasis in gastric cancer. 28 Based on these reported results and our own results, we suggested that miR-451a may act as a cancer suppressor by inhibiting the cancer promoter function of PSMB8 in PTC. This miR-451a/PSMB8 axis may serve as novel therapy targets for PTC patients.…”

Section: Discussionmentioning

confidence: 52%

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miR‐451a inhibits cancer growth, epithelial‐mesenchymal transition and induces apoptosis in papillary thyroid cancer by targeting PSMB8

Fan

Zhao

2019

J Cellular Molecular Medi

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Despite the increasing incidence of papillary thyroid cancer in the past decade, the molecular mechanism underlying its progression remains unknown. Several studies have reported down‐regulation of miR‐451a or circular miR‐451a in papillary thyroid cancer cell lines or patients. However, the underlying molecular mechanism remains unknown. In this study, we found that overexpression of miR‐451a could inhibit proliferation, epithelial‐mesenchymal transition and induce apoptosis in papillary thyroid cancer cells. Proteasome subunit beta type‐8 was predicted to be a direct target of miR‐451a and was validated with a luciferase reporter assay. Further functional assays showed that miR‐451a could inhibit thyroid cancer progression by targeting proteasome subunit beta type‐8.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 52%

miR‐451a inhibits cancer growth, epithelial‐mesenchymal transition and induces apoptosis in papillary thyroid cancer by targeting PSMB8

Fan

Zhao

2019

J Cellular Molecular Medi

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“…28 Inhibition of PSMB8 may deplete T cell mediated anti-tumor immunity in vitro, 28 and PSMB8 is also reported as a predictor of radiation sensitivity in rectal cancer. 29 It is therefore biologically plausible that rs16871026 may affect PCa aggressiveness and reclassification through altered function of PSMB8, though further study is still warranted.…”

Section: Discussionmentioning

confidence: 99%

Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort

Wang

Gregg

et al. 2018

OncoImmunology

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Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D'Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of PSMB8 was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D'Amico high risk disease (P-trend = 2.4E-09), GS4 + 3 disease (P-trend = 1.3E-04), biochemical recurrence (P-trend = 0.01) and reclassification (P-trend = 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes.

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“…Approximately 15% to 45% of LARC patients develop resistance to NCRT. 31 Unfortunately, there is a lack of reliable biomarkers and the mechanisms of resistance to NCRT are still unclear. Previous studies have demonstrated that FOXK2 expression is associated with the response to paclitaxel in breast cancer, 32 and Wu et al reported that knockdown of FOXK1 promoted 5-fluorouracil (FU)-induced apoptosis in colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy</p>

Zhang

Chen

et al. 2020

OTT

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Purpose To assess the role of the expression levels of FOXK family members, FOXK1 and FOXK2, in predicting response to neo-chemoradiotherapy (NCRT) and prognosis in locally advanced rectal cancer (LARC). Methods A total of 256 LARC patients who underwent NCRT and radical resection between 2011 and 2017 were enrolled in the present study. The patients were divided into a training dataset (n=169, 2011–2015) and a validation dataset (n=87, 2016–2017). Tumor tissues were collected before NCRT and post-surgery and were used for immunohistochemical analysis. Results Oncomine database analysis revealed that FOXK1 and FOXK2 were overexpressed in most cancers especially in colorectal cancer. Additionally, overexpression of FOXK1 and FOXK2 was associated with poorer prognosis by the R2 database. In both our training and validation datasets, the expression of FOXK1 and FOXK2 was lower in the pathological complete response (pCR) group compared with the non-pCR group (P<0.05). Cox regression analysis demonstrated that pathological N stage (HR=1.810, 95% CI 1.159–2.827, P=0.009), FOXK1 expression (HR=5.831, 95% CI 2.925–11.625, P<0.001), and FOXK2 expression (HR=2.390, 95% CI 11.272–4.491, P=0.007) were independent predictors of disease-free survival (DFS). Based on the Cox multivariate analysis, we constructed a risk score model that served as a prognostic biomarker and had a powerful ability to predict pCR in LARC patients upon NCRT in both training and validation groups. Conclusion Expression levels of FOXK family members were associated with chemoradiotherapy resistance and prognosis of LARC patients following NCRT and were used to construct a risk score model that is a promising biomarker for LARC.

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PSMB8 as a Candidate Marker of Responsiveness to Preoperative Radiation Therapy in Rectal Cancer Patients

Cited by 28 publications

References 24 publications

miR‐451a inhibits cancer growth, epithelial‐mesenchymal transition and induces apoptosis in papillary thyroid cancer by targeting PSMB8

miR‐451a inhibits cancer growth, epithelial‐mesenchymal transition and induces apoptosis in papillary thyroid cancer by targeting PSMB8

Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort

<p>Prognostic Value of the FOXK Family Expression in Patients with Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy</p>

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