Clinical application of the biomarkers for the selection of adjuvant chemotherapy in pancreatic ductal adenocarcinoma

Oba, Atsushi; Ban, Daisuke; Kirimura, Susumu; Akahoshi, Keiichi; Mitsunori, Yusuke; Matsumura, Satoshi; Ochiai, Takanori; Kudo, Akira; Tanaka, Shinji; Tanabe, Minoru

doi:10.1002/jhbp.366

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…HuR expression levels also influenced chemotherapy resistance. Pancreatic cancer patients with high HuR protein expressing tumors, treated with gemcitabine, showed a significantly longer DFS rate than those with low HuR expression [44]. On the other hand,…”

Section: Clinical Significance Of Hur Expressionmentioning

confidence: 94%

HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment

et al. 2021

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Hu-antigen R (HuR) is a post-transcriptional regulator that belongs to the embryonic lethal abnormal vision Drosophila-like family (ELAV). HuR regulates the stability, translation, subcellular localization, and degradation of several target mRNAs, which are implicated in carcinogenesis and could affect therapeutic options. HuR protein is consistently highly expressed in hepatocellular carcinoma (HCC) compared to the adjacent normal liver tissue and is involved in the post-transcriptional regulation of various genes implicated in liver malignant transformation. Additionally, HuR protein seems to be a putative prognosticator in HCC, predicting worse survival. This review summarizes the recent evidence regarding the role of HuR in primary liver tumors, as presented in clinical studies, in vitro experiments and in vivo animal models. In conclusion, our review supports the consistent role of HuR protein in the development, prognosis, and treatment of HCC. Additional studies are expected to expand current information and exploit its putative employment as a future candidate for more personalized treatment in these tumors.

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Section: Clinical Significance Of Hur Expressionmentioning

confidence: 94%

HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment

et al. 2021

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“…However, the guidelines do not clearly indicate how to select the optimal chemotherapy regimen for PDAC patients suitably and individualizedly, and which population can benefit from S-1 is still unknown; proper evidence-based guidance is still lacking. Some studies proposed that the intratumoural expression levels of DPD and thymidylate synthase (TS) might be related to therapeutic outcomes in PDAC patients receiving S-1 chemotherapy [21][22][23], but the conclusion remains controversial; some studies even had contradictory results [24,25].…”

Section: Discussionmentioning

confidence: 99%

Whole-tumour evaluation with MRI and radiomics features to predict the efficacy of S-1 for adjuvant chemotherapy in postoperative pancreatic cancer patients: a pilot study

Liang

Ding

et al. 2021

BMC Med Imaging

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Background Multiple guidelines for pancreatic ductal adenocarcinoma (PDAC) suggest that all stages of patients need to receive postoperative adjuvant chemotherapy. S-1 is a recently emerged oral antitumour agent recommended by the guidelines. However, which population would benefit from S-1 needs to be determined, and predictors of chemotherapy response are needed for personalized precision medicine. This pilot study aimed to initially identify whether whole-tumour evaluation with MRI and radiomics features could be used for predicting the efficacy of S-1 and to find potential predictors of the efficacy of S-1 as evidence to assist personalized precision treatment. Methods Forty-six patients with PDAC (31 in the primary cohort and 15 in the validation cohort) who underwent curative resection and subsequently adjuvant chemotherapy with S-1 were included. Pre-operative abdominal contrast-enhanced MRI was performed, and radiomics features of the whole PDAC were extracted from the primary cohort. After univariable analysis and radiomics features selection, a multivariable Cox regression model for survival analysis was subsequently used to select statistically significant factors associated with postoperative disease-free survival (DFS). Predictive capacities of the factors were tested on the validation cohort by using Kaplan–Meier method. Results Multivariable Cox regression analysis identified the probability of T1WI_NGTDM_Strength and tumour location as independent predictors of the efficacy of S-1 for adjuvant chemotherapy of PDAC (p = 0.005 and 0.013) in the primary cohort, with hazard ratios (HRs) of 0.289 and 0.293, respectively. Further survival analysis showed that patients in the low-T1WI_NGTDM_Strength group had shorter DFS (median = 5.1 m) than those in the high-T1WI_NGTDM_Strength group (median = 13.0 m) (p = 0.006), and patients with PDAC on the pancreatic head exhibited shorter DFS (median = 7.0 m) than patients with tumours in other locations (median = 20.0 m) (p = 0.016). In the validation cohort, the difference in DFS between patients with low-T1WI_NGTDM_Strength and high-T1WI_NGTDM_Strength and the difference between patients with PDAC on the pancreatic head and that in other locations were approved, with marginally significant (p = 0.073 and 0.050), respectively. Conclusions Whole-tumour radiomics feature of T1WI_NGTDM_Strength and tumour location were potential predictors of the efficacy of S-1 and for the precision selection of S-1 as adjuvant chemotherapy regimen for PDAC.

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“…Oba et al studied 141 patients with PDAC who underwent surgery, and 61 of these patients received gemcitabine. The results showed that the disease-free survival (DFS) rate of patients treated with gemcitabine was significantly higher in patients with HuR overexpression than in those in the control group and that high HuR expression had a positive association with a good reaction to gemcitabine treatment [42]. In addition, Tatarian et al performed HuR immunolabeling in 379 PDA patients and divided the patients into a high-expression group and a low-expression group.…”

Section: Hur and Pancreaticmentioning

confidence: 99%

The RNA-Binding Protein HuR in Digestive System Tumors

Song

Shi²,

et al. 2020

BioMed Research International

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Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins. This molecule, which was first described in tumors nearly two decades ago, has recently received much attention in tumor-related research because it regulates the expression of many tumor-associated molecules through posttranscriptional regulatory mechanisms, thereby affecting biological characteristics. It is suggested that HuR might be a novel therapeutic target and a marker for therapeutic response and prognostic assessment. Increasing evidence supports that HuR also plays critical roles in the development, therapy, and prognosis of digestive system tumors. Herein, we review the relationships between HuR and digestive system tumors, demonstrating the importance of HuR in digestive system tumor diagnosis.

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Clinical application of the biomarkers for the selection of adjuvant chemotherapy in pancreatic ductal adenocarcinoma

Abstract: HuR and hENT1 were good candidates as selective biomarkers and this study's concept could contribute to personalized therapy for PDAC patients.

Cited by 7 publications

References 31 publications

HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment

HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment

Whole-tumour evaluation with MRI and radiomics features to predict the efficacy of S-1 for adjuvant chemotherapy in postoperative pancreatic cancer patients: a pilot study

The RNA-Binding Protein HuR in Digestive System Tumors

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