Identification of Serum Biomarkers of Chemoradiosensitivity in Esophageal Cancer Via the Targeted Metabolomics Approach

Fujigaki, Seiji; Nishiumi, Shin; Kobayashi, Takashi; Suzuki, Makoto; Iemoto, Takao; Kojima, Takashi; Ito, Yoshiaki; Daiko, Hiroyuki; Kato, Ken; Shouji, Hirokazu; Honda, Kazufumi; Azuma, Takeshi; Yoshida, Masaru

doi:10.2217/bmm-2017-0449

Cited by 16 publications

(15 citation statements)

References 56 publications

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“…In the previous study, altered metabolic profile was found between the pCR and non-pCR ESCC patients in the serum level detected by gas chromatography mass spectrometry (GC/MS) analysis and liquid chromatography mass spectrometry (LC/MS) analysis [21]. But only three differential metabolites (arabitol, uracil and 3-aminoglutaric acid) were detected by GC/ MS analysis.…”

Section: Discussionmentioning

confidence: 92%

“…In addition, multiple metabolites have been found to be strongly associated with the degree of tumor progression through metabolomics-based methods [ 19 , 20 ]. As for the biomarker screening for chemoradiosensitivity in ESCC, one research with small sample size revealed that serum levels of several metabolites differed significantly between the pathological complete response (pCR) group and non-pCR group [ 21 ]. However, no other external validation was provided.…”

Section: Introductionmentioning

confidence: 99%

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Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach

et al. 2020

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Background: To investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC). Methods: A total of 46 ESCC patients were included in this study. Gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was applied to detect the plasma samples collected before nCRT via untargeted metabolomics analysis. Results: Five differentially expressed metabolites (out of 109) was found in plasma between pCR and non-pCR groups. Compared with non-pCR group, isocitric acid (p = 0.0129), linoleic acid (p = 0.0137), citric acid (p = 0.0473) were upregulated, while L-histidine (p = 0.0155), 3′4 dihydroxyhydrocinnamic acid (p = 0.0339) were downregulated in the pCR plasma samples. Pathway analyses unveiled that citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolic pathway were associated with ESCC chemoradiosensitivity. Conclusion: The present study provided supporting evidence that GC-TOF/MS based metabolomics approach allowed identification of metabolite differences between pCR and non-pCR patients in plasma levels, and the systemic metabolic status of patients may reflect the response of ESCC patient to neoadjuvant chemoradiotherapy.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach

et al. 2020

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“…The GC/MS extraction and derivatization procedures were performed according to the methods described in our previous studies (20–22,27). A total of 20 µl of each sample was dispensed into a 1.5-ml Eppendorf tube.…”

Section: Methodsmentioning

confidence: 99%

“…The GC/MS analysis was performed on a GCMS-TQ8040 GC-MS/MS system (Shimadzu Corporation, Kyoto, Japan) with a fused silica capillary column (BPX5; inner diameter: 30 m × 0.25 mm; film thickness, 0.25 µm; SGE Analytical Science, Melbourne, Australia). The data processing was performed according to previously described methods (21,22,27). The MS data were exported to a personal computer, on which the GCMS solution software ver.…”

Section: Methodsmentioning

confidence: 99%

“…According to the method described in our previous studies (20,27), the LC/MS analysis was performed using a Nexera LC system (Shimadzu Corporation) equipped with two LC-30AD autosamplers, a CTO-20AC column oven and a CBM-20A control module, coupled with an LCMS-8040 triple quadruple mass spectrometer (Shimadzu Corporation). The analytical conditions of LC/MS were as follows: Electrospray voltage: 3.5 kV, −3.5 kV; Curve desolvation line (CDL): 250°C; Heat block temperature: 400°C; Nebulizing gas (N 2 ): 3.0 l/min; Drying gas pressure: 15 l/min; CID gas (Argon) pressure: 0.23 MPa.…”

Section: Methodsmentioning

confidence: 99%

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Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer

et al. 2018

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The survival times of patients with advanced colorectal cancer (CRC) have increased due to the introduction of chemotherapy involving irinotecan and cetuximab. However, further studies are required on the effective pretreatment methods for identifying patients with CRC who would respond to particular treatments. The aim of the present study was to identify biomarkers for predicting the efficacy of chemotherapy for CRC. A total of 123 serum samples were collected from 31 patients with CRC just prior to each of the first four rounds of chemotherapy. Serum metabolome analysis was performed using a multiplatform metabolomics system, and univariate Cox regression hazards analysis of the time to disease progression was conducted. Octanoic acid and 1,5-anhydro-D-glucitol were identified as biomarker candidates. In addition, the serum level of octanoic acid was indicated to be significantly associated with the time to disease progression (hazard ratio, 3.3; 95% confidence interval, 1.099–11.840; P=0.033). The serum levels of fatty acids, in particular polyunsaturated fatty acids, tended to be downregulated in the partial response group. The findings of the present study suggest that the serum level of octanoic acid may serve as a useful predictor for the prognosis of CRC.

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Nomogram for predicting pathologic complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma

Liu,

Chen,

Zhang

et al. 2024

Cancer Medicine

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PurposeA pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in up to 40% of the patients with esophageal squamous cell carcinoma (ESCC). No nomogram has been constructed for the prediction of pCR for patients whose primary chemotherapy was a taxane‐based regimen. The aim is to identify characteristics associated with a pCR through analyzing multiple pre‐ and post‐nCRT variables and to develop a nomogram for the prediction of pCR for these patients by integrating clinicopathological characteristics and hematological biomarkers.Materials and MethodsWe analyzed 293 patients with ESCC who underwent nCRT followed by esophagectomy. Clinicopathological factors, hematological parameters before nCRT, and hematotoxicity during nCRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and evaluated for both discrimination and calibration.ResultsAfter surgery, 37.88% of the study patients achieved pCR. Six variables were included in the nomogram: sex, cN stage, chemotherapy regimen, duration of nCRT, pre‐nCRT neutrophil‐to‐lymphocyte ratio (NLR), and pre‐nCRT platelet‐to‐lymphocyte ratio (PLR). The nomogram indicated good accuracy and consistency in predicting pCR, with a C‐index of 0.743 (95% confidence interval: 0.686, 0.800) and a p value of 0.600 (>0.05) in the Hosmer–Lemeshow goodness‐of‐fit test.ConclusionsFemale, earlier cN stage, duration of nCRT (< 62 days), chemotherapy regimen of taxane plus platinum, pre‐nCRT NLR (≥2.199), and pre‐nCRT PLR (≥99.302) were significantly associated with a higher pCR in ESCC patients whose primary chemotherapy was a taxane‐based regimen for nCRT. A nomogram was developed and internally validated, showing good accuracy and consistency.

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Identification of Serum Biomarkers of Chemoradiosensitivity in Esophageal Cancer Via the Targeted Metabolomics Approach

Abstract: The serum levels of metabolites might be useful for predicting the chemoradiosensitivity of ESCC patients.

Cited by 16 publications

References 56 publications

Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach

Alteration of plasma metabolites associated with chemoradiosensitivity in esophageal squamous cell carcinoma via untargeted metabolomics approach

Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer

Nomogram for predicting pathologic complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma

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