Molecular and Kinetic Analyses of Circulating Tumor Cells as Predictive Markers of Treatment Response in Locally Advanced Rectal Cancer Patients

Flores, Bianca C. T.; Silva, Virgílio Souza e; Abdallah, Emne Ali; Mello, Celso Abdon Lopes de; Silva, Maria Letícia Gobo; Mendes, Gustavo Gomes; Braun, Alexcia Camila; Aguiar, Samuel; Chinen, Ludmilla Thomé Domingos

doi:10.3390/cells8070641

Cited by 38 publications

(23 citation statements)

References 48 publications

(54 reference statements)

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“…TYMS is a rate-limiting enzyme, which plays an important role in regulating the pyrimidine metabolism signaling pathway ( Yeh et al, 2017 ). TYMS is overexpressed frequently in different kinds of cancers, such as NSCLC, pancreatic, colorectal, and breast cancers, and it has resulted in a poor cancer prognosis and chemotherapy resistance via dysregulating pyrimidine metabolism ( TroncarelliFlores et al, 2019 ; Wu et al, 2019 ). In our study, we constructed a six-gene signature for a prognostic model based on the TCGA database.…”

Section: Discussionmentioning

confidence: 99%

Identification of a six-gene metabolic signature predicting overall survival for patients with lung adenocarcinoma

Cao

Lü

et al. 2020

PeerJ

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Background Lung cancer is the leading cause of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) is one of the main subtypes of lung cancer. Hundreds of metabolic genes are altered consistently in LUAD; however, their prognostic role remains to be explored. This study aimed to establish a molecular signature that can predict the prognosis in patients with LUAD based on metabolic gene expression. Methods The transcriptome expression profiles and corresponding clinical information of LUAD were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) between LUAD and paired non-tumor samples were identified by the Wilcoxon rank sum test. Univariate Cox regression analysis and the lasso Cox regression model were used to construct the best-prognosis molecular signature. A nomogram was established comprising the prognostic model for predicting overall survival. To validate the prognostic ability of the molecular signature and the nomogram, the Kaplan–Meier survival analysis, Cox proportional hazards model, and receiver operating characteristic analysis were used. Results The six-gene molecular signature (PFKP, PKM, TPI1, LDHA, PTGES, and TYMS) from the DEGs was constructed to predict the prognosis. The molecular signature demonstrated a robust independent prognostic ability in the training and validation sets. The nomogram including the prognostic model had a greater predictive accuracy than previous systems. Furthermore, a gene set enrichment analysis revealed several significantly enriched metabolic pathways, which suggests a correlation of the molecular signature with metabolic systems and may help explain the underlying mechanisms. Conclusions Our study identified a novel six-gene metabolic signature for LUAD prognosis prediction. The molecular signature could reflect the dysregulated metabolic microenvironment, provide potential biomarkers for predicting prognosis, and indicate potential novel metabolic molecular-targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Identification of a six-gene metabolic signature predicting overall survival for patients with lung adenocarcinoma

Cao

Lü

et al. 2020

PeerJ

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“…Recently, the role of CTCs in LARC patients undergoing nCRT followed by surgery has been explored by evaluating the predictive values of the enzyme thymidylate synthase (TYMS), the main target of 5-FU and the ultraviolet excision repair protein, RAD23 homolog B (RAD23B) before and after nCRT [ 114 ]. This study revealed that TYMS mRNA and/or TYMS/RAD23B protein expression in CTCs have the potential to predict non-response to nCRT and avoid unnecessary radical surgery for LARC patients with pCR [ 114 ].…”

Section: Circulating Biomarkers To Predict Response To Ncrt In Larmentioning

confidence: 99%

The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Palma

Luglio

Tropeano

et al. 2020

IJMS

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The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.

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“…It enabled them to detect in isolated CTCs two molecules increasing chemotherapy and radiotherapy resistance: thymidylate synthase (TYMS) and excision repair protein RAD23 homolog B (RAD23B). Interestingly, CTCs in all patients with pCR after CRT had undetectable expression of both TYMS and RAD23B [58].…”

Section: Circulating Biomarkers In Rectal Cancermentioning

confidence: 99%

Translational Potential of MicroRNAs for Preoperative Staging and Prediction of Chemoradiotherapy Response in Rectal Cancer

Macháčková

Procházka

Kala

et al. 2019

Cancers

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Colorectal cancer is the third most common cancer and the second cause of cancer-related deaths. Rectal cancer presents roughly one-third of all colorectal cancer cases and differs from it on both anatomical and molecular levels. While standard treatment of colon cancer patients is radical surgery, rectal cancer is usually treated with pre-operative chemoradiotherapy followed by total mesorectal excision, which requires precise estimation of TNM staging. Unfortunately, stage evaluation is based solely on imaging modalities, and they often do not correlate with postoperative pathological findings. Moreover, approximately half of rectal cancer patients do not respond to such pre-operative therapy, so they are exposed to its toxic effects without any clinical benefit. Thus, biomarkers that could precisely predict pre-operative TNM staging, and especially response to therapy, would significantly advance rectal cancer treatment—but till now, no such biomarker has been identified. In cancer research, microRNAs are emerging biomarkers due to their connection with carcinogenesis and exceptional stability. Circulating miRNAs are promising non-invasive biomarkers that could allow monitoring of a patient throughout the whole therapeutic process. This mini-review aims to summarize the current knowledge on miRNAs and circulating miRNAs involved in the prediction of response to treatment and pre-operative staging in rectal cancer patients.

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Molecular and Kinetic Analyses of Circulating Tumor Cells as Predictive Markers of Treatment Response in Locally Advanced Rectal Cancer Patients

Cited by 38 publications

References 48 publications

Identification of a six-gene metabolic signature predicting overall survival for patients with lung adenocarcinoma

Identification of a six-gene metabolic signature predicting overall survival for patients with lung adenocarcinoma

The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Translational Potential of MicroRNAs for Preoperative Staging and Prediction of Chemoradiotherapy Response in Rectal Cancer

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