Journal of Personalized Medicine

Editorial

Jump to: Research, Review

6 pages, 214 KiB

Open AccessEditorial

Special Issue: “Gastrointestinal Cancers and Personalized Medicine”

by Stefania Nobili and Enrico Mini

J. Pers. Med. 2022, 12(3), 338; https://doi.org/10.3390/jpm12030338 - 24 Feb 2022

Viewed by 1938

Abstract

Gastrointestinal cancers represent more than 25% of all diagnosed cancers and more than 36% of cancer-related deaths worldwide [...] Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

Research

Jump to: Editorial, Review

12 pages, 2590 KiB

Open AccessArticle

LAG-3 Expression Predicts Outcome in Stage II Colon Cancer

by Gaëlle Rhyner Agocs, Naziheh Assarzadegan, Richard Kirsch, Heather Dawson, José A. Galván, Alessandro Lugli, Inti Zlobec and Martin D. Berger

J. Pers. Med. 2021, 11(8), 749; https://doi.org/10.3390/jpm11080749 - 30 Jul 2021

Cited by 24 | Viewed by 3725

Abstract

Introduction: LAG-3 is an inhibitory immune checkpoint molecule that suppresses T cell activation and inflammatory cytokine secretion. T cell density in the tumor microenvironment of colon cancer plays an important role in the host’s immunosurveillance. We therefore hypothesized that LAG-3 expression on tumor-infiltrating [...] Read more.

Introduction: LAG-3 is an inhibitory immune checkpoint molecule that suppresses T cell activation and inflammatory cytokine secretion. T cell density in the tumor microenvironment of colon cancer plays an important role in the host’s immunosurveillance. We therefore hypothesized that LAG-3 expression on tumor-infiltrating lymphocytes (TILs) predicts outcome in patients with stage II colon cancer. Patients and Methods: Immunohistochemical staining for LAG-3 was performed on tissue microarrays (TMAs) of formalin-fixed paraffin-embedded tissue from 142 stage II colon cancer patients. LAG-3 expression was assessed in TILs within both the tumor front and tumor center and scored as either positive or negative. The primary endpoint was disease-free survival (DFS). Results: In patients diagnosed with stage II colon cancer, the presence of LAG-3 expression on TILs was significantly associated with better 5-year DFS (HR 0.34, 95% CI 0.14–0.80, p = 0.009). The effect on DFS was mainly due to LAG-3-positive TILs in the tumor front (HR 0.33, 95% CI 0.13–0.82, p = 0.012). Conclusion: Assessment of LAG-3 might help to predict outcomes in patients with stage II colon cancer and potentially identify those patients who might benefit from adjuvant chemotherapy. Therefore, LAG-3 may serve as a prognostic biomarker in stage II colon cancer. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

► Show Figures

Figure 1

22 pages, 4925 KiB

Open AccessFeature PaperArticle

Increased Expression of VANGL1 is Predictive of Lymph Node Metastasis in Colorectal Cancer: Results from a 20-Gene Expression Signature

by Noshad Peyravian, Stefania Nobili, Zahra Pezeshkian, Meysam Olfatifar, Afshin Moradi, Kaveh Baghaei, Fakhrosadat Anaraki, Kimia Nazari, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali, Enrico Mini and Ehsan Nazemalhosseini Mojarad

J. Pers. Med. 2021, 11(2), 126; https://doi.org/10.3390/jpm11020126 - 14 Feb 2021

Cited by 5 | Viewed by 3168

Abstract

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate [...] Read more.

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I–IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

► Show Figures

Graphical abstract

19 pages, 4410 KiB

Open AccessArticle

Thermal Liquid Biopsy (TLB) Focused on Benign and Premalignant Pancreatic Cyst Diagnosis

by Sonia Hermoso-Durán, Guillermo García-Rayado, Laura Ceballos-Laita, Carlos Sostres, Sonia Vega, Judith Millastre, Oscar Sánchez-Gracia, Jorge L. Ojeda, Ángel Lanas, Adrián Velázquez-Campoy and Olga Abian

J. Pers. Med. 2021, 11(1), 25; https://doi.org/10.3390/jpm11010025 - 31 Dec 2020

Cited by 8 | Viewed by 2632

Abstract

Background: Current efforts in the identification of new biomarkers are directed towards an accurate differentiation between benign and premalignant cysts. Thermal Liquid Biopsy (TLB) has been previously applied to inflammatory and tumor diseases and could offer an interesting point of view in this [...] Read more.

Background: Current efforts in the identification of new biomarkers are directed towards an accurate differentiation between benign and premalignant cysts. Thermal Liquid Biopsy (TLB) has been previously applied to inflammatory and tumor diseases and could offer an interesting point of view in this type of pathology. Methods: In this work, twenty patients (12 males and 8 females, average ages 62) diagnosed with a pancreatic cyst benign (10) and premalignant (10) cyst lesions were recruited, and biological samples were obtained during the endoscopic ultrasonography procedure. Results: Proteomic content of cyst liquid samples was studied and several common proteins in the different groups were identified. TLB cyst liquid profiles reflected protein content. Also, TLB serum score was able to discriminate between healthy and cysts patients (71% sensitivity and 98% specificity) and between benign and premalignant cysts (75% sensitivity and 67% specificity). Conclusions: TLB analysis of plasmatic serum sample, a quick, simple and non-invasive technique that can be easily implemented, reports valuable information on the observed pancreatic lesion. These preliminary results set the basis for a larger study to refine TLB serum score and move closer to the clinical application of TLB providing useful information to the gastroenterologist during patient diagnosis. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

► Show Figures

Graphical abstract

19 pages, 1961 KiB

Open AccessArticle

Precision Medicine for the Management of Therapy Refractory Colorectal Cancer

by Hossein Taghizadeh, Robert M. Mader, Leonhard Müllauer, Friedrich Erhart, Alexandra Kautzky-Willer and Gerald W. Prager

J. Pers. Med. 2020, 10(4), 272; https://doi.org/10.3390/jpm10040272 - 11 Dec 2020

Cited by 5 | Viewed by 2779

Abstract

In this analysis, we examined the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated metastatic colorectal cancer (mCRC) patients after failure of all standard treatments. In this single-center, real-world retrospective analysis of our platform for precision medicine, we mapped the [...] Read more.

In this analysis, we examined the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated metastatic colorectal cancer (mCRC) patients after failure of all standard treatments. In this single-center, real-world retrospective analysis of our platform for precision medicine, we mapped the molecular profiles of 60 mCRC patients. Tumor samples of the patients were analyzed using next-generation sequencing panels of mutation hotspots, microsatellite instability testing, and immunohistochemistry. All profiles were reviewed by a multidisciplinary team to provide a targeted treatment recommendation after consensus discussion. In total, we detected 166 mutations in 53 patients. The five most frequently found mutations were TP53, KRAS, APC, PIK3CA, and PTEN. In 28 cases (47% of all patients), a molecularly targeted therapy could be recommended. Eventually, 12 patients (20%) received the recommended therapy. Six patients (10%) had a clinical benefit. The median time to treatment failure was 3.1 months. Our study demonstrates the feasibility and applicability of using targeted therapies in daily clinical practice for heavily pretreated mCRC patients. This could be used as a targeted treatment option in half of the patients. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

► Show Figures

Figure 1

10 pages, 1048 KiB

Open AccessArticle

Prognostic Impact of the Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratio, in Patients with Rectal Cancer: A Retrospective Study of 1052 Patients

by Zsolt Zoltán Fülöp, Réka Linda Fülöp, Simona Gurzu, Tivadar Bara, Jr., József Tímár, Emőke Drágus and Ioan Jung

J. Pers. Med. 2020, 10(4), 173; https://doi.org/10.3390/jpm10040173 - 16 Oct 2020

Cited by 17 | Viewed by 2383

Abstract

Despite the description of several new prognostic markers, colorectal cancer still represents the third most frequent cause of cancer-related death. As immunotherapy is considered a therapeutic alternative in such patients, neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratio (LMR) are hypothesized to provide reliable prognostic information. [...] Read more.

Despite the description of several new prognostic markers, colorectal cancer still represents the third most frequent cause of cancer-related death. As immunotherapy is considered a therapeutic alternative in such patients, neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratio (LMR) are hypothesized to provide reliable prognostic information. A retrospective study was conducted on 1052 patients operated on during 2013–2019 in two clinical hospitals from Hungary and Romania. Inclusion criteria targeted patients over 18 years old, diagnosed with rectal cancer, with preoperatively defined NLR and LMR. The overall survival rate, along with clinical and histopathological data, was evaluated. Overall survival was significantly associated with increased NLR (p = 0.03) and decreased LMR (p = 0.04), with cut-off values of 3.11 and 3.39, respectively. The two parameters were inversely correlated (p < 0.0001). There was no statistically significant association between tumor stage and NLR or LMR (p = 0.30, p = 0.06, respectively). The total mesorectal excision was especially obtained in cases with low NLR (p = 0.0005) and high LMR (p = 0.0009) values. A significant association was also seen between preoperative chemoradiotherapy and high NLR (p = 0.0001) and low LMR (p = 0.0001). In patients with rectal cancer, the preoperative values of NLR and LMR can be used as independent prognostic parameters. An NLR value of ≥3.11 can be used to indicate the response to preoperative chemoradiotherapy, but a low chance of sphincter preservation or obtaining a complete TME. Higher values of NLR and lower values of LMR require a more attentive preoperative evaluation of the mesorectum. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

13 pages, 3660 KiB

Open AccessReview

Defects in MMR Genes as a Seminal Example of Personalized Medicine: From Diagnosis to Therapy

by Arianna Dal Buono, Federica Gaiani, Laura Poliani, Carmen Correale and Luigi Laghi

J. Pers. Med. 2021, 11(12), 1333; https://doi.org/10.3390/jpm11121333 - 8 Dec 2021

Cited by 13 | Viewed by 3150

Abstract

Microsatellite instability (MSI) is the landmark feature of DNA mismatch repair deficiency, which can be found in 15–20% of all colorectal cancers (CRC). This specific set of tumors has been initially perceived as a niche for geneticists or gastroenterologists focused on inherited predispositions. [...] Read more.

Microsatellite instability (MSI) is the landmark feature of DNA mismatch repair deficiency, which can be found in 15–20% of all colorectal cancers (CRC). This specific set of tumors has been initially perceived as a niche for geneticists or gastroenterologists focused on inherited predispositions. However, over the years, MSI has established itself as a key biomarker for the diagnosis, then extending to forecasting the disease behavior and prognostication, including the prediction of responsiveness to immunotherapy and eventually to kinase inhibitors, and possibly even to specific biological drugs. Thanks to the contribution of the characterization of MSI tumors, researchers have first acknowledged that a strong lymphocytic reaction is associated with a good prognosis. This understanding supported the prognostic implications in terms of the low metastatic potential of MSI-CRC and has led to modifications in the indications for adjuvant treatment. Furthermore, with the emergence of immunotherapy, this strong biomarker of responsiveness has exemplified the capability of re-activating an effective immune control by removing the brakes of immune evasion. Lately, a subset of MSI-CRC emerged as the ideal target for kinase inhibitors. This therapeutic scenario implies a paradox in which appropriate treatments for advanced disease are effective in a set of tumors that seldom evolve towards metastases. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

► Show Figures

Figure 1

21 pages, 1325 KiB

Open AccessReview

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

by Roser Velasco, Montserrat Alemany, Macarena Villagrán and Andreas A. Argyriou

J. Pers. Med. 2021, 11(7), 669; https://doi.org/10.3390/jpm11070669 - 16 Jul 2021

Cited by 11 | Viewed by 4009

Abstract

Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent [...] Read more.

Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent sensory neuronopathy symmetrically affecting both upper and lower limbs in a stocking-and-glove distribution. No effective strategy has been established to reverse or treat OXAIPN. Thus, it is necessary to early predict the occurrence of OXAIPN during treatment and possibly modify the OXA-based regimen in patients at high risk as an early diagnosis and intervention may slow down neuropathy progression. However, identifying which patients are more likely to develop OXAIPN is clinically challenging. Several objective and measurable early biomarkers for OXAIPN prediction have been described in recent years, becoming useful for informing clinical decisions about treatment. The purpose of this review is to critically review data on currently available or promising predictors of OXAIPN. Neurological monitoring, according to predictive factors for increased risk of OXAIPN, would allow clinicians to personalize treatment, by monitoring at-risk patients more closely and guide clinicians towards better counseling of patients about neurotoxicity effects of OXA. Full article

(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Gastrointestinal Cancers and Personalized Medicine

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI