Novel Biomarkers in Gastrointestinal Malignancies

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Gastrointestinal Oncology".

Deadline for manuscript submissions: closed (10 June 2023) | Viewed by 6304

Special Issue Editors


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Guest Editor
Department of Oncology, Division of Oncology, University Hospital of Modena, Modena, Italy
Interests: colorectal cancer; gastric cancer; neuroendocrine tumors; hepatobiliary cancer; pancreatic cancer; precision medicine; clinical trials; translational research

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Guest Editor
Medical Oncology, Comprehensive Cancer Center, Azienda USL-IRCCS Reggio Emilia, 42122 Reggio Emilia, Italy
Interests: colorectal cancer; hepatobiliary cancer; gastric cancer; pancreatic cancer; clinical trials; translational research

Special Issue Information

Dear Colleagues,

There are a limited number of available treatments for most tumors of the gastrointestinal tract. Although multimodal treatment for locoregional disease has resulted in significant improvements, many patients still relapse and ultimately die. Patients are often diagnosed with metastatic disease, which generally portends a dismal prognosis; median survival in patients with advanced gastroesophageal and pancreatic cancer, for example, does not exceed one year with modern standard systemic treatments. Therefore, there is an urgent need for new biomarkers able to predict the efficacy of systemic treatments to prevent unnecessary toxicities and better allocate economic resources. However, despite the growing body of knowledge on the molecular aberrations underpinning these cancers, the biology of these tumors does not yet inform treatment choices in daily clinical practice. This Special Issue will highlight some translational aspects of research on the treatment of patients with gastrointestinal tumors, with a particular focus on novel biomarkers with promise in efficacious systemic treatments.

Dr. Fabio Gelsomino
Dr. Francesco Caputo
Guest Editors

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Keywords

  • predictive biomarkers
  • colorectal cancer
  • pancreatic cancer
  • hepatobiliary cancer
  • gastric cancer
  • neuroendocrine tumors

Published Papers (3 papers)

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Research

20 pages, 5062 KiB  
Article
CKLF as a Prognostic Biomarker and Its Association with Immune Infiltration in Hepatocellular Carcinoma
by Dan Li, Shenglan Huang, Chen Luo, Yongkang Xu, Shumin Fu, Kan Liu and Jianbing Wu
Curr. Oncol. 2023, 30(3), 2653-2672; https://doi.org/10.3390/curroncol30030202 - 22 Feb 2023
Cited by 2 | Viewed by 2027
Abstract
The Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of CMTM family members in hepatocellular carcinoma (HCC) are not [...] Read more.
The Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of CMTM family members in hepatocellular carcinoma (HCC) are not fully clarified. In this study, the RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas (TCGA) databases. The Kaplan–Meier method and the Cox proportional hazards regression analysis were used to evaluate the prognostic significance of CMTM family members. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were employed to explore the relationship between CMTM family genes and the tumor microenvironment in HCC. Finally, the prognostic CMTM family gene expression was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining in clinical HCC tissue specimens. The results indicated that, compared with normal tissues, the expression of CKLF, CMTM1, CMTM3, CMTM4, CMTM7, and CMTM8 were significantly upregulated in HCC, while the expression of CMTM2, CMTM5, and CMTM6 were significantly downregulated in HCC. Univariate and multivariate Cox regression analysis demonstrated that CKLF was an independent prognostic biomarker for the overall survival (OS) of HCC patients. In HCC, the expression of CKLF was found to be correlated with immune cell infiltration, immune-related functions, and immune checkpoint genes. The qRT-PCR and IHC confirmed that CKLF was highly expressed in HCC. Overall, this research suggested that CKLF is involved in immune cell infiltration and may serve as a critical prognostic biomarker, which provides new light on the therapeutics for HCC. Full article
(This article belongs to the Special Issue Novel Biomarkers in Gastrointestinal Malignancies)
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16 pages, 2085 KiB  
Article
Identification of Potential Predictors of Prognosis and Sorafenib-Associated Survival Benefits in Patients with Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization
by Kun He, Zelong Yang, Xinyu Liu, Yanling Yang, Wenjie Song, Shangyu Wang and Yong Chen
Curr. Oncol. 2023, 30(1), 476-491; https://doi.org/10.3390/curroncol30010038 - 29 Dec 2022
Cited by 1 | Viewed by 1860
Abstract
Some studies have shown that sorafenib could significantly prolong the overall survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization (TACE). However, other studies revealed that patients had no access to sorafenib-related survival benefits after TACE. To identify the predictive [...] Read more.
Some studies have shown that sorafenib could significantly prolong the overall survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization (TACE). However, other studies revealed that patients had no access to sorafenib-related survival benefits after TACE. To identify the predictive biomarkers of therapeutic efficacy of sorafenib, we explored the potential predictive value of vascular endothelial growth factor (VEGF) and other clinical variables for survival benefits from sorafenib in patients treated with TACE previously. The results demonstrated that patients with tumor size > 7 cm or total bilirubin ≤ 17.3 μmol/L showed significant survival benefits from sorafenib after TACE treatment compared with those with tumor size ≤ 7 cm or total bilirubin > 17.3 μmol/L. Meanwhile, patients with VEGF > 131.09 pg/mL may obtain sorafenib-associated survival benefits after TACE when compared to those with VEGF ≤ 131.09 pg/mL, which needs further confirmation. The abovementioned results are helpful to confirm the specific population who are sensitive to targeted therapy. (1) Background: VEGF plays a crucial role in modulating proliferation and metastasis in HCC. We aimed to explore the relationship between VEGF and the prognosis, as well as the mortality risk of HCC patients who received TACE, and whether it and other variables could be considered as potential biomarkers for predicting the benefits from sorafenib. (2) Method: A total of 230 consecutive newly diagnosed patients with unresectable HCC treated with either TACE or TACE–sorafenib were collected retrospectively. Cox regression analyses were performed to evaluate the prognostic value of VEGF. Furthermore, restricted cubic splines were fitted to assess the nonlinear associations between VEGF and OS, and the threshold effect analysis was subsequently performed. Lastly, the potential factors for predicting the survival benefits from sorafenib after the TACE procedure were identified using the Cox proportional hazard model with an interaction term. (3) Results: VEGF was recognized as an independent prognostic factor for OS in the TACE alone cohort (HR = 3.237, p = 0.013). A nonlinear relationship was observed between VEGF and OS in HCC patients with TACE administration after adjustment for confounders (p for nonlinearity = 0.030); the mortality risk increased with increasing the baseline VEGF before the inflection point, and the HR for death was 1.008. There was no significant interaction between the VEGF levels and treatment modality (p for interaction = 0.233), and further studies are needed to identify its predictive value on the efficacy of sorafenib. Patients with tumor size > 7 cm or total bilirubin ≤ 17.3 μmol/L derived significant sorafenib-related benefits in OS when compared to those with tumor size ≤ 7 cm or total bilirubin > 17.3 μmol/L (p for interaction = 0.004 and 0.031, respectively). (4) Conclusions: Within a certain concentration range, elevated baseline VEGF meant an increased risk of death in HCC patients treated with TACE. Significant improvements in OS associated with sorafenib were observed in patients with higher tumor size and lower total bilirubin after TACE treatment. Full article
(This article belongs to the Special Issue Novel Biomarkers in Gastrointestinal Malignancies)
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15 pages, 2197 KiB  
Article
Overexpression of AKR1B10 Predicts Poor Prognosis in Gastric Cancer Patients Undergoing Surgical Resection
by Yu-Yin Liu, Yueh-Wei Liu, Gong-Kai Huang, Kuo-Chen Hung, Yu-Hung Lin, Cheng-Hsi Yeh, Shih-Min Yin, Ching-Hua Tsai and Yen-Hao Chen
Curr. Oncol. 2023, 30(1), 85-99; https://doi.org/10.3390/curroncol30010007 - 21 Dec 2022
Cited by 2 | Viewed by 1689
Abstract
Aldo–keto reductase family 1 member B10 (AKR1B10) is associated with several cancers, but the prognostic role in gastric cancer (GC) remains unclear. We enrolled 359 GC patients who underwent a gastrectomy with D2 lymph node dissection. AKR1B10 expression was scored using an immunoreactive [...] Read more.
Aldo–keto reductase family 1 member B10 (AKR1B10) is associated with several cancers, but the prognostic role in gastric cancer (GC) remains unclear. We enrolled 359 GC patients who underwent a gastrectomy with D2 lymph node dissection. AKR1B10 expression was scored using an immunoreactive scoring system based on immunohistochemistry. Adjuvant chemotherapy with S-1 or oxaliplatin plus capecitabine was administered to pathological stage II or III disease patients. There were 117 (32.6%) and 242 (67.4%) patients with AKR1B10 overexpression and low expression, respectively. Patients overexpressing AKR1B10 had worse 5-year disease-free survival (DFS) and overall survival (OS) rates than those with low expression of AKR1B10. Pathological T3–T4 stage, pathological stage III, lymph node ratio ≥25%, and AKR1B10 overexpression were independent prognostic factors for worse DFS and OS in univariate and multivariate analyses. For 162 stage II or III patients who received adjuvant chemotherapy after surgical resection and 59 patients with signet ring cell carcinoma histology, AKR1B10 overexpression was also associated with inferior DFS and OS. AKR1B10 was not associated with clinical survival in stage I GC patients. In conclusion, AKR1B10 overexpression may be an independent prognostic factor for worse survival in GC patients who underwent gastrectomy with D2 lymph node dissection. Full article
(This article belongs to the Special Issue Novel Biomarkers in Gastrointestinal Malignancies)
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