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The Research of Biomarkers in Colorectal Cancer and Gastric Cancer
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The Research of Biomarkers in Colorectal Cancer and Gastric Cancer

A topical collection in Cells (ISSN 2073-4409). This collection belongs to the section "Cellular Pathology".

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Editors

Prof. Dr. Jaw-Yuan Wang

E-Mail Website
Guest Editor
1. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: precision medicine in colorectal cancer; precision medicine in gastric cancer; cancer biomarkers; molecular oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Hsiang-Lin Tsai

E-Mail Website
Co-Guest Editor
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: Colorectal cancer; Oncological nutrition; mini-invasive surgery; surgical oncology; tailored therapy
Prof. Dr. Hideki Ueno

E-Mail Website
Co-Guest Editor
Department of Surgery National Defense Medical College, Tokorozawa, Japan
Interests: adaptive immune system; the major immunological protection mechanism; antigen-specific immune response
Dr. Chi Chun Wong

E-Mail Website
Co-Guest Editor
Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Interests: gastrointestinal cancer; genetics, epigenetics; microbiome
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Worldwide, colorectal cancer (CRC) is the second most commonly diagnosed cancer in men and the third most commonly diagnosed in women. In 2018, 1.8 million new CRC cases, with more than 860,000 deaths, were estimated. Based on GLOBOCAN 2018 data, gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer, with an estimated 783,000 deaths in 2018. CRC and GC are the two major public health problems worldwide. Early cancer detection, pretherapeutic responsiveness prediction, and an optimal postoperative surveillance strategy are the hallmarks for successful GI cancer treatment. The approval of novel therapies for metastatic GI cancer (mGIC) has led to important improvements in patient outcomes. Despite the multitude of treatments available, outcomes and toxicity with each regimen can vary markedly from patient to patient. Therefore, it is still necessary to increase the individualization of treatments based on tumor genetic profiles to optimize efficacy, while minimizing toxicity. As such, there is currently great focus on the discovery and validation of novel biomarkers in mGIC, with many new potential prognostic and predictive markers being identified alongside developments in molecular profiling technologies. Newer technologies such as ctDNA, miRNA, next-generation sequencing (NGS) and customized genetic panels have highlighted their potential predictive and prognostic roles. There is a clear need for evidence-based recommendations to guide the use of validated and emerging biomarkers in clinical practice. Furthermore, the future focus on the development of emerging biomarkers for the medical unmet needs of GI cancer patients is mandatory.

Prof. Dr. Jaw-Yuan Wang
Guest Editor

Dr. Hsiang-Lin Tsai
Prof. Dr. Hideki Ueno
Prof. Dr. CC. Dennis Wong
Co-Guest Editors

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Keywords

  • biomarkers landscape
  • colorectal cancer
  • gastric cancer
  • personalized medicine
  • early detection
  • postoperative surveillance

Published Papers (7 papers)

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2022

20 pages, 1260 KiB  
Review
Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer
by Jen-Pin Chuang, Hsiang-Lin Tsai, Po-Jung Chen, Tsung-Kun Chang, Wei-Chih Su, Yung-Sung Yeh, Ching-Wen Huang and Jaw-Yuan Wang
Cells 2022, 11(23), 3744; https://doi.org/10.3390/cells11233744 - 23 Nov 2022
Cited by 14 | Viewed by 2773
Abstract
Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced [...] Read more.
Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC. Full article
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20 pages, 3456 KiB  
Article
Upregulation of YKL-40 Promotes Metastatic Phenotype and Correlates with Poor Prognosis and Therapy Response in Patients with Colorectal Cancer
by Mariangela De Robertis, Maria Raffaella Greco, Rosa Angela Cardone, Tommaso Mazza, Flaviana Marzano, Nikolay Mehterov, Maria Kazakova, Nikolay Belev, Apollonia Tullo, Graziano Pesole, Victoria Sarafian and Emanuela Signori
Cells 2022, 11(22), 3568; https://doi.org/10.3390/cells11223568 - 11 Nov 2022
Cited by 12 | Viewed by 2431
Abstract
YKL-40 is a heparin- and chitin-binding glycoprotein that belongs to the family of glycosyl hydrolases but lacks enzymatic properties. It affects different (patho)physiological processes, including cancer. In different tumors, YKL-40 gene overexpression has been linked to higher cell proliferation, angiogenesis, and vasculogenic mimicry, [...] Read more.
YKL-40 is a heparin- and chitin-binding glycoprotein that belongs to the family of glycosyl hydrolases but lacks enzymatic properties. It affects different (patho)physiological processes, including cancer. In different tumors, YKL-40 gene overexpression has been linked to higher cell proliferation, angiogenesis, and vasculogenic mimicry, migration, and invasion. Because, in colorectal cancer (CRC), the serological YKL-40 level may serve as a risk predictor and prognostic biomarker, we investigated the underlying mechanisms by which it may contribute to tumor progression and the clinical significance of its tissue expression in metastatic CRC. We demonstrated that high-YKL-40-expressing HCT116 and Caco2 cells showed increased motility, invasion, and proliferation. YKL-40 upregulation was associated with EMT signaling activation. In the AOM/DSS mouse model, as well as in tumors and sera from CRC patients, elevated YKL-40 levels correlated with high-grade tumors. In retrospective analyses of six independent cohorts of CRC patients, elevated YKL-40 expression correlated with shorter survival in patients with advanced CRC. Strikingly, high YKL-40 tissue levels showed a predictive value for a better response to cetuximab, even in patients with stage IV CRC and mutant KRAS, and worse sensitivity to oxaliplatin. Taken together, our findings establish that tissue YKL-40 overexpression enhances CRC metastatic potential, highlighting this gene as a novel prognostic candidate, a predictive biomarker for therapy response, and an attractive target for future therapy in CRC. Full article
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10 pages, 691 KiB  
Article
Assessment of a Serum Microrna Risk Score for Colorectal Cancer among Participants of Screening Colonoscopy at Various Stages of Colorectal Carcinogenesis
by Janhavi R. Raut, Megha Bhardwaj, Tobias Niedermaier, Kaya Miah, Petra Schrotz-King and Hermann Brenner
Cells 2022, 11(15), 2462; https://doi.org/10.3390/cells11152462 - 8 Aug 2022
Cited by 2 | Viewed by 2034
Abstract
We recently derived and validated a serum-based microRNA risk score (miR-score) which predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a large population-based cohort. Here, we aimed to assess and compare the distribution of the miR-score [...] Read more.
We recently derived and validated a serum-based microRNA risk score (miR-score) which predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a large population-based cohort. Here, we aimed to assess and compare the distribution of the miR-score among participants of screening colonoscopy at various stages of colorectal carcinogenesis. MicroRNAs (miRNAs) were profiled by quantitative-real-time-polymerase-chain-reaction in the serum samples of screening colonoscopy participants with CRC (n = 52), advanced colorectal adenoma (AA, n = 100), non-advanced colorectal adenoma (NAA, n = 88), and participants free of colorectal neoplasms (n = 173). The mean values of the miR-score were compared between groups by the Mann–Whitney U test. The associations of the miR-score with risk for colorectal neoplasms were evaluated using logistic regression analyses. MicroRNA risk scores were significantly higher among participants with AA than among those with NAA (p = 0.027) and those with CRC (p = 0.014), whereas no statistically significant difference was seen between those with NAA and those with no colorectal neoplasms (p = 0.127). When comparing adjacent groups, miR-scores were inversely associated with CRC versus AA and positively associated with AA versus NAA [odds ratio (OR), 0.37 (95% confidence interval (CI), 0.16–0.86) and OR, 2.22 (95% CI, 1.06–4.64) for the top versus bottom tertiles, respectively]. Our results are consistent with the hypothesis that a high miR-score may be indicative of an increased CRC risk by an increased tendency of progression from non-advanced to advanced colorectal neoplasms, along with a change of the miR-patterns after CRC manifestation. Full article
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20 pages, 6045 KiB  
Article
High Levels of Tumor miR-187-3p—A Potential Tumor-Suppressor microRNA—Are Correlated with Poor Prognosis in Colorectal Cancer
by Lui Ng, Timothy Ming-Hun Wan, Deepak Narayanan Iyer, Zheng Huang, Ryan Wai-Yan Sin, Abraham Tak-Ka Man, Xue Li, Dominic Chi-Chung Foo, Oswens Siu-Hung Lo and Wai-Lun Law
Cells 2022, 11(15), 2421; https://doi.org/10.3390/cells11152421 - 5 Aug 2022
Cited by 3 | Viewed by 2606
Abstract
Background: The microRNA miR-187-3p plays antitumor roles in a variety of cancers. We and others have previously identified miR-187-3p as a potential tumor suppressor in colorectal cancer (CRC), but there are also reports revealing that high miR-187-3p levels are associated with poor prognosis [...] Read more.
Background: The microRNA miR-187-3p plays antitumor roles in a variety of cancers. We and others have previously identified miR-187-3p as a potential tumor suppressor in colorectal cancer (CRC), but there are also reports revealing that high miR-187-3p levels are associated with poor prognosis among CRC patients. This study further investigated the clinicopathological significance of miR-187-3p in CRC. Methods: MiR-187-3p levels in paired polyp/CRC/normal specimens or primary CRC/liver metastasis specimens were determined by qPCR, and correlated with the patient’s clinicopathological and postoperative survival data. The clinical findings were validated using our validation cohort and data obtained from the TCGA or GEO databases. The functional effects of miR-187-3p were investigated through its overexpression in CRC cell lines. Results: MiR-187-3p was significantly repressed in colorectal polyps and CRC when compared to adjacent normal tissue. Overexpression of miR-187-3p in CRC cell lines impaired colony formation, cell migration, and invasion, and induced chemosensitivity. Clinical analysis revealed that despite miR-187-3p being repressed in CRC, high tumor miR-187-3p levels were positively correlated with tumor stage and disease recurrence. Further analysis showed that miR-187-3p levels were lower in metastatic specimens when compared to paired primary CRC, suggesting that high tumor miR-187-3p levels resulted from the dissemination of metastatic tumor cells. Tumor miR-187-3p levels were positively correlated with peripheral inflammation-related blood markers. Finally, SPRY1 was identified as a novel target gene of miR-187-3p, and was involved in miR-187-3p-impaired CRC metastasis. Conclusions: This study demonstrated that in spite of its repression and role as a tumor suppressor in CRC, high levels of miR-187-3p in tumors were correlated with poor prognosis and higher levels of peripheral inflammation-related blood markers. Full article
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13 pages, 1437 KiB  
Article
High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients
by Lui Ng, Hung-Sing Li, Abraham Tak-Ka Man, Ariel Ka-Man Chow, Dominic Chi-Chung Foo, Oswens Siu-Hung Lo, Roberta Wen-Chi Pang and Wai-Lun Law
Cells 2022, 11(11), 1852; https://doi.org/10.3390/cells11111852 - 6 Jun 2022
Cited by 1 | Viewed by 2461
Abstract
Background: Several studies have demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers. This study investigated the clinical significance of CBX8 gene expression, a cancer stemness-related gene, in tumor and [...] Read more.
Background: Several studies have demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers. This study investigated the clinical significance of CBX8 gene expression, a cancer stemness-related gene, in tumor and NAT tissue of colorectal cancer (CRC) patients. Methods: The gene level of CBX8 in paired CRC and NAT specimens from 95 patients was determined by quantitative PCR. CBX8 protein level in CRC and NAT specimens from 66 patients was determined by immunohistochemistry. CBX8 gene and protein levels were correlated with the patients’ clinicopathological parameters and circulatory immune cell profiles. The association between CBX8 and pluripotency-associated genes was analyzed using the TCGA database. Results: NAT CBX8 gene level positively correlated with TNM stage, tumor invasion, lymph node metastasis and distant metastasis, indicating its association with tumor progression and metastasis. There was no correlation between NAT CBX8 protein level and clinicopathological parameters. Moreover, a high level of CBX8 gene and protein in NAT both correlated with poor DFS and OS. There was an inverse correlation between CBX8 gene level and post-operative platelet counts and platelet to lymphocyte level, suggesting its association with systematic inflammation. Finally, TCGA analysis showed that CBX8 level was correlated with a couple of pluripotency-associated genes, supporting its association with cancer stemness. Conclusions: High NAT CBX8 is a poor prognostic factor for tumor progression and survival in CRC patients. Full article
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17 pages, 936 KiB  
Review
Biomarkers of Favorable vs. Unfavorable Responses in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy
by Hsin-Hua Lee, Chien-Hung Chen, Yu-Hsiang Huang, Cheng-Han Chiang and Ming-Yii Huang
Cells 2022, 11(10), 1611; https://doi.org/10.3390/cells11101611 - 11 May 2022
Cited by 6 | Viewed by 3382
Abstract
Colorectal cancer is the second leading cause of cancer death globally. The gold standard for locally advanced rectal cancer (LARC) nowadays is preoperative concurrent chemoradiation (CCRT). Approximately three quarters of LARC patients do not achieve pathological complete response and hence suffer from relapse, [...] Read more.
Colorectal cancer is the second leading cause of cancer death globally. The gold standard for locally advanced rectal cancer (LARC) nowadays is preoperative concurrent chemoradiation (CCRT). Approximately three quarters of LARC patients do not achieve pathological complete response and hence suffer from relapse, metastases and inevitable death. The exploration of trustworthy and timely biomarkers for CCRT response is urgently called for. This review focused upon a broad spectrum of biomarkers, including circulating tumor cells, DNA, RNA, oncogenes, tumor suppressor genes, epigenetics, impaired DNA mismatch repair, patient-derived xenografts, in vitro tumor organoids, immunity and microbiomes. Utilizing proper biomarkers can assist in categorizing appropriate patients by the most efficient treatment modality with the best outcome and accompanied by minimal side effects. The purpose of this review is to inspect and analyze accessible data in order to fully realize the promise of precision oncology for rectal cancer patients. Full article
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12 pages, 1509 KiB  
Article
Genomic and Metabolomic Landscape of Right-Sided and Left-Sided Colorectal Cancer: Potential Preventive Biomarkers
by Ming-Wei Su, Chung-Ke Chang, Chien-Wei Lin, Hou-Wei Chu, Tsen-Ni Tsai, Wei-Chih Su, Yen-Cheng Chen, Tsung-Kun Chang, Ching-Wen Huang, Hsiang-Lin Tsai, Chang-Chieh Wu, Huang-Chi Chou, Bei-Hao Shiu and Jaw-Yuan Wang
Cells 2022, 11(3), 527; https://doi.org/10.3390/cells11030527 - 3 Feb 2022
Cited by 9 | Viewed by 3047
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence and mortality rates of CRC are significantly higher in Taiwan than in other developed countries. Genes involved in CRC tumorigenesis differ depending on whether the tumor occurs on the left or [...] Read more.
Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence and mortality rates of CRC are significantly higher in Taiwan than in other developed countries. Genes involved in CRC tumorigenesis differ depending on whether the tumor occurs on the left or right side of the colon, and genomic analysis is a keystone in the study and treatment of CRC subtypes. However, few studies have focused on the genetic landscape of Taiwanese patients with CRC. This study comprehensively analyzed the genomes of 141 Taiwanese patients with CRC through whole-exome sequencing. Significant genomic differences related to the site of CRC development were observed. Blood metabolomic profiling and polygenic risk score analysis were performed to identify potential biomarkers for the early identification and prevention of CRC in the Taiwanese population. Our findings provide vital clues for establishing population-specific treatments and health policies for CRC prevention in Taiwan. Full article
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