| 21. |
- Zhang, Hong, 1957-, et al.
(author)
-
Upregulation of nucleoporin 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma
- 2016
-
In: International Journal of Clinical and Experimental Medicine. - : e-Century Publishing. - 1940-5901. ; 9:5, s. 8399-8404
-
Journal article (peer-reviewed)abstract
- Nucleoporin 88 (Nup 88) is a component of the nuclear pore complexes (NPCs) that mediates nucleocytoplasmic trafficking of macromolecules, Nup 88 has been reported to be up-regulated in a wide variety of malignancies. Studies show that overexpression of this antigen is associated with the development, agressiveness, differentiation and prognosis in some tumours. Since no study has been carried out in the relationship between the Nup 88 expression and clinicopathological features in the patients with oral squamous cell carcinoma (OSCC), this study aimed to determine Nup 88 expression in OSCC and its clinicopathological significance. Nup 88 expression was examined by immunohistochemistry in 20 normal oral mucosa specimens and 83 OSCC tissues. The frequency of positive Nup 88 expression was gradually increased from normal oral mucosa (10%) to primary OSCC (40%, P=0.012). The Nup 88 positive rate in OSCC patient with nodal metastasis was significantly higher than those without nodal metastasis (64% vs. 21%, P=0.000085). The frequency of positive Nup 88 expression was significantly different between worse and better differentiation (80 vs. 27%, P=0.000024). Nup 88 expression was not related to the patients' gender, age, location and tumour size (P>0.05). In conclusion, Nup 88 may play an important role in tumorigenesis in oral squamous cell carcinoma. Upregulation of Nup 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma.
|
|
| 22. |
- Zhang, Xueli, 1991-
(author)
-
Biomarkers for Diagnosis, Therapy and Prognosis in Colorectal Cancer : a study from databases, machine learning predictions to laboratory confirmations
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Early diagnosis and better therapy response have been believed to be associated with better prognosis. CRC biomarkers are considered as precise indicators for the early diagnosis and better therapy response. It is, therefore, of importance to find out, analyze and evaluate the CRC biomarkers to further provide the more precis evidence for predicting novel potential biomarkers and eventually to improve early diagnosis, personalized therapy and prognosis for CRC.In this study, we started with creating and establishing a CRC biomarker database. (CBD: http://sysbio.suda.edu.cn/CBD/index.html) In the CBD database, there were 870 reported CRC biomarkers collected from the published articles in PubMed. In this version of the CBD, CRC biomarker data was carefully collected, sorted, displayed, and analyzed. The major applications of the CBD are to provide 1) the records of CRC biomarkers (DNA, RNA, protein and others) concerning diagnosis, treatment and prognosis; 2) the basic and clinical research information concerning the CRC biomarkers; 3) the primary results for bioinformatics and biostatics analysis of the CRC biomarkers; 4) downloading/uploading the biomedicine information for CRC biomarkers.Based on our CBD and other public databases, we further analyzed the presented CRC biomarkers (DNAs, RNAs, proteins) and predicted novel potential multiple biomarkers (the combination of single biomarkers) with biological networks and pathways analysis for diagnosis, therapy response and prognosis in CRC. We found several hub biomarkers and key pathways for the diagnosis, treatment and prognosis in CRC. Receiver operating characteristic (ROC) test and survival analysis by microarray data revealed that multiple biomarkers could be better biomarkers than the single biomarkers for the diagnosis and prognosis of CRC.There are 62 diagnosis biomarkers for colon cancer in our CBD. In the previous studies, we found these present biomarkers were not enough to improve significantly the diagnosis of colon cancer. In order to find out novel biomarkers for the colon cancer diagnosis, we have performed /machine learning (ML) techniques such as support vector machine (SVM) and regression tree to predict candidate to discover diagnostic biomarkers for colon cancer. Based on the protein-protein interaction (PPI) network topology features of the identified biomarkers, we found 12 protein biomarkers which were considered as the candidate colon cancer diagnosis biomarkers. Among these protein biomarkers Chromogranin-A (CHGA) was the most powerful biomarker, which showed good performance in bioinformatics test and Immunohistochemistry(IHC). We are now expanding this study to CRC.Expression of CHGA protein in colon cancer was further verified with a novel logistic regressionbased meta-analysis, and convinced as a valuable diagnostic biomarker as compared with the typical diagnostic biomarkers, such as TP53, KRAS and MKI67.microRNAs (miRNAs/miRs) have been considered as potential biomarkers. A novel miRNA-mRNA interaction network-based model was used to predict miRNA biomarkers for CRC and found that miRNA-186-5p, miRNA-10b-5p and miRNA-30e-5p might be the novel biomarkers for CRC diagnosis. In conclusion, we have created a useful CBD database for CRC biomarkers and provided detailed information for how to use the CBD in CRC biomarker investigations. Our studies have been focusing on the biomarkers in diagnosis, therapy and prognosis. Based on our CBD and other powerful cancer associated databases, ML has been used to analyze the characteristics of the CRC biomarkers and predict novel potential CRC biomarkers. The predicted potential biomarkers were further confirmed at biomedical laboratory.
|
|
| 23. |
- Zhang, Xueli, 1990-, et al.
(author)
-
CBD : a biomarker database for colorectal cancer
- 2018
-
In: Database. - : Oxford University Press. - 1758-0463.
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.
|
|
| 24. |
- Zhang, Xueli, 1990-, et al.
(author)
-
Chromogranin-A Expression as a Novel Biomarker for Early Diagnosis of Colon Cancer Patients
- 2019
-
In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 20:12
-
Journal article (peer-reviewed)abstract
- Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein-protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.
|
|
| 25. |
- Zhang, Xueli, et al.
(author)
-
Loss of CHGA Protein as a Potential Biomarker for Colon Cancer Diagnosis : A Study on Biomarker Discovery by Machine Learning and Confirmation by Immunohistochemistry in Colorectal Cancer Tissue Microarrays
- 2022
-
In: Cancers. - Basel, Switzerland : MDPI. - 2072-6694. ; 14:11
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The incidence of colorectal cancers has been constantly increasing. Although the mortality has slightly decreased, it is far from satisfaction. Precise early diagnosis for colorectal cancer has been a great challenge in order to improve patient survival.PATIENTS AND METHODS: We started with searching for protein biomarkers based on our colorectal cancer biomarker database (CBD), finding differential expressed genes (GEGs) and non-DEGs from RNA sequencing (RNA-seq) data, and further predicted new biomarkers of protein-protein interaction (PPI) networks by machine learning (ML) methods. The best-selected biomarker was further verified by a receiver operating characteristic (ROC) test from microarray and RNA-seq data, biological network, and functional analysis, and immunohistochemistry in the tissue arrays from 198 specimens.RESULTS: There were twelve proteins (MYO5A, CHGA, MAPK13, VDAC1, CCNA2, YWHAZ, CDK5, GNB3, CAMK2G, MAPK10, SDC2, and ADCY5) which were predicted by ML as colon cancer candidate diagnosis biomarkers. These predicted biomarkers showed close relationships with reported biomarkers of the PPI network and shared some pathways. An ROC test showed the CHGA protein with the best diagnostic accuracy (AUC = 0.9 in microarray data and 0.995 in RNA-seq data) among these candidate protein biomarkers. Furthermore, immunohistochemistry examination on our colon cancer tissue microarray samples further confirmed our bioinformatical prediction, indicating that CHGA may be used as a potential biomarker for early diagnosis of colon cancer patients.CONCLUSIONS: CHGA could be a potential candidate biomarker for diagnosing earlier colon cancer in the patients.
|
|
| 26. |
- Zhang, Xueli, 1990-, et al.
(author)
-
Novel MicroRNA Biomarkers for Colorectal Cancer Early Diagnosis and 5-Fluorouracil Chemotherapy Resistance but Not Prognosis : A Study from Databases to AI-Assisted Verifications
- 2020
-
In: Cancers. - : MDPI. - 2072-6694. ; 12:2
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis.
|
|
| 27. |
- Zhang, Xueli, 1990-, et al.
(author)
-
Potential Applications of DNA, RNA and Protein Biomarkers in Diagnosis, Therapy and Prognosis for Colorectal Cancer : A Study from Databases to AI-Assisted Verification
- 2019
-
In: Cancers. - : MDPI. - 2072-6694. ; 11:2
-
Journal article (peer-reviewed)abstract
- In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.
|
|
| 28. |
- Adell, Gunnar C. E., 1953-, et al.
(author)
-
Apoptosis in rectal carcinoma : Prognosis and recurrence after preoperative radiotherapy
- 2001
-
In: Cancer. - 0008-543X .- 1097-0142. ; 91:10, s. 1870-1875
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Rectal carcinoma is common, with considerable local recurrence and death rates. Preoperative radiotherapy and refined surgical techniques can improve local control. The aim of this study was to investigate the interaction between apoptosis and the outcome of rectal carcinoma, with and without short-term preoperative radiotherapy.METHODS: Specimens were from 162 patients from the Southeast Swedish Health Care region included in the Swedish Rectal Cancer Trial between 1987-1990. New sections from the paraffin blocks of the preoperative biopsies and the surgical specimens were examined for apoptosis using the terminal deoxynucleotidyl transferase mediated digoxigenin nick end labeling (TUNEL) method.RESULTS: The mean percentage of apoptotic cells was 0.3% (0-4%) and 1.1% (0-14.5%) for the preoperative biopsy and the surgical specimen, respectively. The authors analyzed the surgical specimens from nonirradiated patients and divided them into three groups by apoptotic index (AI) as follows: 0%, 0-1%, and > 1%. A high AI was associated with a decreased local recurrence rate compared with an intermediate or a low AI (P = 0.024). There was no significant relation between AI and survival. There was a significant reduction in the local recurrence rate for irradiated patients compared with the nonirradiated in the low (P = 0.015) and intermediate (P = 0.038) AI groups. In the high AI group, there were few recurrences and no significant difference was observed between irradiated and nonirradiated patients. The relative risk of death from rectal carcinoma in Dukes A-C patients was not significantly decreased by radiotherapy, but, in the intermediate AI group, there was a trend (P = 0.08) in favor of the irradiated patients.CONCLUSION: A high AI in rectal carcinoma indicated a decreased local recurrence rate.
|
|
| 29. |
- Adell, Gunnar, 1953-, et al.
(author)
-
Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer
- 2001
-
In: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 50:3, s. 659-663
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival.PURPOSE: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy.Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen.MATERIALS: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990.RESULTS: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p = 0.03), with a trend toward improved disease-free survival (p = 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates.CONCLUSION: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.
|
|
| 30. |
- Andreyev, HJN, et al.
(author)
-
Kirsten ras mutations in patients with colorectal cancer : The 'RASCAL II' study
- 2001
-
In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 85:5, s. 692-696
-
Journal article (peer-reviewed)abstract
- Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P=0.004, HR 1.3) and overall survival (P=0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P=0.008, HR 1.5, overall survival P=0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P=0.46, HR 1.12, overall survival P=0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. ⌐ 2001 Cancer Research Campaign.
|
|
