RNA sequencing and bioinformatics analysis have identified MAST1 as a potential biomarker and therapeutic target for cervical cancer
BackgroundCervical cancer (CC) is a widely recognized malignant tumor that imposes a substantial economic burden on the global healthcare system. Currently, treatment options for patients with advanced metastatic and recurrent CC are suboptimal. Therefore, further in-depth research into the characteristics of CC occurrence and metastasis may provide additional reference indicators for patient diagnosis, treatment, and prognosis. This study aims to screen differential genes in CC via transcriptome sequencing and bioinformatics analysis, verify the role of microtubule-associated serine/threonine kinase 1 (MAST1) in CC, and explore its underlying molecular mechanisms, providing a basis for CC diagnosis and treatment.MethodsIn this study, we performed transcriptome sequencing on three cases of CC and adjacent normal tissues to understand the differences in gene expression profiles between cancerous and adjacent tissues. Bioinformatics methods were used to functionally enrich the differentially expressed genes, and these data were further analyzed to screen for the differential gene MAST1. The expression of the gene in tumor and adjacent normal tissues was detected through reverse transcription quantitative polymerase chain reaction (RT-qPCR), protein immunoblotting, and immunohistochemistry (IHC). Small interfering RNA (siRNA) was designed to construct a knockdown CC cell line, and the cell migration ability was verified through Transwell assays, and the expression of pathway-related proteins was detected by Western blotting.ResultsTranscriptome sequencing revealed that 40 genes were significantly upregulated, and 62 genes were significantly downregulated in CC tissues. Gene Ontology (GO) analysis indicated that the differentially expressed genes (DEGs) were predominantly related to the extracellular matrix, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these genes were mainly enriched in pathways associated with glutamatergic synapses, axon guidance, and cancer. Combining The Cancer Genome Atlas (TCGA) sequencing results, five highly expressed genes (MISP, MAST1, MUC13, OLR1, and PAQR4) were selected. RT-qPCR, western blot, and IHC results confirmed that MAST1 expression was significantly higher in cancer tissues than in adjacent normal tissues. In vitro cell experiments showed that the knockdown of MAST1 in Hela cells reduced cell invasion ability and downregulated the p-AKT and p-P38 signaling pathways.ConclusionsThis study contributes to a deeper understanding of the role of MAST1 in the invasion of CC, affecting the occurrence and development of malignant tumors in the cervix through the p-AKT and p-P38 classical signaling pathways, and can serve as a potential therapeutic target for patients with CC.
- Research Article
- 10.3760/cma.j.issn.1006-9801.2014.04.001
- Apr 28, 2014
Objective To illustrate the composition ratio of ERβ isoforms in paired cancerous and adjacent normal tissues from breast cancer patients.Methods Eighty-seven pairs of cancerous and adjacent normal tissues were obtained from breast cancer patients.RT-qPCR was used to determine the relative mRNA expression levels of ERβ isoforms (ER[β1,ERβ2 and ERβ5),and the composition ratios of ERβ isoforms were analyzed.Results The expression levels of all tested ERβ isoforms (ERβ1,ERβ2 and ERβ5) in breast cancer tissues were much lower than those in adjacent normal breast tissues (P < 0.01).Isoform ratio analysis showed that ERβ5 was the dominant isoform in both cancerous and adjacent normal tissues with a positive detection rate of 54.02 % and 75.84 %,respectively.Meanwhile,ERβ1 had the lowest detection rate (9.74 % and 6.77 % in cancerous and adjacent normal tissues,respectively).The positive rates for both ERβ1 and ERβ2 were much lower in adjacent normal tissues than those in cancer tissues (Z =-2.24,P =0.025 and Z =-4.85,P < 0.01,separately),while more cancerous tissues were ERβ5-positive in comparison to adjacent normal tissues (Z =-5.32,P < 0.01).Conclusions The expression levels of all the ERβ isoforms are differentially down-regulated with significant alterations in their composition ratios during breast carcinogenesis.Further understanding on molecular mechanisms underlying the differential down-regulation of ER[β isoforms will shed new light on breast carcinogenesis. Key words: Breast neoplasms; Estrogen receptor beta; Protein isoforms; Composition rate
- Research Article
- 10.3760/cma.j.issn.1673-9752.2016.03.012
- Mar 20, 2016
- Chinese Journal of Digestive Surgery
Objective To investigate the expressions and relationship between lysine-specific demethylase 1 (LSD1) and E-cadherin protein in gastric cancer tissues and adjacent normal tissues, and the correlation with the clinicopathological features and prognosis of patients with gastric cancer. Methods The case-control study was adopted. The gastric cancer tissues and adjacent normal tissues were collected by surgical resection from 80 patients with gastric cancer who were admitted to the Xiangya Hospital of Central South University from June 2008 to June 2009. Expressions of LSD1 and E-cadherin protein were detected by immunohistochemistry (IHC). The follow-up of telephone interview was performed to detect survival of patients till June 2015. Relationships between the expressions of LSD1 and E-cadherin protein and clinicopathological features or prognosis of patients were analyzed. Comparison of count data and correlation were analyzed by the chi-square test and Spearman rank correlation analysis. Survival curve was drawn using the Kaplan-Meier method, and survival analysis was done using the Log-rank test. Results Expressions of LSD1 in cancer tissues and adjacent normal tissues were located at the cell nucleus. The positive expression rate of LSD1 was 67.5%(54/80) and 43.8%(35/80) in cancer tissues and adjacent normal tissues, respectively, with a significant difference (χ2=9.141, P<0.05). Expressions of E-cadherin protein in cancer tissues and adjacent normal tissues were located at the cell membrane and cytoplasm. The positive expression rate of E-cadherin was 63.8%(51/80) and 81.3%(65/80) in cancer tissues and adjacent normal tissues, respectively, with a significant difference (χ2=6.140, P<0.05). The positive expression rate of LSD1 was 83.3%(25/30), 76.0%(19/25) and 40.0%(10/25) in the low-, moderate- and high-differentiated tumors, 37.5%(6/16), 72.7%(16/22), 71.9%(23/32) and 90.0%(9/10) in the Ⅰ, Ⅱ, Ⅲ and Ⅳ stages of TNM stage, 36.4%(4/11) and 72.5%(50/69) in patients without and with lymph node metastasis, respectively, showing significant differences (χ2=12.870, 9.425, 4.111, P<0.05). The positive expression rate of E-cadherin protein was 53.3%(16/30), 56.0% (14/25) and 84.0%(21/25) in the low-, moderate- and high-differentiated tumors, 75.0%(12/16), 63.6%(14/22), 71.9%(23/32) and 20.0% (2/10) in the Ⅰ, Ⅱ, Ⅲ and Ⅳ stages of TNM stage, 100.0%(11/11)and 58.0%(40/69) in patients without and with lymph node metastasis, 70.0%(49/70) and 20.0%(2/10) in patients without and with distant metastasis, respectively, showing significant differences (χ2=6.494, 10.073, 5.547, 7.426, P<0.05). There was a negative correlation in expressions between LSD1 and E-cadherin protein (r=-0.355, P<0.05). The survival time and 5-year overall survival rate of patients with positive and negative expressions of LSD1 were (36.9±2.5)months and 31.1%, (47.4±3.4)months and 56.0%, respectively, showing a significant difference (χ2=4.550, P<0.05). The survival time and 5-year overall survival rate of the patients with positive and negative expressions of E-cadherin protein were (44.0±2.5)months and 46.7%, (32.6±3.5)months and 24.9%, respectively, showing a significant difference (χ2=7.306, P<0.05). Conclusions Positive expression of LSD1 in gastric cancer tissues is higher than that in adjacent normal tissues. There are increased expression of LSD1 and reduced expression of E-cadherin protein in low-differentiated gastric cancer tissues and high TNM stage, showing a negative correlation between them. Positive expression of LSD1 and negative expression of E-cadherin protein may indicate a poor prognosis. Key words: Gastric neoplasms; Epigenetic; Lysine-specific demethylase 1; E-cadherin protein; Prognosis
- Research Article
18
- 10.3892/ol.2015.3884
- Nov 6, 2015
- Oncology Letters
The present study aimed to determine the expression of stem cell markers Nanog compared with PSCA in gastric cancer tissues and adjacent normal tissues, and to investigate the association between tumor stem cells and initiation, progression, metastasis, and prognosis of gastric cancer. One hundred chemotherapy- and radiotherapy-naive patients with pathologically confirmed gastric cancer were enrolled from the General Surgery Department and Surgical Oncology Department of the Affiliated Hospital of Inner Mongolia Medical University (Hohhot, P.R. China), between October 2011 and June 2013. Surgically resected specimens of cancer tissues and adjacent normal tissues (>5 cm from the boundary of cancerous component) were collected. The mRNA expression levels of Nanog and PSCA in those tissues was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between the expression of stem cell markers Nanog and PSCA in gastric cancer tissues and clinicopathological factors was analyzed. The qPCR results demonstrated that the relative expression of Nanog was increased in gastric cancer tissues compared with in the adjacent tissues (P<0.05); and relative expression of PSCA was reduced in gastric cancer tissues compared with adjacent tissues (P<0.05). The expression of Nanog and PSCA in gastric cancer tissues was associated with tumor differentiation. The expression of Nanog was increased in poorly-differentiated and undifferentiated tumors compared with moderately- and well-differentiated tumors (P<0.05). The expression of PSCA was reduced in poorly differentiated and undifferentiated tumors compared with moderately- and well-differentiated tumors (P<0.05). However, the expression of Nanog and PSCA was not associated with age, gender, tumor size, TNM stage, depth of invasion, or lymph node metastasis. Therefore, Nanog and PSCA may have potential as molecular markers to reflect the differentiation status of gastric cancer.
- Research Article
- 10.3760/cma.j.issn.1008-1372.2019.12.016
- Dec 20, 2019
- Journal of Chinese Physician
Objective To investigate the expression of phosphorylated protein kinase B (PKB/AKT) and spleen tyrosine protein kinase (Syk) in different tumor node metastasis (TNM) stages of gastric cancer patients. Methods From January 2015 to April 2018, 82 patients with gastric cancer confirmed by gastroscopy and surgical pathology were enrolled in this study. All patients were selected for cancer tissue, and 30 patients were randomly selected from normal gastric mucosa at 5 cm adjacent to the tumor. Immunohistochemistry was used to detect the expression of PKB/AKT and Syk protein. To compare the expression of PKB/AKT and Syk in gastric cancer and adjacent normal tissues, and to analyze the relationship between PKB/AKT and Syk expression and clinicopathological features in gastric cancer tissues, and the correlation between PKB/AKT and Syk and TNM staging of gastric cancer patients. Results The positive expression rate of PKB/AKT in gastric cancer tissues was higher than that in adjacent tissues (P<0.05). The positive expression rate of Syk was lower than that in adjacent tissues (P<0.05). PKB/Akt and Syk gene expression in gastric cancer were related to histological grade, tumor infiltration, TNM staging, lymph node metastasis and distant metastasis (P<0.05), and the expression of PKB/AKT was significantly increased with the increase of TNM staging in gastric cancer patients, and the positive expression of Syk was significantly decreased (P<0.05). Conclusions PKB/AKT is positively correlated with TNM staging of gastric cancer patients. Syk is negatively correlated with TNM staging of gastric cancer patients. The clinical expression of PKB/AKT and Syk can be used to determine the TNM staging of gastric cancer, which provides a strong basis for tumor treatment. It is of great significance in treatment. Key words: Stomach neoplasms; Neoplasm staging; Phosphorylation; Proto-oncogene proteins c-akt; Syk kinase
- Research Article
- 10.3760/cma.j.issn.1674-1935.2015.05.010
- Oct 20, 2015
Objective To confirm the main pathway of chemokine-chemokine receptor which mediates the accumulation of regulatory T cell (Treg) in pancreatic cancer. Methods The concentrations of protein of FOXP3 and chemokines of CCL2, CCL3, CCL5, CCL17, CXCL8 in human and mouse pancreatic cancer and adjacent normal pancreatic tissue were measured by the method of enzyme-linked immunosorbent assay (ELISA). The receptor of chemokine CCL5 (CCR5) in human and mouse pancreatic cancer were determined by the immunofluorescent stain. Results The concentration of FOXP3 protein in human pancreatic cancer and adjacent normal pancreatic tissue as (487.5±534.1) and (162.6±42.0) pg/mg, respectively, while they were (84.6±54.1) and (14.4±7.6)pg/mg, respectively in mouse. The concentration of FOXP3 protein were significantly higher in pancreatic cancer than those in adjacent normal pancreatic tissue. The concentration of CCL2 in human pancreatic cancer and adjacent normal pancreatic tissue as (76.9±37.5), (40.8±25.5)pg/mg, and the concentration of CCL3 as (38.0±22.6), (21.3±16.5)pg/mg, and the concentration of CCL5 were (390.2±158.5), (59.1±22.8)pg/mg, and the concentration of CCL17 as (7.2±2.0), (4.1±2.4)pg/mg, and the concentration of CXCL8 as (9.3±5.5), (6.3±5.2)pg/mg. The concentration of CCL2, CCL5, CCL17 in pancreatic cancer was significantly higher than those in adjacent normal pancreatic tissue (P<0.05). The concentration of CCL2 in mouse pancreatic cancer and adjacent normal pancreatic tissue as (77.9±30.5), (43.6±16.6)pg/mg, and the concentration of CCL3 was (27.4±18.2), (14.0±4.5)pg/mg, and the concentration of CCL5 was (302.2±55.8), (64.5±30.3)pg/mg; and the concentration of CCL17 was (4.4±1.4), (2.2±1.0)pg/mg; and the concentration of CXCL8 was (55.1±55.1), (93.4±7.3)pg/mg. The concentration of CCL2, CCL5, CCL17 in pancreatic cancer were significantly higher than those in adjacent normal pancreatic tissue, and the difference between the two groups was statistically significant (P<0.05). The level of FOXP3 in pancreatic cancer was positively correlated with the concentration of chemokine CCL5 both in human and mouse pancreatic cancer. Immunofluorescent staining indicated that the FOXP3+ cells also expressed CCR5. Conclusions The CCL5-CCR5 is the main chemokine-chemokine receptor pathway mediating the accumulation of Treg cells in pancreatic cancer. Key words: Pancreatic neoplasms; Regulatory T cell; FOXP3; Chemokime
- Research Article
9
- 10.3724/abbs.2021010
- Dec 31, 2021
- Acta Biochimica et Biophysica Sinica
(.) is known to be a major risk factor for the development of gastric cancer. In recent years, increasing attention is being paid to the role of non-. (NHPHs) in this disease and the role of microorganisms in local tumor microenvironment. In this study, we aimed to compare the microbial community composition and the predicted functional profile in paired cancer and adjacent normal tissues of gastric cancer patients. Cancer tissues and adjacent normal tissues were collected from 10 patients with gastric cancer under endoscopy, and genomic DNA was extracted. The V3-V4 region of the 16S rRNA gene was amplified by PCR and paired-end sequencing was performed on the Illumina MiSeq System. The data was analyzed using QIIME 2 software. The results showed that microbial richness and diversity as well as genetic diversity are significantly lower in cancer tissues compared with adjacent normal tissues. At the phylum level, the dominant taxa are , , , and in both groups. At the genus level, some taxa, such as and, are significantly enriched in cancer tissues, while other taxa, such as , are enriched in adjacent normal tissues. Moreover, those taxa enriched in cancer tissues are associated with the synthesis and degradation of ketone bodies. In conclusion, there is a significant difference in the composition of the mucosa-related microbial communities between cancer tissues and adjacent normal tissues in patients with gastric cancer.
- Research Article
22
- 10.3892/ol.2017.6915
- Sep 8, 2017
- Oncology letters
The present study aimed to compare gene expression profiles between colorectal cancer and adjacent normal tissues, and to perform a preliminarily analysis of the key genes and underlying molecular mechanisms implicated in colorectal cancer development. Gene expression microarray chips were used to screen genes that were differently expressed between colorectal cancer and adjacent normal tissues. Approximately 1,183 genes were differentially expressed in cancer tissues compared with adjacent normal tissues (P≤0.05; fold difference, >2.0), of which 570 genes were upregulated and 613 genes were downregulated. In total, 6 upregulated genes, including keratin 23, collagen type X α1, collagen type XI α1, cell migration-inducing hyaluronan-binding protein, transforming growth factor-β1 and V-Myc avian myelocytomatosis viral oncogene homolog, and 2 downregulated genes, including channel α subunit 7 and EPH receptor A7, were selected and validated using reverse transcription-quantitative polymerase chain reaction, which exhibited results that were consistent with the microarray analysis. These 1,183 differentially expressed genes were further classified into 71 groups based on their functions using gene ontology and pathway analyses. Kyoto Encyclopedia of Genes and Genomes analysis of these upregulated or downregulated genes suggested that 23 signaling pathways were involved. The present study preliminarily screened for and identified key genes and signaling pathways that may be closely associated with colorectal cancer development. However, subsequent gene function studies are required to verify these findings.
- Research Article
- 10.29252/sjimu.26.1.132
- May 1, 2018
- Journal of Ilam University of Medical Sciences
Introduction: The molecular mechanisms involved in the development and progression of breast cancer have yet to be determined. In the present study, the proteome of cancerous beast and adjacent normal tissues were compared. Materials & Methods: In a cohort study, the cancer tissues and adjacent normal tissues were obtained from 5 female patients with ductal carcinoma in stage 3. The total protein contents of cancer and adjacent normal tissues were extracted. The protein expression levels were examined by Image Master 2D Platinum software following two-dimensional gel electrophoresis. MALDI-TOF MS/MS mass spectrometry was used for proteins identification. Findings: The constant region of Ig gamma-1 chain and beta subunit of hemoglobin were exclusively detected in the cancer and adjacent normal tissues, respectively. The expression of serum albumin and collagen VI alpha chain in the cancer tissue was significantly lower than the normal tissue (P less-than 0.05). In contrast, the expression of a single peptide matching to cytoskeletal type I and II keratin significantly increased in the cancer tissue compared to the normal tissues (P less-than 0.05). Discussion & Conclusion: As the output of our investigation, it seems that proteome of cancerous tissue is extensively different from the adjacent one. Therefore, proteomic approach might be a promising tool for monitoring breast tumorigenesis. However, this needs to be confirmed in future.
- Research Article
- 10.3760/cma.j.issn.1673-9752.2016.08.010
- Aug 20, 2016
- Chinese Journal of Digestive Surgery
Objective To investigate the expression of C-terminal tensin-like (CTEN) protein and its correlations with clinicopathological characteristics and prognosis in patients with colorectal cancer. Methods The retrospective case-control study was adopted. The clinical data of 153 patients with colorectal cancer who were admitted to the Affiliated Hospital of Jiangsu University between January 2010 and December 2012 were collected. The expression of CTEN protein were detected by immunohistochemistry. Observed indices included: (1) expression of CTEN protein was detected by immunohistochemistry. (2) Relationships between the expressions of CTEN protein and clinicopathological characteristics of patients. (3) Relationships between the expressions of CTEN protein and prognosis of patients. The follow-up of telephone interview was performed to detect survival of patients untill May 2015. Count data were analyzed using two-sided chi-square test. Survival curve was drawn using the Kaplan-Meier method, and survival analyses was done using the Log-rank test. Univariate and multivariate analyses of prognosis were done using COX regression model. Results (1) Expressions of CTEN protein in cancer tissues and adjacent tissues were located at the cytoplasms. The positive expression rate of CTEN protein was 92.16%(141/153) and 20.26%(31/153) in cancer tissues and adjacent tissues, respectively, with a statistically significant difference (χ2=160.647, P 0.05). All the 153 patients were followed up for 4.8-62.3 months with a median time of 27.5 months. The 3-year tumor-free survival (Ⅰ-Ⅲ stages) and overall survival (Ⅰ-Ⅳ stages) rates were 52.23% and 39.71% of patients with high expression of CTEN protein, 76.89% and 74.12% in patients with low expression of CTEN protein, respectively, showing significant differences (χ2=15.727, 15.131, P<0.05). Patients with colorectal cancer of Ⅳ stages didn′t achieve R0 resection and were not involved in tumor-free survival. Results of univariate analysis showed that tumor maximum diameter, histologic grade, TNM stage, tumor with perineural and/or vascular invasion and expression of CTEN protein were associated with the prognosis of patients [HR=4.39, 2.08, 5.73, 3.56, 2.03, 95% confidence interval (CI): 2.49-7.74, 2.21-3.55, 3.29-9.98, 1.82-6.95, 1.18-3.48, P<0.05]. Results of multivariate analysis showed that maximum diameter≥5 cm, Ⅳ stage of TNM stage and high expression CTEN protein were independent risk factors affecting the poor prognosis of patients with colorectal cancer (HR=2.24, 3.57, 2.03, 95 %CI: 1.13-4.20, 1.94-6.59, 1.03-3.98, P<0.05). Conclusions The expression of CTEN protein is up-regelated in colorectal cancer compared with adjacent normal tissues. There is increased expression of CTEN protein in colorectal cancer tissues with maximum diameter of tumor ≥5 cm, high TNM stage and perineural and/or vascular invasion. High expression of CTEN protein is also an independent predicting factor of prognosis. Key words: Colorectal neoplasms; C-terminal tensin-like protein; Prognosis; Immunohistochemical staining
- Research Article
32
- 10.3892/ol.2018.8903
- Jun 5, 2018
- Oncology Letters
The aim of this study was to investigate the expression of FGF2 and FGFR2 in patients with idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) as well as their clinical significance. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to detect FGF2 and FGFR2 expression in LC and adjacent normal tissues of LC patients and lavage fluid of idiopathic pulmonary fibers patients and normal controls (confirmed by bronchoalveolar lavage examination). The expression levels of FGF2 mRNA and protein in the non-small cell LC tissues were significantly higher than those in the adjacent normal tissues (P<0.001). The expression level of FGF2 protein in lavage fluid of patients with IPF was higher than that of the control group (P<0.001). The expression level of FGFR2 mRNA in the non-small cell LC tissues was significantly higher than that in the adjacent normal tissues (P<0.001). The expression level of FGFR2 protein in the non-small cell LC tissues was higher than that in the adjacent normal lung tissues (P<0.001). The expression levels of FGF2 mRNA and FGFR2 mRNA in cancer tissues were not significantly correlated with age, sex and history of smoking (P>0.05), but were significantly correlated with lymph node metastasis, tumor differentiation and TNM staging. FGF2 and FGFR2 proteins were highly expressed in cancer tissues of LC patients and lavage fluid of patients with IPF. The expression of FGF2 mRNA and FGFR2 mRNA was correlated with lymph node metastasis and TNM stage. The high expression levels of FGF2 mRNA and FGFR2 mRNA were associated with tumor metastasis and poor prognosis of LC patients.
- Research Article
35
- 10.1016/j.ajpath.2021.02.020
- Mar 10, 2021
- The American Journal of Pathology
Exploring the Potential of Breast Microbiota as Biomarker for Breast Cancer and Therapeutic Response
- Research Article
11
- 10.3892/ol.2017.5590
- Jan 11, 2017
- Oncology Letters
The endoplasmic reticulum stress inositol-requiring enzyme (IRE) 1α/X-box binding protein (XBP) 1 signaling pathway is involved in the tumorigenesis of breast and prostate cancer. Mucin 2 (MUC2) protects colon tissues from the formation of tumors. In human colorectal cancer (CRC) the role of IRE1α, and its analogue, IRE1β, has yet to be elucidated. In the present study, the expression levels of IRE1α, IRE1β, un-spliced XBP1u, spliced XBP1s and MUC2 in surgically resected cancerous and adjacent non-cancerous tissues from patients with CRC were investigated. The IRE1α, IRE1β, XBP1u, XBP1s and MUC2 mRNA expression levels were determined using reverse transcription-quantitative polymerase chain reaction, and the protein expression levels were detected using immunohistochemistry and western blotting. The association between the expression levels of IRE1α, IRE1β and MUC2 and the clinicopathological features of patients with CRC was subsequently analyzed. The mRNA expression levels of IRE1β and MUC2 were decreased by ~2.1 and ~4.5-fold in CRC tissues, respectively, as compared with the adjacent normal tissues. The protein expression levels of IRE1β and MUC2 were decreased by ~8.0 and ~2.0-fold in the CRC tissues, respectively. IRE1β mRNA expression levels were positively correlated with MUC2 mRNA expression levels. IRE1β expression levels were revealed to be significantly associated with lymph node metastasis, tumor stage and histological differentiation. However, IRE1α, XBP1u and XBP1s mRNA and IRE1α protein expression levels were not observed to significantly differ between cancerous tissues and the adjacent normal tissues. The results indicated that the expression of IRE1β, but not IRE1α, may protect colon tissue from developing CRC by inducing MUC2 expression. Therefore, decreased IRE1β expression levels may be associated with the development of CRC through the inhibition of MUC2 expression.
- Research Article
- 10.1158/1538-7445.am2020-5131
- Aug 13, 2020
- Cancer Research
Purpose: To identify differentially expressed proteins among the esophageal squamous cell carcinoma(ESCC) carcinoma tissue, adjacent normal tissue, normal esophageal mucosa, in order to look out the protein related to different stages and study the molecular mechanism and occurrence of the esophageal squamous cell carcinoma. Methods: Tissue specimens of ESCC and the corresponding clinical data database of ESCC patients were established, a total of 69 patients were selected according to distribution of their sex and age. Two-dimensional gel electrophoresis technology to electrophoresis and get the separation protein of cancerous tissues, adjacent tissues and normal esophageal tissues,then ImageMaster 2D Platinum software was used to search, quantify, match and statistical analysise the proteins on the gel image. 4700 Proteomics Analyzer (TOF/TOFTM) was used to analyze protein spots, in which differentially expressed proteins meet standards were further searched in the Matrix Science, London, UK protein database. Results: Totle 44 and 29 kinds of differentially expressed proteins were screened from esophageal cancer tissues, adjacent noncancerous tissues and normal tissues, among which, there were 13 differentially expressed proteins between esophageal cancer tissues and adjacent noncancerous tissues, 14 differentially expressed proteins between esophageal cancer tissues and normal tissues, 17 between esophageal adjacent noncancerous tissues and normal tissues. These differential expression proteins mainly involved in PKC-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase, nuclear factor of activated T cells(NFAT) pathway, Integrin Signaling Pathway, Cell to Cell Adhesion Signaling, Calmodulin(CaM) nuclear factor of activated T cells, Mineral absorption of calcium binding protein path way(S100), Path way of vascular smooth muscle contraction affe cted by caldesmon, Apoptotic Signaling in Response to DNA Damage path way, which had the function of cytoskeleton structure, protein phosphorylation, acetylation of aminoend, regulation of calcium combination,tumor cell movement, signal transduction, cell differentiation, cell apoptosis, muscle contraction, translation regulation, gene expression, energy metabolism, cell proliferation. Conclusion: This study study achieved differentially expressed protein in ESCC tissue patients, provides new basis for the study of esophageal cancer carcinogenesis mechanism. Citation Format: Fuchun Si. Differentially expressed proteins in esophageal squamous cell carcinoma tissue [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5131.
- Research Article
- 10.21037/tcr-2024-2568
- Jul 14, 2025
- Translational Cancer Research
BackgroundSecreted phosphoprotein 1 (SPP1) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. SPP1 is known to be involved in various cancer-related signaling pathways. Nevertheless, limited research has been conducted on the association between SPP1 and papillary thyroid carcinoma (THCA). This study aimed to investigate the expression of SPP1 in papillary THCA and its relationship with clinical relevance and immune cell infiltration.MethodsThe expression and prognosis of SPP1 in pan-cancer were analyzed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data plat forms. The differential expression of SPP1 between thyroid cancer and adjacent normal tissues was analyzed by the University of Alabama at Birmingham Cancer Data Analysis portal (UALCAN) online database. Thyroid cancer tissues and adjacent tissues were distinguished by the receiver operating characteristic (ROC) curve. The relationship between SPP1 and the signal pathway was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The correlation between SPP1 and immune cell infiltration was analyzed using the Tumor Immune Estimation Resource (TIMER). The correlation between the expression level of SPP1 detected by immunohistochemistry and the clinical characteristics, laboratory parameters, and inflammatory indexes of patients with papillary THCA in our center was verified.ResultsTCGA and GTEx analyses showed that SPP1 was highly expressed in thyroid cancer compared with adjacent tissues, and was related to race, cancer stages, and pathological subtypes. The area under the curve (AUC) of the ROC curve was 0.668 for distinguishing SPP1 expression levels in normal and malignant thyroid tissues. The TIMER database showed that SPP1 expression was positively correlated with B cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells (DC). GO and KEGG pathway analyses showed that SPP1 co-expressed genes were involved in the process of a variety of immune responses and diseases. Immunohistochemical results showed that the positive expression of SPP1 in papillary THCA was higher than that in adjacent tissues and correlated with Tumor-Capsule Distance Status, red blood cell distribution width variation coefficient (RDW-CV), platelet distribution width (PDW), mean platelet volume (MPV), large platelet ratio (P-LCR), mean corpuscular volume (MCV), and mean corpuscular-hemoglobin (MCH), and neutrophil-platelet ratio (NPR).ConclusionsIn papillary THCA, elevated SPP1 expression correlates with clinicopathological features, suggesting its potential as a diagnostic marker.
- Research Article
1
- 10.3760/cma.j.issn.1671-0274.2013.12.019
- Dec 1, 2013
- Chinese Journal of Gastrointestinal Surgery
To investigate the expression of ZBTB8A (zinc finger and BTB domain containing 8A) in gastric cancer tissues and its clinical significance. Level of ZBTB8A mRNA in human normal gastric cell line GES-1, human gastric cancer cell line SGC7901 and MGC803 was detected by real-time PCR. Levels of ZBTB8A mRNA and protein in cancer tissues, adjacent cancer tissues from 104 cases with primary gastric cancer and normal gastric mucosal tissues from 40 cases without malignant gastric diseases were detected by RT-PCR and immunohistochemistry, respectively. Association between ZBTB8A expression and clinicopathology was analyzed. ZBTB8A mRNA expressions in SGC7901, MGC803 and GES-1 cells were 0.00138±0.00015, 0.00158±0.00021, 0.00036±0.000055, respectively, and differences among SGC7901, MGC803 and GES-1 were significant respectively (all P<0.05). ZBTB8A mRNA expression was significantly up-regulated in cancer tissues as compared to adjacent cancer tissues and normal tissues (0.0152±0.0126 vs. 0.0070±0.0061 and 0.0079±0.0036, all P>0.05), while no significant difference was found between adjacent cancer tissues and normal tissues (P>0.05). ZBTB8A expression was significantly associated with invasive depth, lymph node metastasis, tumor stage, and degree of adenocarcinoma differentiation (all P<0.05), but not with age, gender, histological type,gross type (all P>0.05). ZBTB8A may be a potential carcinogenic factor in gastric carcinoma, and may also be involved in gastric adenocarcinoma cell differentiation, cancer invasion and metastasis.
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