scholarly journals S100A4 May Be a Good Prognostic Marker and a Therapeutic Target for Colon Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Sabahattin Destek ◽  
Vahit Onur Gul

Background. Globally, the colorectal cancers rank the third in terms of cancer incidence and rank the fourth in cancer-associated deaths. S100A4, an important member of the S100 protein family, serves to promote tumor progression and metastasis. By conducting this study, we aim to examine the role of S100A4 in the prognosis of colon cancer and to demonstrate its prognostic significance. Methods. Tissue samples of colon cancer from 148 patients who underwent colon resection due to colon cancer were analyzed by immunohistochemical staining to determine the protein expression levels of S100A4. The protein expression levels of S100A4 in tumor tissue were matched with the clinicopathologic factors including patient survival. Results. Cytoplasmic expression of S100A4 protein was demonstrated in the tumor tissue of 132 patients (89.2%) out of a total of 148 study patients. Statistically, the expression levels of the cytoplasmic S100A4 protein correlated significantly with the TNM stages and patient survival. The distribution of the S100A4 protein staining in the tumor tissue was associated with the age groups, tumor localization, TNM staging, and patient survival with statistical significance. The levels of S100A4 protein expression were found to be an independent prognostic factor for TNM staging and poor survival. Conclusion. Expression of the S100A4 protein in colon cancers may be an indicator of tumor progression and lymph node metastasis and may be useful for predicting the overall survival of the patients with colon cancer. In patients with colon cancer, it may be used as an indicator of poor prognosis.

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e62558 ◽  
Author(s):  
Yong Fang ◽  
Jinhuan Wei ◽  
Jiazheng Cao ◽  
Hongwei Zhao ◽  
Bing Liao ◽  
...  

2019 ◽  
Vol 29 (8) ◽  
pp. 1280-1284
Author(s):  
Gui-Ping Yang ◽  
Wei-Peng He ◽  
Jin-Feng Tan ◽  
Zun-Xian Yang ◽  
Rong-Rong Fan ◽  
...  

IntroductionThe solute carrier family 12 member 5 (SLC12A5) gene is playing a putative oncogenic role in colorectal carcinoma. However, the status of SLC12A5 amplification and expression in ovarian carcinoma and its potential clinical and/or prognostic significance has not yet been investigated.MethodsIn the present study, semi-quantitative staining and fluorescence in situ hybridization were used to investigate SLC12A5 protein expression and gene amplification levels. Samples were obtained from archival, formalin-fixed, paraffin-embedded pathological specimens consisting of 30 normal ovaries, 30 ovarian cystadenomas, 30 borderline ovarian tumors, and 147 invasive ovarian carcinomas. SLC12A5 immunohistochemical staining results, pathological parameters, and patient prognosis were then evaluated using various statistical models. Patient survival rate was also assessed using receiver-operator curve analysis.ResultsOur results revealed no SLC12A5 protein overexpression in normal ovaries. However, 7% of cystadenomas had SLC12A5 protein overexpression along with 17% of borderline tumors and 37% of ovarian carcinomas (P<0.01). Amplification of SLC12A5 was detected in 10.3% of ovarian carcinomas. Further correlational analyses showed that SLC12A5 protein overexpression in ovarian carcinomas was significantly associated with ascending histological grade, pT/pN/pM status, as well as FIGO stage (P<0.05). A subsequent univariate survival analysis of our ovarian carcinoma cohorts resulted in a significant association between SLC12A5 protein overexpression and decreased patient survival (44.3 and 85.9 months for high and low SLC12A5 protein expression, respectively; P<0.001). Importantly, additional multivariate analysis revealed that SLC12A5 protein expression was a significant, independent prognostic factor for overall survival in ovarian carcinoma patients (P=0.003).ConclusionsCollectively, these findings support the conclusion that SLC12A5 protein overexpression could indicate an invasive and/or aggressive phenotype of ovarian carcinoma. Future work will need to investigate whether SLC12A5 protein can serve as an independent prognostic molecular marker in patients with ovarian carcinoma.


2010 ◽  
Vol 29 (1) ◽  
pp. 71 ◽  
Author(s):  
Jian-fang Liang ◽  
Hong-kun Wang ◽  
Hong Xiao ◽  
Ning Li ◽  
Cai-xia Cheng ◽  
...  

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 625-625
Author(s):  
Antonia K. Roseweir ◽  
James Hugh Park ◽  
Sanne ten Hoorn ◽  
Arfon GMT Powell ◽  
Campbell SD Roxburgh ◽  
...  

625 Background: There has been enormous effort to develop a prognostic genomic classification of colorectal cancer (CRC). As a result, mismatch repair (MMR) status was established as a prognostic marker in addition to TNM-staging. Phenotypic subtypes were recently proposed that stratified patient survival, however their clinical utility had not been compared to other proposed classification systems including consensus molecular subtypes (CMS) or current prognostic markers including MMR status. Methods: Three patient cohorts, a pilot cohort of 237 stage I-III CRC patients, a validation cohort of 879 stage I-III CRC patients, and the AMC-AJCCII-90 cohort with 81 stage II colon cancer patients were utilised to investigate associations between phenotypic subtypes, MMR status, CMS and patient survival. Results: In the pilot cohort, phenotypic subtype stratified cancer-specific survival (P < 0.001). In the validation cohort, phenotypic subtype stratified overall (p = 0.003) and cancer-specific survival (CSS, p < 0.001) independent of tumour location. MMR status associated with right-sided colon cancer (p < 0.001), therefore further analysis was restricted to this subset of patient (n = 380). The immune subtype had the highest MMR deficiency (p = 0.001). Phenotypic subtype (p < 0.001) more effectively stratified CSS than MMR status (p = 0.023). Furthermore, in left-sided colon cancer (p = 0.007) and rectal cancer (p < 0.001) only phenotypic subtype stratified CSS. Phenotypic subtype and not MMR status was independently prognostic in the full cohort (p < 0.001) and right-sided colon cancer (p < 0.001). In the AMC-AJCCII-90 cohort phenotypic subtypes aligned with CMS (p < 0.001) and stratified overall survival better than CMS (p = 0.125 v p = 0.487 respectively). Conclusions: Phenotypic subtype is a more effective prognostic classification than CMS and MMR status. Phenotypic subtypes should be incorporated alongside MMR status as a clinical aid for the prognosis of patients with CRC.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5404-5404 ◽  
Author(s):  
Le Zhang ◽  
Bing Xia ◽  
Shanqi Guo ◽  
Xiaowu Li ◽  
Fulian Qu ◽  
...  

Abstract MYC protein expression has been identified to be associated with inferior overall survival (OS) and progression-free survival (PFS) when coexpressed with BCL-2 protein in patients with diffuse large B cell lymphoma (DLBCL). But the concurrent expression of MYC and BCL-2 proteins in primary gastrointestinal (PGI)-DLBCL has not been clearly understood. Here, we investigated whether this coexpression has prognostic significance in PGI-DLBCL patients and explored its associations with patients’ clinical parameters. We enrolled 60 PGI-DLBCL patients and 30 age- and sex-matched healthy controls. Expression levels of MYC and BCL-2 were detected from both protein and mRNA levels by immunohistochemistry and real-time RT-PCR. Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein were correlated with high MYC and BCL-2 mRNA expression, respectively (both p<0.05). We found that patients with advanced-stage disease (at IIE-IV) having higher MYC and BCL-2 coexpression levels (p<0.05). In addition, MYC+/BCL-2+ patients had more difficulty achieving complete remission than others (p<0.05). Presence of MYC protein expression only affected OS and PFS when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (p<0.05) even after adjusting for age, Lugano stage, IPI, and BCL-2 protein expression in a multivariable model. MYC+/BCL-2+ patients have poorer chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting prognosis of PGI-DLBCL patients. Disclosures No relevant conflicts of interest to declare.


2005 ◽  
Vol 23 (10) ◽  
pp. 2318-2324 ◽  
Author(s):  
Maija R.J. Kohonen-Corish ◽  
Joseph J. Daniel ◽  
Charles Chan ◽  
Betty P.C. Lin ◽  
Sun Young Kwun ◽  
...  

Purpose The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O6-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer. Patients and Methods The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT, and mismatch repair protein expression, as well as MGMT and p16 promoter hypermethylation. Results We showed that MSI-L defines a group of patients with poorer survival (P = .026) than MSS patients, and that MSI-L was an independent prognostic indicator (P = .005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival. Conclusion MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Huang ◽  
Guihua Wang ◽  
Chunmei Zhao ◽  
Rong Geng ◽  
Shu Zhang ◽  
...  

Colorectal cancer (CRC) is a complex and heterogeneous disease with four consensus molecular subtypes (CMS1-4). LTBP2 is a member of the fibrillin/LTBP super family and plays a critical role in tumorigenesis by activating TGF-β in the CMS4 CRC subtype. So far, the expression and prognostic significance of LTBP2 in CRC remains obscure. In this study, we aimed to analyze the mRNA and protein expression levels of LTBP2 in CRC tissues and then estimate their values as a potential prognostic biomarker. We detected the mRNA expression of LTBP2 in 28 cases of fresh CRC tissues and 4 CRC cell lines and the protein expression of LTBP2 in 483 samples of CRC tissues, matched tumor-adjacent tissues, and benign colorectal diseases. LTBP2 protein expression was then correlated to patients’ clinical features and overall survival. Both LTBP2 mRNA and protein expression levels in CRC tissues were remarkably superior to those in adjacent normal colorectal tissues (P=0.0071 and P<0.001, respectively), according to TCGA dataset of CRC. High LTBP2 protein expression was correlated with TNM stage (P<0.001), T stage (P<0.001), N stage (P<0.001), and M stage (P<0.001). High LTBP2 protein expression was related to poor overall survival in CRC patients and was an independent prognostic factor for CRC. LTBP2 mRNA expression was especially higher in the CMS4 subtype (P<0.001), which was confirmed in CRC cell lines. Our data suggested that LTBP2 may act as an oncogene in the development of colorectal cancer and have important significance in predicting CRC prognosis. LTBP2 could be a novel biomarker and potential therapeutic target for mesenchymal colorectal cancer and can improve the outcome of high-risk CRC.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yun Liu ◽  
Yong Yang ◽  
Linna Jiang ◽  
Hongrui Xu ◽  
Junwei Wei

Solute Carrier Family 38 Member 1 (SLC38A1) is a principal transporter of glutamine and plays a crucial role in the transformation of neoplastic cells. However, the correlation between SLC38A1 expression, prognosis, and immune infiltration in hepatocellular carcinoma (HCC) has yet to be elucidated. We used two independent patient cohorts, namely, a Cancer Genome Atlas (TCGA) cohort and a Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort, to analyze the role of SLC38A1 in HCC at the mRNA and protein levels, respectively. In these two cohorts, SLC38A1 mRNA and protein expression levels were higher in HCC tissues than in adjacent nontumor tissues. Both SLC38A1 mRNA and protein expression were positively associated with clinicopathological characteristics (clinical stage, T stage, pathological grade, tumor size, and tumor thrombus), were negatively associated with survival, and were independent prognostic factors in HCC patients. Functional enrichment analyses further indicated that SLC38A1 was involved in multiple pathways related to amino acid metabolism, tumors, and immunity. High expression levels of SLC38A1 were inversely proportional to CD8+ T cells and directly proportional to macrophages M0, neutrophils, programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Moreover, we used immunohistochemical analysis of tissue samples and other online databases to further validate the expression levels and prognostic significance of SLC38A1 in HCC. Collectively, our study demonstrated that the upregulated expression of SLC38A1 was related to an unfavorable prognosis and defective immune infiltration in HCC.


2015 ◽  
Author(s):  
Byung Woog Kang ◽  
Jong Gwang Kim ◽  
Yee Soo Chae ◽  
Soo Jung Lee ◽  
Shinkyo Yoon ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17028-e17028
Author(s):  
E. Pectasides ◽  
G. Founztilas ◽  
C. Sasaki ◽  
B. Burtness ◽  
A. Psyrri

e17028 Background: Deregulated signaling through phosphatidylinositol 3’-kinase (PI3K) pathway is common in several cancers, including HNSCC. In the present study we investigated the relationship between PI3K protein expression and outcome in patients with HNSCC. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for PI3K were analyzed using an immunofluorescence-based assay that provides an automated, quantitative analysis of expression within subcellular compartments (AQUA). Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance. Results: Mean follow-up time for the cohort was 40 months. Ninety-seven of 122 cases had sufficient tissue for analysis and continuous AQUA scores were divided into quartiles. Survival analysis showed that patients in the top and bottom quartile had a significantly shorter OS (p = 0.015). In multivariable analysis, adjusting for well-characterized prognostic variables, PI3K expression retained its prognostic significance. Conclusions: Our study suggests that in situ quantitative measurement of PI3K stratifies HNSCC into four expression levels where both low and high levels are associated with a worse outcome. We speculate that transmission of growth factor receptor signals that promote tumor aggression in these low expressers may occur via PI3K/Akt independent mechanisms. It is possible that activation of such alternate pathways in some tumors results in the down-regulation of PI3K expression via a feedback mechanism, producing aggressive tumors bearing a PI3K-low phenotype. No significant financial relationships to disclose.


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