scholarly journals Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity within tumor-related genes in colorectal cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xueyun Huo ◽  
Dandan Feng ◽  
Shuangyue Zhang ◽  
Zhenkun Li ◽  
Xiaohong Li ◽  
...  

Abstract Background Microsatellite instability (MSI) is a biomarker for better outcomes in colorectal cancer (CRC). However, this conclusion is controversial. In addition, MSs can be a useful marker for loss of heterozygosity (LOH) of genes, but this finding has not been well studied. Here, we aimed to clarify the predictive value of MSI/LOH within tumor-related genes in CRC. Methods We detected MSI/LOH of MSs in tumor-related genes and the Bethesda (B5) panel by STR scanning and cloning/sequencing. We further analyzed the relationship between MSI/LOH status and clinical features or outcomes by Pearson’s Chi-square test, Fisher’s exact test and the Kaplan–Meier method. Results The findings indicated that the MSI rates of B5 loci were all higher than those of loci in tumor-related genes. Interestingly, MSI/LOH of 2 loci in the B5 panel and 12 loci in tumor-related genes were associated with poorer outcomes, while MSI/LOH of the B5 panel failed to predict outcomes in CRC. MSI of BAT25, MSI/LOH of BAT26 and MSI of the B5 panel showed closer relationships with mucinous carcinoma. In addition, LOH-H of the B5 panel was associated with increased lymphatic metastasis. Conclusions In summary, MSI/LOH of certain loci or the whole panel of B5 is related to clinical features, and several loci within tumor-related genes showed prognostic value in the outcomes of CRC.

2019 ◽  
Author(s):  
Xueyun Huo ◽  
Dandan Feng ◽  
Shuangyue Zhang ◽  
Zhenkun Li ◽  
Xiaohong Li ◽  
...  

Abstract Background: Microsatellite instability (MSI) has been known as a biomarker for better outcome in colorectal cancer (CRC). However, the conclusion is controversy. In addition, MS can also be a useful marker for loss of heterozygosity (LOH) of genes but it has not been well studied yet. Here, aimed to clarify the predictive value of MSI/LOH within tumor-related genes in CRCs, we detected MSI/LOH of MSs in tumor-related genes and the Bethesda (B5) panel and further analyzed the relationship between MSI/LOH and clinical features or outcomes. Results: As expected, the MSI rate of B5 loci were all very high, suggesting that B5 panel criterion is powerful for MSI status determining of CRCs. Interestingly, MSI/LOH of 2 loci in the B5 panel and 12 loci in tumor-related genes were associated with poorer outcome while MSI/LOH of B5 panel was failed to predict outcomes of CRCs. MSI of BAT25, MSI/LOH of BAT26 and MSI of B5 panel showed closer relationship with mucinous carcinoma. In addition, LOH-H of B5 panel associated with more lymphatic metastasis. Conclusions: In summary, MSI/LOH of certain loci or whole panel of B5 were related to the clinical features, and several loci within tumor-related genes showed a prognostic value in outcomes of CRCs.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yue Zhong ◽  
Zhenjie Zhuang ◽  
PeiJu Mo ◽  
Qi Shang ◽  
Mandi Lin ◽  
...  

Background. Myelin and lymphocyte, T cell differentiation protein 2 (MAL2) is highly expressed in various cancers and associated with the development and prognosis of cancer. However, the relationship between MAL2 and breast cancer requires further investigation. This study aimed to explore the prognostic significance of MAL2 in breast cancer. Methods. MAL2 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas (TCGA) database and verified by quantitative real-time polymerase chain reaction (RT-qPCR). The chi-square test or Fisher’s exact test was used to explore the association between clinical characteristics and MAL2 expression. The prognostic value of MAL2 in breast cancer was assessed by the Kaplan–Meier method and Cox regression analysis. Gene set enrichment analysis (GSEA) was performed to identify the biological pathways correlated with MAL2 expression in breast cancer. Besides, a single-sample GSEA (ssGSEA) was used to assess the relationship between the level of immune infiltration and MAL2 in breast cancer. Results. Both bioinformatics and RT-qPCR results showed that MAL2 was expressed at high levels in breast cancer tissues compared with the adjacent tissues. The chi-square test or Fisher’s exact test indicated that MAL2 expression was related to stage, M classification, and vital status. Kaplan–Meier curves implicated that high MAL2 expression was significantly associated with the poor prognosis. Cox regression models showed that high MAL2 expression could be an independent risk factor for breast cancer. GSEA showed that 14 signaling pathways were enriched in the high-MAL2-expression group. Besides, the MAL2 expression level negatively correlated with infiltrating levels of eosinophils and plasmacytoid dendritic cells in breast cancer. Conclusion. Overexpression of MAL2 correlates with poor prognosis and lower immune infiltrating levels of eosinophils and plasmacytoid dendritic cells in breast cancer and may become a biomarker for breast cancer prognosis.


2020 ◽  
Vol 2 (2) ◽  
pp. 107-117
Author(s):  
Mariana Pereira ◽  
Ana Pereira ◽  
Patrícia Silva ◽  
Catarina Costa ◽  
Sandra F. Martins

Background: Colorectal cancer (CRC) surgery is associated with high rates of postoperative morbimortality. Sarcopenia has been identified as an independent predictor of these surgical outcomes. Methods: A sample of 272 patients who underwent CRC surgery between January 2005 and May 2010 at Braga Hospital, was selected. Sarcopenia was defined by the skeletal muscle mass index, measured by preoperative computed tomography (CT), at L3 level, using ImageJ® software. Associations between sarcopenia and qualitative variables were analyzed by Chi-Square Test (χ2) or Fisher’s Exact Test and, for quantitative variables, by Mann-Whitney Test. A multivariate logistic regression was performed to assess if sarcopenia was an independent predictor of major morbidity. The overall and recurrence-free survivals were analyzed by Kaplan-Meier method and multivariate Cox regression was performed for recurrence-free survival. Results: The prevalence of sarcopenia was 19.1%. Sarcopenia was associated with male gender, no CRC family history and colon tumour (p < 0.001, p = 0.029 and p = 0.017, respectively). The presence of sarcopenia was associated with postoperative morbidity Clavien–Dindo classification (p = 0.003), and sarcopenia was an independent predictor for major complications (grade ≥ III) (p = 0.003). Conclusions: The evaluation of sarcopenia in patients undergoing CRC surgical resection allows to predict a higher probability of major postoperative morbimortality.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 489-489
Author(s):  
Elie W. Akl ◽  
Pier Vitale Nuzzo ◽  
Elio Adib ◽  
Amin Nassar ◽  
Sarah Abou Alaiwi ◽  
...  

489 Background: Immune checkpoint inhibition (ICI) has greatly improved clinical outcomes for pts with mUC and other cancers. ICI is associated with a class of AEs, deemed irAEs due to immune activation. Nonetheless, biomarkers associated with irAE are still lacking. We hypothesized that the immune response against neoantigens is partly responsible for irAEs and investigated the association between irAEs, TMB and response to ICI. Methods: We identified patients with mUC at Dana Farber Cancer Institute who were treated with ICI (monotherapy or combination) and had available tumor sequencing data through Oncopanel. TMB was calculated using the number of non-synonymous exonic mutations per megabase. The severity of irAEs was graded using CTCAE v.5.0. Mann-Whitney U test was performed to identify association between TMB, incidence and grade of irAEs. A cut-off of 10/mb was assigned for TMB. Fisher’s exact test was used to evaluate the radiologic response between pts with and without irAEs and low vs. high TMB. Multivariable linear regression was used to assess the relationship between TMB, irAEs and response. p-values were adjusted using Benjamini-Hochberg method. Results: Of 101 pts with mUC who met the inclusion criteria, 32 (32%) reported irAEs. 6 (6%) were grade (G)1, 20 (20%) were G2, and 6 (6%) were G3. Median(m) time on therapy was 84 days for pts without irAEs and 88 days for pts with irAEs. Pts with irAEs had higher mTMB (15.4/mb) compared to pts with no irAEs (9.8) ( p = 0.01). In pts on monotherapy (93), those with irAEs (n=27) had a higher mTMB (15.13/mb) compared to pts with no irAEs (n=66) (mTMB = 10.20/mb) ( p = 0.01). Out of 94 pts with radiological data, response was achieved in 16 (50%) pts with irAE vs 10 (16%) pts with no irAE ( p < 0.001). When both irAE and response were included in a multivariable regression, the association between irAE and TMB was not significant ( p = 0.4). Pts with both irAE and high TMB had a response rate of 56% which was significantly higher than those with either irAE but low TMB (28.6%) or high TMB but no irAE (21.2 %) or low TMB and no irAE (10.3%) (Chi-square test p = 0.002; FDR corrected p-values for individual comparisons in Table). There was no association between TMB and irAE grade. Conclusions: Higher TMB was associated with higher incidence of irAEs in pts with mUC on ICIs. Moreover, pts with both high TMB and irAEs exhibited better response rates than those with only high TMB or irAEs, suggesting that they may provide complementary tumor and host characteristics. Further evaluation in mUC is needed to confirm this relationship between TMB, irAEs and response in a larger cohort and explore specific mutational signatures that may be associated with irAEs. [Table: see text]


2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.


2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.


2019 ◽  
Vol 160 (38) ◽  
pp. 1503-1509
Author(s):  
Réka Szabó ◽  
Gergely Farkas ◽  
Mária Keszeg ◽  
Gabriella Eördegh ◽  
Norbert Buzás ◽  
...  

Abstract: Introduction: The compromise effect is a well-known phenomenon in the world of marketing, but it is rarely examined in medical settings. In dental setting, the patient often has to make treatment-related decisions with price as the only available and comprehensible information to help informed choice. Aim: We sought to determine if the compromise effect plays a role in dental treatment choices, and if yes, how the effect is modified by factors such as perceived quality, professional jargon in the explanations, or the importance of keeping one’s own teeth intact. Method: 676 volunteers participated in this questionnaire-based study. The questionnaires were filled in anonymously. Altogether 8 versions of the same questionnaire were generated, in which the following information was given in varying combinations: the names of five different dental treatments from cheap to expensive, their possible prices, and additional information about the treatment. Statistical analysis: The significance of the relationship between the relative frequency of responses and the available additional information was determined by chi-square test and Fisher’s exact test. Results: The respondents did not approach dental treatment-related decisions on a heuristic basis by default, most probably because of their preconceptions and previous experiences in connection with dental treatments. Esthetics turned out to be of utmost importance and expectable lifespan was also information that significantly influenced the choices. Conclusion: Extra information can and does influence informed dental treatment choice on the patient side, provided it is offered in a clear, proper, and intelligible form, which points out the importance of professional communication. Orv Hetil. 2019; 160(38): 1503–1509.


2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Junjie Jiang ◽  
Hui-Ju Wang ◽  
Xiao-Zhou Mou ◽  
Huanqing Zhang ◽  
YiZhen Chen ◽  
...  

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC. Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly. Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues. Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.


e-NERS ◽  
2013 ◽  
Vol 1 (1) ◽  
Author(s):  
Martha Revy Sarame ◽  
A. Y. Ismanto ◽  
Abram Babakal

Abstract: Immunization is the vaccine into the body in the form of weakened germs that cause the body to produce antibodies but not cause disease, even children become immune.  The research objective was to determine the relationship of maternal knowledge about immunization with complete basic immunization in infants at IHC Health Center Village Paniki working area Ondong Tagulandang Biaro Siau Islands District . The study design was cross sectional method and using Chi-Square test on the value of the Fisher Exact Test. The study was conducted on 32 mothers of infants aged 9-12 months. Sampling with a total sampling instrument in the form of a questionnaire study to determine the motherʾs knowledge and KMS (Card Towards Health) to determine the completeness of immunization. The analysis shows there is a significant relationship between maternal knowledge about immunization with complete basic immunization in infants (p = 0,000). Conclusion that mothers with a good knowledge of immunization will do complete basic immunization in children compared to mothers with less knowledge about immunization. Keywords: Knowledge mother, Completed Basic Immunization.   Abstrak: Imunisasi  adalah pemberian vaksin ke dalam tubuh berupa bibit penykit  yang  dilemahkan yang menyebabkan tubuh memproduksi antibodi tetapi tidak menimbulkan penyakit, bahkan anak menjadi kebal. Tujuan penelitian adalah untuk mengetahui  hubungan pengetahuan ibu tentang imunisasi dengan kelengkapan pemberian imunisasi dasar pada bayi di Posyandu Kelurahan Paniki wilayah kerja Puskesmas Ondong Kabupaten Kepulauan Siau Tagulandang Biaro. Desain penelitian ini menggunakan metode Cross Sectional dan menggunakan  uji Chi-Square pada nilai Fisher Exact Test. Penelitian dilakukan pada 32 ibu yang memiliki bayi berusia 9-12 bulan. Pengambilan sampel secara total sampling dengan instrument penelitian berupa kuesioner untuk mengetahui pengetahuan ibu dan KMS (Kartu Menuju Sehat) untuk mengetahui kelengkapan imunisasi. Hasil analisis menunjukkan  terdapat hubungan bermakna antara pengetahuan ibu tentang imunisasi dengan kelengkapan pemberian imunisasi dasar pada bayi (p=0.000). Kesimpulan yaitu ibu dengan pengetahuan tentang imunisasi yang baik akan melakukan pemberian imunisasi dasar lengkap pada anaknya dibandingkan ibu dengan  pengetahuan tentang imunisasi yang kurang. Kata kunci: Pengetahuan ibu, Kelengkapan Imunisasi Dasar.


2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  

Abstract Background The study was designed to examine the reversion inducing cysteine rich protein with Kazal motifs (RECK) levels in patients with cholangiocarcinoma (CCA) and assess its role in CCA prognosis. Methods Quantitative real-time PCR (qRT-PCR) was used to determine the expression of RECK mRNA in 127 pairs of CCA samples and controls. Chi-square test was conducted to analyze the effects of clinical features on RECK expression. Kaplan-Meier curves were plotted to determine the overall survival rate of CCA patients with different RECK expression. The prognostic biomarkers for CCA patients were identified using the Cox regression analysis. Results Significantly down-regulated expression of RECK mRNA was determined in CCA tissues compared to noncancerous controls (P < 0.05). Chi-square test suggested reduced RECK expression was related with invasion depth (P = 0.026), differentiation (P = 0.025), lymphatic metastasis (P = 0.010) and TNM stage (P = 0.015). However, age, sex, tumor size and family history had no significant links with RECK expression (all, P > 0.05). The survival curves showed that patients with low RECK expression had a shorter overall survival rate than those with high RECK expression. Both the univariate analysis (P = 0.000, HR = 5.290, 95%CI = 3.195–8.758) and multivariate analysis (P = 0.000, HR = 5.376, 95%CI = 2.231–8.946) demonstrated that RECK was an independent biomarker for predicting the outcomes of CCA patients. Conclusions Taken together, the expression of RECK was down-regulated in CCA and it might be an efficient biomarker for CCA patients.


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