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DCC is methylated. 130 / 130
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"While the sensitivity and specificity of DCC methylation analysis were 76.0% (95%CI: 61.8–86.9) and 72.4% (95%CI: 59.1–83.3)."

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"The CGI spanning promoter/exon 1 of DCC was methylated at Taq I site in 8 out of 10 tumors as demonstrated by almost complete digestion with Taq I whereas it was methylated in matching normal colon tissues only in sample #8 and #10 ( xref ."

sparser
"Taylor et al. found methylation in DCC in 9 of 10 cases of precursor B ALL and in RUNDC3B , KCNK2 , and DLC1 in 7, 7 and 8 (respectively) of these 10 cases [ xref ]."

sparser
"DCC gene methylation was significantly different between plasma from controls, GGO, and lung cancer patients 4/80 (5%), 0/23 (0%) and 19/70 (26%), respectively (p=0.0002)."

sparser
"The methylation of Kif1a, DCC, RarB, and NISCH were examined in these groups ( xref )."

sparser
"Next, we investigated the association between DCC promoter methylation and various clinicopathological and genetic features."

sparser
"DNA methylation of DCC , EDNRB , DAPK , CCNA1 , p16 , HOXA9 and KIF1A genes have been detected in primary tissues and biological fluids, including saliva and plasma [ xref , xref , xref , xref ], derived from HNSCC patients."

sparser
"While EDNRB methylation density rose from 0.3% pretreatment to 1.1% on Day 391, DCC methylation density rose from 1.4% before surgery to 1.5% on Day 391."

sparser
"SSTR1 methylation was significantly correlated with tumor size, stage, and methylation of galanin , GALR2 , TAC1 , TAC1R , H-cadherin , MGMT , DAPK , and DCC methylation [ xref ]."

sparser
"The evaluation of the markers in the study cohort confirmed that PAX5 , EDNRB , and DCC were frequently methylated among patients with HNSCC."

sparser
"DCC methylation status was significantly associated with MSI status."

sparser
"MSI-positive gastric cancers were significantly more frequently associated with DCC methylation than with DCC unmethylation (23 vs. 6 %, P  = 0.013; Table  xref )."

sparser
"We assessed CCNA1, DCC, MGMT, CDKN2A/p16, and DAPK methylation status in HNSCC cell lines and their association with anti-EGFR treatment response."

sparser
"Furthermore, when only the healthy controls registered in this study were examined, no significant differences were found in the values of salivary DCC methylation with respect to sex ( p  = 0.12), history of drinking ( p  = 0.22), smoking ( p  = 0.59), or BMI ( p  = 0.436) (Supplementary Fig.  xref )."

sparser
"A comparison of the DCC methylation values in cancer tissue and saliva samples from each case of the derivation cohort is shown in Supplementary Fig.  xref ."

sparser
"Similarly, another study showed that aberrant methylation of the EDNRB, KIF1A and DCC genes is common in oral cancer patients."

sparser
"Furthermore, it is noteworthy that in most cases, including those with no recurrence to date, the DCC methylation cutoff value set in this study was exceeded after treatment."

sparser
"Methylation of CCNA1 , NDN , CD1A , and DCC was higher, while methylation of p16 was lower, in HPV (+) tumors compared to HPV (-) tumors."

sparser
"In addition, although there were some cases in which saliva samples were hypermethylated despite low DCC methylation in carcinoma tissues and vice versa, DCC methylation in saliva was detectable in almost all cancer cases."

sparser
"A significant reduction in the DCC methylation pattern was observed in the valproic group (p = 0.023)."

sparser
"DNA methylation of PTPN6, MOS, DCC, CRK, and VAV1 was evaluated in non-neoplastic gastric specimens using quantitative methylation-specific PCR in patients with GC (n = 207) and their age- and gender-matched controls (n = 207)."

sparser
"However, multivariate logistic regression analysis showed that, the DCC methylation cut-off value set in this study was not significantly affected by patient background factors, including smoking and obesity."

sparser
"DCC methylation was lower in the valproic acid group than in the placebo group."

sparser
"In addition, no significant differences in DCC promoter methylation due to sex or lifestyle habits were observed in healthy controls."

sparser
"DCC is a tumour suppressor and both deletion and promoter methylation of DCC are involved in its frequent downregulation in colorectal cancer ( xref ; xref )."

sparser
"This analysis showed that TGFβR2, CALCA , HIC1 , SOCS1, RARβ, COX2 , CDH1 , THBS1 , HIN1 , CDKN2B , UCHL1 , CCND2 , MT1G and DCC were frequently methylated in control samples, showing low specificity (Table  xref )."

sparser
"Mydlarz et al. detected EDNRB , p16 and DCC methylation by analyzing serum DNA from HNSCC patients and revealed that serum EDNRB hypermethylation was highly specific for HNSCC but it was not sensitive [ xref ]."

sparser
"Therefore, we conclude that aberrant methylation of DCC in the saliva of patients with superficial hypopharyngeal cancer is a reliable, disease-specific factor."

sparser
"There were no significant differences in overall methylation of CCNA1, DCC, CD1A or NDN within paired specimens ( p -values= 0.56, 0.17, 0.66 and 0.58, respectively)."

sparser
"Recently, two reports indicated that UNC5C and DCC methylation was closely associated with loss of gene expression in colorectal cancer."

sparser
"Shin et al. reported the promoter methylation of MOS, DCC, CRK , and PTPN6 in gastric cancer [ xref ]."

sparser
"Third, although a downward trend in the DCC methylation value was confirmed after treatment, our study has not yet demonstrated its utility in disease monitoring using saliva samples."

sparser
"However, the DCC methylation values after treatment were above the set cutoff in the majority of patients in both the non-recurrence and recurrence groups."

sparser
"In OSCC, different levels of methylation have been reported for the p16 , p15 , p14 , DCC , DAPK , MINT1 , MINT2 , MINT27 , and MINT31 gene promoters and DCC methylation was associated with bone invasion of gingival tumors, invasiveness, and reduced survival (Ogi et al. xref )."

sparser
"In the salivary rinse samples collected with brush, smoking status was associated with promoter methylation of TIMP3 ; HPV status was associated with promoter methylation of CCNA1 , DCC , and MGMT ; primary tumor site (Oral cavity) was associated with promoter methylation of CCNA1 , DCC and DAPK ; clinical TNM stage were associated with promoter methylation of P16 , DCC , and MINT31 ; and pathological nodal stage was associated with promoter methylation of P16 and MINT31 ( xref )."

sparser
"To our knowledge, this report is the first study analyzing ROBO1 and DCC methylation in NB."

sparser
"In other tumor types such as gastric [31] and breast [32] cancer, oral squamous cell carcinoma [33] and acute lymphoblastic leukemia [34] , abnormal DCC methylation has been described."

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"Determination of Aberrant Promoter Methylation of DCC."
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sparser
"Aberrant promoter methylation of DCC as determined by quantitative methylation-specific PCR showed significant differences in DCC promoter methylation status of patients with lung cancer and controls ( P = ."
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sparser
"In addition, positive correlation with TIMP3 and a marginal correlation with DCC methylation were observed."

sparser
"The methylation of DCC in fcDNA was associated with age (r s =0.254; P = ."
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"Deleted in colorectal cancer was validated as a tumor marker in head and neck cancer xref as well as esophageal SCC. xref Deleted in colorectal cancer is present on chromosome 18q, suppresses epithelial cell malignant phenotype, xref and is involved in apoptosis. xref It appeared to be a highly specific assay as remarkably aberrant methylation of DCC promoter was not observed in any of the control plasma samples, with AUC ROC curve to be 0.76 (95% CI: 0.641-0.88, P < ."
| PMC

sparser
"DCC methylation was detected in 16/47 (34%) HIV-NHL, and was more frequent in HIV-DLBCL (12/28; 43%) compared to HIV-BL (3/11; 27%), and HIV-PEL (1/8; 13%)."

sparser
"Recently, we examined the methylation status of the DCC gene in colorectal carcinomas and found that aberrant methylation of the DCC gene was detected in 28 out of the 50 (56%) primary colon carcinomas."

sparser
"Aberrant methylation of the DCC gene was detected in 16 out of the 36 (44%) primary gastric carcinomas."

sparser
"DCC methylation was observed in the course of gastric carcinogenesis and disappeared in advanced gastric carcinoma."

sparser
"Methylation of DCC was correlated with aggressive phenotype for HNC in a study of 96 tumors with increased rate of bone invasion, invasive growth pattern and reduced survival (p=0.050). ( xref ) Intriguingly, in this study, methylation of p14ARF was associated with a good prognosis (HR =0.30 for methylated tumors p=0.021), perhaps implicating a mechanism similar to the protective effect of p16 methylation in our cohort."

sparser
"Tobacco use was significantly associated with methylation of NDN , CD1A , and DCC ( p-value  = 0.02; p-value  < 0.001; p-value  = 0.03, respectively)."

sparser
"ESR1 and DCC methylation were significantly higher in HPV16-positive women."

sparser
"EDNRB was methylated in 67 of 92 (72.8%) tumors, KIF1A was methylated in 66 of 92 (71.7%) tumors, p16 was methylated in 44 of 92 (47.8%) tumors and DCC was methylated in 54 of 92 (58.7%) tumors."

sparser
"Further, when different combinations of genes were evaluated, OSCC harboring both p16 and DCC methylation emerged to be more significantly associated with nodal involvement than p16 alone ( p = 0.005, OR = 19.2, 95% C.I. =2.4–152.8; xref )."

sparser
"Interestingly, only subjects with an abnormal cytology had high (>16%) mean levels of DCC methylation across the five sites analyzed ( xref ), although this was true only for six of those with abnormal cytology (range: 17.0–70.2%), all HPV 16 positive."

sparser
"Of these six subjects with high average DCC methylation, 1 had atypical squamous cells of undetermined significance, 2 had low grade squamous intraepithelial lesions, 2 had high grade squamous intraepithelial lesions and 1 had atypical glandular cells cytology."

sparser
"However, CD1A and DCC methylation had lower probabilities indicating that in the tumor microenvironment, some genes are stably methylated while others are not, presumably to promote the tumorigenic phenotype."

sparser
"Ogi et al . xref showed promoter methylation of DCC gene in 16 of 96 primary OSCC."

sparser
"DCC methylation was correlated with bone invasion, and deep invasion of the tongue."

sparser
"Finally, methylation of NDN and DCC was significantly higher in males compared to females ( p-value =0.003; p-value =0.002, respectively)."

sparser
"Primary oral cancer patients with methylated DCC had a significantly reduced survival than those who did not have DCC methylation. xref The presence ofp16 INK4a or DCC methylation in the primary tumor has been shown to be associated with poor outcome. xref , xref , xref Our study supports these findings."

sparser
"Schussel et al. [40] demonstrated that HOXA9 , EDNRB , and DCC methylation was associated with premalignant or malignant disease in saliva of a high-risk population, comparing well with examinations o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Although the presence of DCC methylation alone was not a predictor of nodal involvement, combination withp16 INK4a emerged to be more significantly associated thanp16 INK4a alone."

sparser
"The impact ofp16 INK4a and DCC methylation in the primary tumor on nodal involvement was not related to histology or the tumor size."

sparser
"Overall, 70 % (58 of 83 informative cases) and 51 % (40 of 79 informative cases) of gastric cancers harbored either LOH or aberrant methylation in the DCC and UNC5C genes, respectively."

sparser
"DCC methylation has been identified as biologically important in head and neck squamous cell carcinoma (HNSCC) ( xref )."

sparser
"Patients with exfoliated tumors cells positive for DCC methylation showed a trend toward a lower local recurrence-free survival."

sparser
"We report CCNA1 and DCC methylation levels similar to previous studies( xref – xref )."

sparser
"DCC methylation was highly variable, and there were six subjects with notably high mean levels of DCC methylation and corresponding abnormal cytology (of which 1 was atypical squamous cells of undetermined significance, 2 were low grade squamous intraepithelial lesions, 2 were high grade squamous intraepithelial lesions and 1 was atypical glandular cells), indicating that DCC may be another promising marker of abnormal cytology."

sparser
"Several loci , including RASSF1 , PITX2, CDH13 , HS3ST2 , TWIST1, TAL1 , TUSC3, and DCC were more frequently methylated in sporadic VHL wild-type ccRCC than in familial ccRCCs."

sparser
"Similar to the observations for DCC methylation, higher ESR1 methylation at specific sites was associated both with abnormal cytology and HPV 16 positivity."

sparser
"In terms of RPFT, there were significant associations with CCNA1 , DCC and NDN methylation in all HNSCC patients."

sparser
"While TBX5 and DCC are methylated in all cell lines, other genes ( TBX18, DGKI, PGRMC1, LIN7C and HOXB13 ) are differentially methylated ( xref )."

sparser
"In addition, we also performed multivariate Cox proportional hazards analysis to evaluate the prognostic value of FAM135B, ZNF610, HOXA9, 15 Accepted Manuscript and DCC methylation in OS and RFS of HNSCC by integration of clinical characteristics of HNSCC patients from TCGA."

sparser
"We investigated DCC methylation status in 98 gastric cancers and 105 normal gastric mucosa specimens."

sparser
"Therefore, we defined a DCC methylation of 5 % or more as a continuous variable (i.e., >5.0 % methylation was defined as methylation-positive (methylated) and <5.0 % methylation as methylation-negative (unmethylated))."

sparser
"CCNA1, DAPK, DCC and TIMP3 methylation were highly specific for being found in the OSCC samples."

sparser
"There were no significant associations between DCC methylation status and any other variables."

sparser
"Similarly to the DCC methylation status, we investigated associations between 18q LOH status and various clinicopathological and genetic features."

sparser
"Sato et al. [33] reported previously that DCC gene methylation occurred in 75% of primary gastric tumors and that the methylation status was significantly correlated with loss of DCC expression."

sparser
"However, experiments in the future need to confirm if methylated DCC can serve as a marker during the screening of cervical cancer ( xref )."

sparser
"DCC methylation in Q2 was associated with the highest probability of OST ( p -value = 0.005)."

sparser
"Interestingly, DCC methylation has been associated with head and neck squamous cell carcinoma xref and in one study, was found to be differentially methylated in head and neck cancer cell lines by HPV status xref ."

sparser
"For patients without methylated DCC, addition of a logistic regression score that was based on the five remaining genes improved sensitivity from 35.5% to 75% (95% CI: 64%, 84%) but decreased the specificity from 100% to 73% (95% CI:54%, 88%)."

sparser
"EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions."

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"A multivariate model analyzed risk classification and EDNRB, HOXA9 and DCC methylation status."

sparser
"DCC and EDNRB methylation status had again a significant association with a dysplasia/cancer diagnosis (OR=2.5, 95%CI=1.1-6.0; p=0.037 and OR=2.1, 95%CI=1.0-4.6; p=0.047, respectively) after adjusting for risk classification."

sparser
"For patients without methylated DCC, addition of a logistic regression score that was based on the five remaining genes improved sensitivity from 35.5% to 75% (95% CI: 64%, 84%) but decreased the specificity from 100% to 73% (54%, 88%) ( xref )."

sparser
"In a recent study of women undergoing routine cervical cancer screening in Appalachian Ohio, pyrosequencing of candidate genes revealed an association of DCC methylation with increased odds of abnormal cytology xref ."

sparser
"Further studies are needed to determine whether methylation of DCC can serve as a triage marker for cervical cancer screening."

sparser
"A similar pattern was observed for DCC methylation and RPFT, although with DCC , it was Q1 had much poorer probability of recurrence/persistence compared to other quartiles ( p-value  = 0.002). (Additional file xref : Figure S4)"

sparser
"When methylation of at least one of Kif1a , DCC , RARB , or NISCH was considered, methylation frequency was smoking-dependent; while none of the light- or non-smoker controls showed plasma DNA methylation, the cumulative smoking dose (pack-years) correlated well with the methylation frequency in cancer-free heavy smokers ( xref )."

sparser
"Moreover, DCC methylation was detected in two patients that also amplified EDNRB , and in one of these patients was also observed p16 methylation."

sparser
"When we categorized a cell line showing aΔC T of more than 15.0 as DCC expression-negative and a cell line with aΔC T of 15.0 or less as DCC expression-positive, only the GCIY cell line could be categorized as DCC expression-positive among the seven gastric cancer cell lines with DCC methylation; this finding was statistically non-significant."

sparser
"Seven of 8 cases with complete loss, 33 of 38 cases with focal loss, and 34 of 40 cases with positive DCC expression were informative for both DCC promoter methylation and 18q LOH."

sparser
"We found that among the cancers with complete loss of DCC expression, 5/7 cancers (71 %) demonstrated both DCC promoter methylation and 18q LOH."

sparser
"Among the 58 cancers with DCC alterations, 17 tumors showed alterations in both DCC methylation and 18q LOH, 19 had 18q LOH alone, and 22 cancers exhibited DCC methylation alone."

sparser
"In the salivary rinse samples collected without brush, primary tumor site was associated promoter methylation of CCNA1 ; and clinical TNM stage was associated with promoter methylation of CCNA1 and DCC ( xref )."

sparser
"The LOH ratio calculated for the other seven loci was significantly highest in gastric cancers with both DCC methylation and 18q LOH (mean LOH ratio, 0.44; SD ±0.39) and in cancers with 18q LOH alone (mean LOH ratio, 0.44; SD ±0.34), intermediate in cancers with DCC methylation alone (mean LOH ratio, 0.16; SD ±0.18), and lowest in cancers negative for DCC alterations (mean LOH ratio, 0.05; SD ±0.10; P  < 0.0001, Wilcoxon/Kruskal–Wallis test)."

sparser
"The authors observed the dynamic changes in methylated SEPT9 and DCC genes during neoadjuvant chemotherapy."

sparser
"DCC, DLC-1 and LRP1B were identified as tumor suppressor genes and were aberrantly methylated in cancer cells ( xref – xref )."

sparser
"On multivariable modeling, histological diagnosis was only independently associated with EDNRB (p=0.0003) or DCC (p=0.004) methylation."

sparser
"When we categorized gastric cancers with LOH ratios higher than 0 as CIN-positive, 12/17 gastric cancers (71 %) with both DCC methylation and 18q LOH, 13/17 gastric cancers (76 %) with 18q LOH alone, 12/22 gastric cancers (55 %) with DCC methylation alone, and 6/25 cancers (24 %) negative for DCC alterations were categorized as CIN-positive ( P  = 0.0025, Pearson’s chi-square test)."

sparser
"HOXA9 , EDNRB and DCC methylation were associated (p= 0.012; p<0.0001; p=0.0005) with premalignant or malignant disease."

sparser
"In combining the results from both DCC and EDNRB methylation assays, we observed improvement in performance, indicating their potential as biomarkers for HNSCC."

sparser
"The presence of EDNRB and/or DCC promoter methylation in salivary rinses compares well to examination by an expert clinician in risk classification of oral premalignant and malignant lesions."

sparser
"However, methylation of the DCC gene has recently been found in noncolorectal tumors."

sparser
"For EDNRB and DCC methylation, markers were previously shown to be methylated among 33%–67% of patients with HNSCC. xref , xref , xref In this study, the detection rate of oral rinse EDNRB methylation and DCC methylation was 78% and 76%, respectively, demonstrating that our method has a higher sensitivity toward detecting the finite methylation signal found in the oral rinse of the patients with HNSCC for the two markers."

sparser
"In this study, we analyzed esophageal squamous cell carcinoma (ESCC) cell lines and primary ESCCs as well as normal esophageal tissues for DCC methylation by bisulfite sequencing, methylation-specific PCR (MSP) and/or quantitative methylation-specific PCR (qMSP)."

sparser
"When a qMSP cut-off value for positivity was set to 1.0, DCC methylation was detected in 10 of 12 ESCC cell lines tested, 74% of primary ESCCs (n = 70), 0% of corresponding normal esophageal tissues (n = 20) and 0% of normal esophagus from healthy individuals (n = 19)."

sparser
"However, DCC methylation was not associated with any clinical or pathologic parameters measured."

sparser
"We have demonstrated that DCC methylation is a frequent and cancer-specific event in primary ESCCs, suggesting that DCC and associated pathways may represent a new diagnostical therapeutic target."

sparser
"A comparison among the methylation status of our hub genes is shown in Figure S2 Diagnostic and prognostic value of the four validated genes in TCGA cohort A ROC curve was plotted to evaluate the diagnostic value of FAM135B, ZNF610, HOXA9, and DCC methylation (Figure 6)."

sparser
"Promoter methylation of SFRP and DCC was elevated in T-47D-HNO relative to its parent cell line (p<0.05)."

sparser
"For patients without methylated DCC, addition of a logistic regression score that was based on the five remaining genes improved sensitivity from 35.5% to 75% but decreased the specificity from 100% to 73%."

sparser
"Interestingly, when we defined DCC and UNC5C methylation at 1 % or more as a continuous variable (i.e., >1.0 % methylation as methylation-positive (methylated) and <1.0 % methylation as methylation-negative (unmethylated)), only UNC5C methylation was significantly associated with the presence of the cagA sequence in normal gastric mucosa (data not shown), suggesting that inflammatory processes associated with H. pylori infection causes aberrant methylation in UNC5C promoter CpGs but not in the DCC promoter."

sparser
"In our previous study ( xref ), DCC methylation was detected in 54% of cases with 100% specificity in evaluation set and fell to 26% in the independent set."

sparser
"The results of this study indicate that in many hematological cell lines, the DCC, p51, and MGMT genes have been abnormally methylated in the CpG region."

sparser
"DCC methylation was correlated with bone invasion, and deep invasion of the tongue."

sparser
"Patients with primary oral cancer who had DCC methylation had a significantly shorter survival time than those who did not have DCC methylation."

sparser
"In CRCs, UNC5C and DCC methylation is associated with loss of gene expression [ xref , xref ]."

sparser
"Similarly, the plasma methylation of SEPT9 , DCC , BOLL , and SRFP2 showed stronger correlation with tumor burden than CEA and CA-19-9 [ xref ]."

sparser
"SSTR1 methylation was significantly correlated with tumor size ( P = 0.037), stage ( P = 0.037), galanin ( P = 0.030), GALR2 methylation ( P = 0.014), TAC1 methylation ( P = 0.023), TAC1R methylation ( P = 0.003), H-cadherin methylation ( P = 0.007), MGMT methylation ( P = 0.001), DAPK methylation ( P = 0.001) and DCC methylation ( P = 0.045) ( xref and xref )."

sparser
"DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients."

sparser
"Recent data suggests that detection of promoter methylation of EDNRB and DCC in patients with high-risk oral lesions has a similar performance in diagnosis as expert clinical evaluation [ xref ]."

sparser
"Nonetheless, tests utilizing DCC and EDNRB promoter methylation is limited to 46% sensitivity, and 72% specificity for cancer detection in salivary rinses [ xref ]."

sparser
"There was very little evidence of any significant associations of clinical characteristics with methylation of p16 , DCC , CCNA1 , CD1A , GADD45α , NDN or LINE-1 genes."

sparser
"In tumors of never smokers, CCNA1 methylation was higher (p<0.04) while DCC methylation tended to be lower (p=0.18)."

sparser
"The diagnostic performances of DCC , EDNRB , and ECAD promoter methylation analyses in saliva samples to differentiate patients in the derivation cohort from those in the control cohort were compared using ROC analysis (Fig.  xref )."

sparser
"Here, we found up-regulated methylation of NTN3, NTN4, NTN5, and NTNG1 and downstream genes UNC5C, UNC5D, DCC, and TP53 in breast cancer."

sparser
"Of note, methylation of p16, DCC, EDNRB and KIF1A varies across the amount of tobacco used ( xref )."

sparser
"With the cutoff for the DCC methylation value in saliva samples set at DCC NMV0.163, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy to detect hypopharyngeal cancer were 83.6%, 90.2%, 91.1%, 82.1%, and 86.6%, respectively (Fig.  xref )."

sparser
"In addition, methylation of DCC was correlated with bone invasion by gingival tumors (P = 0.036), with aggressive invasiveness of tumors of the tongue (P = 0.046), and with reduced survival (P = 0.050)."