Dataset Information

Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.

ABSTRACT: Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n = 117) were drinkers or smokers, whereas 45% of the female patients (n = 33) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.

SUBMITTER: Onozato Y

PROVIDER: S-EPMC8505482 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.

Onozato Yusuke Y Sasaki Yu Y Abe Yasuhiko Y Sato Hidenori H Yagi Makoto M Mizumoto Naoko N Kon Takashi T Sakai Takayuki T Ito Minami M Umehara Matsuki M Koseki Ayumi A Ueno Yoshiyuki Y

Scientific reports 20211011 1

Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamo ...[more]

PMID: 34635759

Similar Datasets

Project description:IntroductionThe main risk factors for head and neck squamous cell carcinoma (HNSCC) are tobacco and alcohol consumption and human papillomavirus (HPV) infection. However, in a subset of patients, no risk factors can be identified. Glutathione S-transferase π (GTSP1) is a carcinogen-detoxifying enzyme that is activated by exposure to carcinogens, and it is associated with a reduction in response to toxic therapies. We studied the expression of GTSP1 in tumor and non-tumor tissue samples from patients with and without these risks to identify whether GTSP1 expression differs according to exposure to carcinogens.Materials and methodsNon-smoker/non-drinker (NSND) and smoker/drinker (SD) patients were matched according to age, gender, tumor site, TNM stage, grade and histological variants to establish 47 pairs of patients who have been previously tested for HPV. GTSP1 immunostaining was analyzed using a semi-quantitative method with scores ranging from 0 to 3 according to the area of immunostaining.ResultsGTSP1 expression was detected in the tumors of both groups. GTSP1 expression was higher in the non-tumor margins of SD patients (p = 0.004). There was no association between GTSP1 expression and positivity for HPV. No differences in survival were observed according to GTSP1 staining in tumors and non-tumor margins.ConclusionThis study showed that GTSP1 was expressed in tumors of HNSCC patients regardless of smoking, drinking or HPV infection status. The difference in GTSP1 expression in non-tumor margins between the two groups may have been due to two possible reasons. First, elevated GTSP1 expression in SD patients might be the result of activation of GTSP1 in response to exposure to carcinogens. Second, alternatively, impairment in the detoxifying system of GTSP1, as observed by the reduced expression of GTSP1, might make patients susceptible to carcinogens other than tobacco and alcohol, which may be the underlying mechanism of carcinogenesis in the absence of risk factors.

Project description:The lymphovascular invasion (LVI) status facilitates the determination of the optimal therapeutic strategy for superficial esophageal squamous cell carcinoma (SESCC), but in clinical practice, LVI must be confirmed by postoperative pathology. However, studies of the risk factors for LVI in SESCC are limited. Consequently, this study aimed to identify the risk factors for LVI and use these factors to establish a prediction model. The data of 516 patients who underwent radical esophagectomy between January 2007 and September 2019 were retrospectively collected (training set, n=361, January 2007 to May 2015; validation set, n=155, June 2015 to September 2019). In the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were utilized to identify predictive factors for LVI in patients with SESCC. A nomogram was then developed using these predictors. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the efficiency, accuracy, and clinical utility of the model. LASSO regression indicated that the tumor size, depth of invasion, tumor differentiation, lymph node metastasis (LNM), sex, circumferential extension, the presence of multiple lesions, and the resection margin were correlated with LVI. However, multivariate analysis revealed that only the tumor size, depth of invasion, tumor differentiation, and LNM were independent risk factors for LVI. Incorporating these four variables, model 1 achieved an AUC of 0.817 in predicting LVI. Adding circumferential extension to model 1 did not appreciably change the AUC and integrated discrimination improvement, but led to a significant increase in the net reclassification improvement (p=0.011). A final nomogram was constructed by incorporating tumor size, depth of invasion, tumor differentiation, LNM, and circumferential extension and showed good discrimination (training set, AUC=0.833; validation set, AUC=0.819) and good calibration in the training and validation sets. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. Thus, it is possible to predict the status of LVI using this nomogram scoring system, which can aid the selection of an appropriate treatment plan.

Project description:BackgroundAccurate prediction of tumor invasion depth in superficial esophageal squamous carcinoma (SESC) is essential for deciding the appropriate treatment strategy. We proposed novel endoscopic criteria to differentiate between mucosal and submucosal esophageal cancers and to evaluate the diagnostic accuracy and usefulness of the criteria.MethodsA total of 352 patients who underwent endoscopic or surgical resection for SESC between 1991 and 2010 were included. First, the novel endoscopic criteria were created based on the endoscopic features of 60 randomly selected patients as follows: for T1m cancers, I. flat or slightly elevated or depressed lesion with smooth/even surface of any size, II. slightly elevated lesion of ≤ 1 cm with granular or uneven surface, III. hyperemic flat lesion of ≤ 3 cm with granular or uneven surface, IV. slightly depressed lesion of ≤ 2 cm with uneven surface and for T1sm cancers, I. irregularly (unevenly) nodular or protruded lesion of any size, II. slightly elevated lesion of > 1 cm with granular or uneven surface, III. hyperemic flat lesion of > 3 cm with granular or uneven surface, IV. irregularly (unevenly) depressed lesion of > 2 cm, and V. ulcerative lesion of any size. Next, the endoscopic findings of the remaining 292 patients were reviewed according to the criteria.ResultsThe accuracy of novel endoscopic criteria was 79.5% (232/292). The sensitivity and specificity of mucosal cancers were 78.4% and 81.0%, respectively, whereas those for submucosal cancers were 81.0% and 78.4%, respectively. The accuracy for mucosal cancers was high (97.3%, 72/74) when the lesions were flat or slightly elevated/depressed with smooth/even surface regardless of size, whereas that for submucosal cancers was high (85.7%, 18/21) when the lesions were irregular/nodular protrusions regardless of size. In multivariate analysis, macroscopic type IIb lesion was identified as an independent factor affecting accuracy (P < 0.05). The difference in recurrence-free survival rates between endoscopically mucosal and submucosal cancers was significant (P = 0.026).ConclusionThe novel endoscopic criteria appear to be accurate and useful in predicting invasion depth in SESC. Our criteria might help not only to decide the treatment strategy between surgery and endoscopic resection but also to predict the outcomes of SESC.

Dataset Information

Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.

Publications

Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets