scholarly journals Intratumoral and peritumoral radiomics analysis for preoperative Lauren classification in gastric cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-Xiao Wang ◽  
Yi Ding ◽  
Si-Wen Wang ◽  
Di Dong ◽  
Hai-Lin Li ◽  
...  

Abstract Background Preoperative prediction of the Lauren classification in gastric cancer (GC) is very important to the choice of therapy, the evaluation of prognosis, and the improvement of quality of life. However, there is not yet radiomics analysis concerning the prediction of Lauren classification straightly. In this study, a radiomic nomogram was developed to preoperatively differentiate Lauren diffuse type from intestinal type in GC. Methods A total of 539 GC patients were enrolled in this study and later randomly allocated to two cohorts at a 7:3 ratio for training and validation. Two sets of radiomic features were derived from tumor regions and peritumor regions on venous phase computed tomography (CT) images, respectively. With the least absolute shrinkage and selection operator logistic regression, a combined radiomic signature was constructed. Also, a tumor-based model and a peripheral ring-based model were built for comparison. Afterwards, a radiomic nomogram integrating the combined radiomic signature and clinical characteristics was developed. All the models were evaluated regarding classification ability and clinical usefulness. Results The combined radiomic signature achieved an area under receiver operating characteristic curve (AUC) of 0.715 (95% confidence interval [CI], 0.663–0.767) in the training cohort and 0.714 (95% CI, 0.636–0.792) in the validation cohort. The radiomic nomogram incorporating the combined radiomic signature, age, CT T stage, and CT N stage outperformed the other models with a training AUC of 0.745 (95% CI, 0.696–0.795) and a validation AUC of 0.758 (95% CI, 0.685–0.831). The significantly improved sensitivity of radiomic nomogram (0.765 and 0.793) indicated better identification of diffuse type GC patients. Further, calibration curves and decision curves demonstrated its great model fitness and clinical usefulness. Conclusions The radiomic nomogram involving the combined radiomic signature and clinical characteristics holds potential in differentiating Lauren diffuse type from intestinal type for reasonable clinical treatment strategy.

Author(s):  
Han-Fang Cheng ◽  
Kuo-Hung Huang ◽  
Ming-Huang Chen ◽  
Wen-Liang Fang ◽  
Chien-Hsing Lin ◽  
...  

ObjectiveThe Lauren classification is an important histological classification of gastric cancer (GC) with different biological behaviors between histological types.BackgroundTo date, there are few reports on the genetic alterations and survival differences between different histological types according to the Lauren classification.MethodsIn total, 433 GC patients undergoing surgery were enrolled. The clinicopathological features, prognoses, and genetic alterations of the different Lauren types were compared.ResultsDiffuse-type GC was associated with a younger age, female predominance, more Borrmann type 3 and 4 tumors, more advanced pathological tumor (T) and node (N) categories, more tumor recurrences (especially peritoneal recurrence), and worse 5-year overall survival and disease-free survival rates than intestinal-type GC and mixed-type GC. Regarding genetic alterations, mixed-type GC was associated with more TP53 mutations than intestinal-type GC and diffuse-type GC. Multivariate analysis demonstrated the following independent prognostic factors: age, Lauren classification, and pathological T and N categories. Regarding mixed-type GC, diffuse-type major tumors were associated with more lymphovascular invasion, a more advanced N category and TNM stage, and fewer PI3K/AKT pathway mutations than intestinal-type major tumors.ConclusionsDiffuse-type GC had unfavorable clinicopathological features and a worse prognosis than intestinal-type GC. For mixed-type GC, the clinicopathological features and genetic alterations were different between intestinal-type major tumors and diffuse-type major tumors.


2021 ◽  
Vol 20 ◽  
pp. 153303382110455
Author(s):  
Jiahui Wang ◽  
Xin Liu ◽  
Hong-jin Chu ◽  
Ning Li ◽  
Liu-ye Huang ◽  
...  

This study aimed to investigate the expression and cellular function of the centromeric family of proteins (CENPs), especially centromere protein I (CENP-I), in gastric cancer (GC) and identified its clinical significance and cellular functions. CENP-I expression in GC was studied by cDNA microarray, quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC), and using datasets from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. Microarray and bioinformatic analyses identified upregulated CENP-A/E/F/H/I/K/P/W and HJURP in stomach adenocarcinoma (STAD), but not in signet ring cell carcinoma (SRCC). Significantly higher CENP-I mRNA expression was also confirmed in 40 pairs of GC tissues than in paired normal gastric tissues by qRT-PCR ( P<.001). IHC showed that elevated CENP-I expression was associated with higher tumor stage, lymph node invasion, increased HER2-positive rate (36.7% vs 10.0%), and intestinal Lauren classification in 69 GC samples compared to paired paracancerous normal tissues. The survival of the high-CENP-I group members was poor compared with that of the low-CENP-I group ( P = .0011). Cox univariate regression analysis identified tumor size ( P = .008), HER2 status ( P = .027), and CENP-I expression ( P = .049) were independent prognostic factors of GC. The cellular function of CENP-I was studied in MKN45 and MKN28 GC cell lines in vitro. Cell proliferation, migration, and apoptosis were determined using CCK-8, transwell assay, TUNEL assay, and flow cytometry. Our results showed that CENP-I promoted GC cell proliferation, inhibited apoptosis, facilitated cell migration, and induced epithelial–mesenchymal transition (EMT), possibly by activating the AKT pathway. CENP-I expression was correlated with genetic signatures of the proliferative subtype of GC, characterized by intestinal Lauren classification, HER2 amplification, and TP53 mutation. In conclusion, this study revealed an elevated CENP-I expression in GC, which was associated with malignant features and poor prognosis of GC patients, and identified its function in modulating cell proliferation, apoptosis, and migration.


2006 ◽  
Vol 21 (3) ◽  
pp. 162-169 ◽  
Author(s):  
T. Luebke ◽  
S.E. Baldus ◽  
D. Spieker ◽  
G. Grass ◽  
E. Bollschweiler ◽  
...  

Aim The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohisto-chemically assessed uPA and PAI-1 in patients with gastric cancer. Methods This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. Results Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). Conclusions Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.


2018 ◽  
Vol 25 (11) ◽  
pp. 3257-3263 ◽  
Author(s):  
Lin-Yong Zhao ◽  
Jun-Jiang Wang ◽  
Yong-Liang Zhao ◽  
Xin-Zu Chen ◽  
Kun Yang ◽  
...  

2020 ◽  
Vol 12 ◽  
pp. 175883592093035 ◽  
Author(s):  
Kunning Wang ◽  
Enxiao Li ◽  
Rita A. Busuttil ◽  
Joseph C. Kong ◽  
Sharon Pattison ◽  
...  

Background: The association between the survival or efficacy of chemotherapy and the Lauren subtype of gastric cancer (GC) remains unclear. We aimed to clarify whether patients with different Lauren subtypes have different survival after treatment with systemic chemotherapy: intestinal gastric cancer (IGC) patients survived better than patients with mixed type gastric cancer (MGC) or diffuse gastric cancer (DGC) after treatment with systemic chemotherapy. Patients & methods: Relevant studies for the meta-analysis were identified through searching Pubmed, Embase, Cochrane and Ovid up to March 2020. We also included our own prospectively collected cohort of patients that were followed over a 10-year period. Sub-group and sensitivity analyses were also performed. Results: In our prospective cohort, the overall survival (OS) of IGC patients receiving systemic chemotherapy (chemoIGC) [median OS 5.01 years, interquartile range (IQR) 2.63–6.71] was significantly higher than that of DGC patients receiving the same chemotherapy (chemoDGC) (median OS 1.33 years, IQR 0.78–3.33, p = 0.0001). After adjusting for age, gender and cancer stage, there was a significant difference in OS in patients treated with chemotherapy based on the Lauren classification of GC {hazard ratio (HR) for OS of the IGC versus DGC 0.33, [95% confidence interval (CI), 0.17–0.65; p < 0.001]}. In the IGC patients, the adjusted HR associated with chemotherapy was 0.26 (95% CI, 0.12–0.56; p = 0.001), whereas the association was 0.64 (95% CI, 0.30–1.33; p = 0.23) in the DGC patient group. In our meta-analysis, 33 studies comprising 10,246 patients treated with systemic chemotherapy (chemoIGC n = 4888, chemoDGC n = 5358) met all the selection criteria. While we accounted for much of the heterogeneity in these studies, we found that chemoIGC patients showed significantly improved OS [HR, 0.76 (95% CI, 0.71–0.82); p < 0.00001] when compared with similarly treated chemoDGC patients. Conclusion: Our results support the consideration of Lauren subtype when prescribing systemic chemotherapy for GC, particularly for MGC or DGC, which may not benefit from chemotherapy. Lauren classification should be considered to stratify chemotherapy regimens to GC patients in future clinical trials, with particular relevance to MGC or DGC, which is more difficult to treat with current regimens.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14526-e14526
Author(s):  
Mehmet Kucukoner ◽  
Erkan Arpaci ◽  
Abdurrahman Isikdogan ◽  
Mehmet Bilici ◽  
Dogan Uncu ◽  
...  

e14526 Background: The aims of this study were to evaluate the tolerability and toxicity with adjuvant chemoradiotherapy (CRT) and prognostic analysis of patients with operable gastric cancer. Methods: The retrospective analysis included 723 patients with operable gastric cancer, stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. Patients’ age, sex, tumor localization, Lauren classification, grade, stage, type of dissection, toxicity and tolerability status were analyzed. Results: 73.9% of the patients were with stage III- IVM0. 61.0% of the patients were in the intestinal type, 51.1% of the patients were with the distal type of gastric cancer and 61.4% of the patients had undergone D2 dissection. 545 (75.4%) of patients completed the entire of adjuvant CRT. The median follow-up period was 20.8 months. Overall Survival (OS) rates were 80% and 52% while relapse free survival (RFS) rates were 75% and 48%, at 1, 3 years, respectively. In univariate analysis of groups, according to the group under the age of 65 and above (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), toxicity (p=0.062 / p=0.077), tolerability of therapy (p=0.002 / p=0.001) were significantly different in both RFS and OS. In multivariate analysis, three independent prognostic factors were identified on RFS / OS; stage (ods ratio (OR)=3.0, 95% confidence interval (CI):1.8-5.0, / OR=3.2, CI=1.8-5.4), for Lauren classification (OR=1.5, CI=0.9-2.2 / OR=1.5, CI= 1.1-2.2), for tolerability of therapy (OR=2.0, CI=1.0-3.8 / OR=1.9, CI=1.0-3.6). Conclusions: We found a new independent prognostic factor whether or not tolerate adjuvant CRT because of toxicity, except for the known prognostic factors like tumor stage and Lauren classification. We suggest that the treatment of the patients with intolerable to adjuvant CRT, is to change with less toxic adjuvant therapies.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14670-e14670
Author(s):  
Metin Ozkan ◽  
Esra Ermis Turak ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
Veli Berk ◽  
...  

e14670 Background: HER-2 and Topo-2A genes are settled on a chromosome 17 and their co-amplification rates are high. In this study, early gastric cancer patients who received adjuvant chemo-radiotherapy and chemotherapy were evaluated with HER-2 and Topo-2A expression in association with clinical and histopathologic findings. Methods: A total of 103 gastric cancer patients were included the study. The HER-2 and Topo-2A levels were measured by immunohistochemistry in postoperative tumor materials. A standard evaluation method was admitted for HER-2 positivity, while Topo-2A nuclear staining 3+ and 4+ were considered as overexpression. Those with level 2+ or 3+ of HER-2, the FISH test were attempted. Results: The median follow-up was 19 months (ranges 2–70 months). Forty-six patients (44%) relapsed during follow-up whereas 60 patients (58%) had died. The median overall survival (mOS) was 23 months. Histopathologies of HER-2 positive patients were intestinal type in 7 (87.5%) and diffuse type in one (12.5%) patient. In the follow-up period 4 patients (50%) were died (mOS was 17 months in this group). Median overall survival was 23 months in HER-2 negative group (p=0.6). Histopathologies of Topo-2A positive patients were intestinal type in 9 (64.2%) and diffuse type in 5 (35.8%) patient. In the follow-up period 8 patients (57%) were died (mOS was 22 months in this group). Median overall survival was 23 months in Topo-2A negative group (p=0.8). Three patients (37.5%) who had HER-2 positive histopathologies also had Topo-2A positivity. Conclusions: Overexpression rates of HER-2 in gastric cancer were reported 6.8-34%. Racial differences and different scoring techniques thought to be impact the results. Co-amplification rate of HER-2 and Topo-2A was reported 34% in gastric cancer. In our study HER-2 and Topo-2A overexpression rates were 7.7% and 13.6% respectively and co-amplification of HER-2 with Topo-2A rate was 37.5% is also similar to the other studies. Stages of patients with HER-2 and Topo-2A overexpression were similar to the distribution of the overall patients. While intestinal subtypes showed a higher rate of HER-2 overexpression, the median survival times tend to be shorter in HER-2 positive patients.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 85-85
Author(s):  
Youjin Jang ◽  
Youjae Mok

85 Background: Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. A few of studies have examined the expression of ER in gastric cancer. However, considerable controversy is raised as to the expression level of ER and its prognostic value in gastric cancer. In the present study, the expression profile of ERα, ERβ was determined in gastric cancer cell lines according Lauren classification and evaluate that the treatment effect of selective estrogen receptor modulator. Methods: Using four cell lines established from human gastric carcinomas according Lauren classification, check endogenous ERα, ERβ expression levels with RT-PCR. The SERM treatment effect were detected MTT test. Using immunohistochemical detection, the present study analyzed the clinical relevance of ERα, ERβ expression in tumor cells in 197 patients who underwent curative radical surgery and who were observed on long-term follow-up. Results: Endogenous ERα was high expression not intestinal cancer cell lines but in diffuse cancer cell line. Endogenous ERβ was high expression both type cancer cell line than normal gastrointestinal cell lines. According MTT assay, only raloxifene among SERM was significant treatment effect. In immonohistochemial study of gastric tissue, ERα negative and ERβ positive was associated with good prognosis. Conclusions: ERβ may be partly involved in gastric carcinogenesis and ERβ antagonist might be new therapeutic drug for gastric cancer.


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