scholarly journals Transcriptome Analysis and the Prognostic Role of NUDC in Diffuse and Intestinal Gastric Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110195
Author(s):  
Sang-Ho Jeong ◽  
Miyeong Park ◽  
Sun Yi Park ◽  
Jiho Park ◽  
Tae-Han Kim ◽  
...  

Introduction: There have been few studies about gene differences between patients with diffuse-type gastric cancer and those with intestinal-type gastric cancer. The aim of this study was to compare the transcriptomes of signet ring cell gastric cancer (worst prognosis in diffuse-type) and well-differentiated gastric cancer (best prognosis in intestinal-type); NUDC was identified, and its prognostic role was studied. Materials and Methods: We performed next-generation sequencing with 5 well-differentiated gastric cancers and 3 of signet ring cell gastric cancer surgical samples. We performed gene enrichment and functional annotation analysis using the Database for Annotation, Visualization and Integrated Discovery bioinformatics resources. Immunohistochemistry was used to validate NUDC expression. Results: Overall, 900 genes showed significantly higher expression, 644 genes showed lower expression in signet ring cell gastric cancer than in well-differentiated gastric cancers, and there was a large difference in adhesion, vascular development, and cell-to-cell junction components between the 2 subtypes. We performed variant analysis and found 52 variants and 30 cancer driver genes, including NUDC. We analyzed NUDC expression in gastric cancer tissue and its relationship with prognosis. Cox proportional hazard analysis identified T stage, N stage, and NUDC expression as independent risk factors for survival ( P < 0.05). The overall survival of the NUDC-positive group was significantly higher (53.2 ± 0.92 months) than that of the NUDC-negative group (44.6 ± 3.7 months) ( P = 0.001) in Kaplan-Meier survival analysis. Conclusion: We found 30 cancer driver gene candidates and found that the NUDC-positive group showed significantly better survival than the NUDC-negative group via variant analysis.

2011 ◽  
pp. 21-29
Author(s):  
Viet Nho Le ◽  
Van Huy Tran ◽  
Cong Thuan Dang ◽  
Van To Ta

Objective: HER2 may have a prognostic value in gastric cancer and test for HER2 overexpression help to select the patients for the targeted therapy with trastuzumab. Our aim was to study endoscopic properties, histopathology of gastric adenocarcinoma and their relationship with HER2 overexpression. Materials and Methods: Between 3/2010 and 05/2011, 64 patients with gastric cancer were tested for HER2 status by immunohistochemical staining of formalin-fixed paraffin-embedded endoscopic biopsy samples. Design: Cross-sectional study. Results: According to Borrmann, polypoid, fungating, ulcerated, and infiltrative type cancer. According to Lauren’s classification, 42.2% were intestinal, 57.8% were diffuse. According to WHO, 43.8% were tubular adenocarcinoma, 7.8% were mucinous adenocarcinoma, 17.2% were signet-ring cell carcinoma, and 31.3% were undifferentiated carcinoma. 29.7% were well-differentiated tumors, 18.8% were moderately-differentiated tumors, and 51.6% were poorly-differentiated tumors. HER2 overexpression was present in 23.5% of gastric carcinomas. 40% cardia tumors and 22% non-cardia tumors were HER2 positive. HER2 overexpressions were different between polypoid, fungating, ulcerated, and infiltrative types with rate of 30.8%, 37%, 6.3% and 0%, respectively (p = 0.04). HER2 overexpression of intestinal type tumors was higher than diffuse type tumors (37% vs 13.5%, p=0.04). HER2 overexpression in tubular adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and undifferentiated carcinoma was 35.7%, 9.1%, 20% and 15%, respectively. 36.8% of well-differentiated tumors, 33.3% moderately-differentiated tumors, and 12.1% of poorly-differentiated tumors overexpress HER2. Conclusions: HER2 overexpression was found in 23.5% of gastric carcinomas and was associated to endoscopic properties, histopathologic type of tumors. Keywords: HER2, gastric cancer.


2004 ◽  
Vol 128 (7) ◽  
pp. 765-770 ◽  
Author(s):  
Donald Earl Henson ◽  
Christopher Dittus ◽  
Mamoun Younes ◽  
Hong Nguyen ◽  
Jorge Albores-Saavedra

Abstract Context.—During the last 50 years, the incidence and mortality of gastric cancer has declined in many countries. This decline has primarily included the intestinal type (Lauren classification). However, there is an impression among pathologists that the diffuse type, especially the signet ring cell subtype, has become more prevalent. Objectives.—Using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, we analyzed the trends of the 2 primary types (intestinal and diffuse) of gastric carcinomas from 1973 through 2000. Design.—Trends in age-adjusted rates were determined for gastric carcinomas through the SEER statistical program (SEER*Stat), which is available on the Internet to the public. Results.—During the period studied, the intestinal type continued to decline in males, females, African Americans, and whites. The intestinal type was more common in males than in females and more common in African Americans than in whites. In contrast, a consistent increase in the rate of the diffuse type of gastric carcinoma was seen during this period. The rate increased from 0.3 cases per 100 000 persons in 1973 to 1.8 cases per 100 000 persons in 2000. This increase was seen in males, females, African Americans, and whites. The predominant increase occurred in the signet ring type. Conclusions.—The results indicate a progressive decrease in the incidence of the intestinal type of gastric cancer and an increase in the diffuse type of gastric carcinoma, especially the signet ring cell type. The clinical implications of the increase are considered.


2020 ◽  
Author(s):  
Hiroaki Tanaka ◽  
Mami Yoshii ◽  
Yuichiro Miki ◽  
Tatsuro Tamura ◽  
Takahiro Toyokawa ◽  
...  

Abstract Background: Since 1965, the Laurén classification has been used most commonly for gastric adenocarcinoma, with two types, intestinal type and diffuse type. Signet ring cell carcinoma (Sig) and non-solid poorly differentiated adenocarcinoma (Por2) are the histological forms of diffuse type and are often found in advanced tumors, and they seem to be associated with a poor prognosis. S-1 based adjuvant chemotherapy for patients with stage II/III gastric cancer has generally been accepted in Japan, but histological type does not alter treatment strategy. The aim of the present study was to investigate the prognostic impact of the histopathologic mixture of Sig and Por2 in patients with stage II/III gastric cancer treated with S-1 adjuvant chemotherapy.Methods: The clinicopathological data of 968 gastric carcinoma patients who underwent gastrectomy between 2007 and 2016 at our department were retrospectively analyzed. In this study, tumors containing Sig or Por2 were classified as Diffuse type, and those not containing them were classified as Intestinal type.Results: There were 307 cases of Diffuse type and 661 of Intestinal type. Diffuse type included 189 cases with Sig. Pathological diagnosis of Sig was an independent risk factor for peritoneal recurrence in patients with stage II/III. Patients with Diffuse type had worse overall survival than those with Intestinal type in Stage III. Of the patients who received S-1 adjuvant chemotherapy, the prognosis of Stage III patients with Sig but not Por2 was Significantly worse compared to patients with Intestinal type.Conclusions: The coexistence of Signet ring cell carcinoma in the primary tumor was associated with a poor prognosis in patients with stage III gastric cancer. These findings suggest that, because mixed Sig gastric cancer had a high risk of peritoneal recurrence even if adjuvant chemotherapy were performed, the pathological diagnosis should be considered when determining the therapeutic strategy for adjuvant chemotherapy in stage III gastric cancer.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 135-135
Author(s):  
Rosalba Barile ◽  
Michela Squadroni ◽  
Federica Brena ◽  
Eleonora Cerchiaro ◽  
Valeria Zurlo ◽  
...  

135 Background: Medical management of advanced GC is mostly dependent on prognostic assessment based on tumor stage (TNM) and clinical patients (pts)’ characteristics, other than HER2 expression. Prognostic and predictive factors are clearly needed, and histotype could be proposed as a surrogate marker of disease biology. Methods: We retrospectively analyzed pts with advanced GC treated with first line chemotherapy (CT) at Oncology Unit of Humanitas Gavazzeni (Bergamo) and Policlinico Gemelli (Roma). Pts were divided in three subgroups according to histological diagnosis: diffuse type carcinoma, intestinal type carcinoma and signet ring cell carcinoma. HER2 positive tumors were excluded from the analysis. The aim of our analysis was to compare clinical outcomes of metastatic GC pts receiving first line CT according to histological classification (overall survival: OS and Progression Free Survival: PFS). Results: We analyzed 170 pts. Histological diagnosis was as follows: 24.1% (n=41) signet ring cell, 54.4% (n=92) diffuse type, 21.1%(n=37) intestinal type. Pts received a fluoropyrimidine-based doublet containing cisplatin, oxaliplatin or irinotecan; in three drugs regimen anthracycline was added. In diffuse type subgroup OS was: 11.3 months with oxaliplatin based CT, 7.3 months in cisplatin and 6.2 months in irinotecan (p=0.0054); PFS was 5.2, 3.5 and 4.4 months for oxaliplatin, cisplatin and irinotecan based CT respectively (p=0.0036). In signet ring cell carcinomas OS was 12.1 months with oxaliplatin 13.9 with irinotecan, and 5.6 months with cisplatin (p=0.04), and PFS was 6.5, 8.5 and 2.9 months in pts treated with oxaliplatin, cisplatin and irinotecan respectively (p=0.0008). Among pts with intestinal type we did not detect any significant difference in term of OS and PFS comparing first line schedules. Conclusions: Based on our results, histology may be used as a simple, costless and easy tool in advanced gastric cancer treatment management. Clinical use of biomarkers (with the exception for HER2) which are being evaluated as prognostic or predictive factors in GC, is still controversial. In this scenario, the prognostic / predictive value of histology could play a significant role in treatment decision making.


1996 ◽  
Vol 99 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Tatsuhiro Shibata ◽  
Atsushi Ochiai ◽  
Masahiro Gotoh ◽  
Rikuo Machinami ◽  
Setsuo Hirohashi

2021 ◽  
Author(s):  
Donglang Jiang ◽  
Xing Chen ◽  
Zhiwen You ◽  
Hao Wang ◽  
Xiaoyun Zhang ◽  
...  

Abstract Introduction Early and precise diagnosis and staging of gastric cancer are important for its treatment and management. However, the low sensitivity of 18F-fluorodeoxyglucose (18F-FDG) for gastric cancer diagnosis limits its application. Currently, the tracer 68Ga-FAPI, which targets fibroblast activation protein (FAP), is widely used to diagnose various cancers. However, the diagnostic value of 68Ga-FAPI in gastric cancer is still unclear. In this study, we aimed to investigate the potential advantage of 68Ga-FAPI-04 over 18F-FDG in the evaluation of gastric cancer.Methods: Thirty-eight patients with gastric cancer (31 with adenocarcinoma and 7 with signet ring cell carcinoma) were recruited for this study. All of the participants underwent 68Ga-FAPI-04 and 18F-FDG imaging by positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance (MR). The results were interpreted by two experienced nuclear medicine physicians, and the maximum standardized uptake value (SUVmax) was calculated.Results: For the detection of primary gastric cancer, the sensitivities of 68Ga-FAPI-04 PET and 18F-FDG PET were 100% (38/38) and 81.6% (31/38), respectively. Four cases of adenocarcinoma and three cases of signet ring cell carcinoma were missed by 18F-FDG PET. The SUVmax of 68Ga-FAPI-04 in tumors greater than 4 cm (11.0 ± 4.5) was higher than tumors less than 4 cm (4.5 ± 3.2) (P = 0.0015). The SUVmax of 68Ga-FAPI-04 was higher in T2-4 tumors (9.7 ± 4.4) than in T1 tumors (3.1 ± 1.5) (P = 0.0002). For the detection of metastatic lesions, the sensitivities of 68Ga-FAPI-04 PET and 18F-FDG PET in 10 patients with regional lymph node metastasis and distant metastasis were 6/10 and 5/10, respectively.Conclusion: Compared to 18F-FDG PET, 68Ga-FAPI-04 PET had superior potential in detecting primary gastric cancers and metastatic lymph nodes, 68Ga-FAPI-04 PET also had a better performance on small gastric cancer detection. 68Ga-FAPI-04 PET could provide better performance for gastric cancer diagnosis and staging.


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