Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach.
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ABSTRACT:
SUBMITTER: Zhu M
PROVIDER: S-EPMC9558685 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach.
Zhu Mengxuan M Chen Erbao E Yu Shan S Xu Chen C Yu Yiyi Y Cao Xin X Li Wei W Zhang Pengfei P Wang Yan Y Lian Baofeng B Zhang Shuirong S Qu Yueting Y Huang Lujia L Shi Weiwei W Cui Yuehong Y Qian Li L Liu Tianshu T
Cancer communications (London, England) 20220719 10
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Project description:BackgroundHepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique malignant gastric tumor with a significantly worse prognosis than non-hepatoid adenocarcinoma of the stomach (non-HAS). The present study explored the clinicopathological features of HAS and non-HAS patients to provide insights into HAS treatment strategies.MethodsFrom December 26, 2023, we performed a comprehensive search of the PubMed, Web of Science, Cochrane Library, and Embase.com databases for relevant studies. Two authors independently screened the studies, evaluated their quality, extracted data, and performed the analyses. This study was registered with PROSPERO on January 2, 2024.ResultsNine retrospective studies were included for analysis after screening 833 articles. A total of 350 and 924 patients were enrolled in the HAS and non-HAS groups, respectively. While no significant differences were observed in age, sex, tumor size, T3 or T4 stage, and N2 or N3 stage between the two groups, the HAS group exhibited higher rates of lymph node metastasis (OR = 1.93, 95% CI: 1.19-3.13, p = 0.007), liver metastasis (OR = 3.45, 95% CI: 2.26-5.28, p < 0.001), and vascular invasion (OR = 2.76, 95% CI: 2.05-3.71, p < 0.001). Additionally, the HAS group had lower 3-year survival rates (HR = 2.35, 95% CI: 1.70-3.25, p < 0.001) and 5-year survival rates (HR = 3.63, 95% CI: 1.49-8.88, p = 0.005), but lower rates of lymphatic permeation (OR = 0.68, 95% CI: 0.47-0.99, p = 0.040).ConclusionBased on the current clinical evidence, patients with HAS present distinct clinicopathological features, greater invasiveness, and poorer prognosis than non-HAS patients. Further research is warranted to develop optimal treatment strategies for HAS.
| S-EPMC11346349 | biostudies-literature
Project description:Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignancy with aggressive biological behavior. This study aimed to compare the genetic landscape of HAS with liver hepatocellular carcinoma (LIHC), gastric cancer (GC), and AFP-producing GC (AFPGC) and identify clinically actionable alterations. Thirty-eight cases of HAS were collected for whole-exome sequencing. Significantly mutated genes were identified. TP53 was the most frequently mutated gene (66%). Hypoxia, TNF-α/NFκB, mitotic spindle assembly, DNA repair, and p53 signaling pathways mutated frequently. Mutagenesis mechanisms in HAS were associated with spontaneous or enzymatic deamination of 5-methylcytosine to thymine and defective homologous recombination-related DNA damage repair. However, LIHC was characteristic of exposure to aflatoxin and aristolochic acid. The copy number variants (CNVs) in HAS was significantly different compared to LIHC, GC, and AFPGC. Aggressive behavior-related CNVs were identified, including local vascular invasion, advanced stages, and adverse prognosis. In 55.26% of HAS patients there existed at least one clinically actionable alteration, including ERBB2, FGFR1, CDK4, EGFR, MET, and MDM2 amplifications and BRCA1/2 mutations. MDM2 amplification with functional TP53 was detected in 5% of HAS patients, which was proved sensitive to MDM2 inhibitors. A total of 10.53% of HAS patients harbored TMB > 10 muts/Mb. These findings improve our understanding of the genomic features of HAS and provide potential therapeutic targets.
| S-EPMC9405706 | biostudies-literature
Project description:BackgroundTo investigate whether there is a distinct difference in prognosis between hepatoid adenocarcinoma of the stomach (HAS) and non-hepatoid adenocarcinoma of the stomach (non-HAS) and whether HAS can benefit from radical surgery.MethodsWe retrospectively reviewed 722 patients with non-HAS and 75 patients with HAS who underwent radical gastrectomy between 3 November 2009 and 17 December 2018. Propensity score matching (PSM) analysis was used to eliminate the bias among the patients in our study. The relationships between gastric cancer type and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox regression.ResultsOur data demonstrate that there was no statistically significant difference in the OS between HAS and non-HAS {K-M, P = log rank (Mantel-Cox), (before PSM P = 0.397); (1:1 PSM P = 0.345); (1:2 PSM P = 0.195)}. Moreover, there were no significant differences in the 1-, 2-, or 3-year survival rates between patients with non-HAS and patients with HAS (before propensity matching, after 1:1 propensity matching, and after 1:2 propensity matching).ConclusionHAS was generally considered to be an aggressive gastric neoplasm, but its prognosis may not be as unsatisfactory as previously believed.
| S-EPMC7368673 | biostudies-literature
Project description:PurposeHepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and aggressive tumor. The purpose of this study was to describe the clinical, computed tomography (CT), and prognostic features of HAS to increase the awareness of this entity and determine its distinguishing features from non-HAS tumors.MethodsThe CT features and clinical data of 47 patients in our hospital with pathologically documented HAS were retrospectively analyzed, and the relevant differences between pure HAS (pHAS) and mixed HAS (mHAS) were determined. In addition, 141 patients with non-HAS tumors in the same T stage in the same period were selected as the control group. The data were compared between the two groups, and factors affecting the prognosis of HAS were analyzed. In addition, we included 9 patients with HAS and 27 patients with non-HAS tumors from another center for external validation.ResultsThe patients in the HAS group were predominantly men (n = 33), and the tumor location was mostly the cardia or fundus (n = 27). Between the HAS and non-HAS groups, there were observed differences in terms of: sex, serum alpha-fetoprotein (AFP), carbohydrate antigen (CA)-125, and CA-724 levels; longest tumor diameter; degree of differentiation; vascular invasion; N stage, M stage, and tumor-node-metastasis (TNM) stage; thickest tumor diameter; plain CT attenuation; arterial-phase CT attenuation; CT attenuation between the venous and arterial phases; enhancement modes; and degrees of enhancement (all P < 0.05). In the data from another center for external validation, there were observed differences in terms of: age, degree of differentiation, vascular invasion, thickest tumor diameter, the ratio of arterial CT attenuation to CT attenuation of the abdominal aorta at the same level (RA), CT attenuation difference between the venous phase and arterial phase (HUv-a) (all P < 0.05). The results of the multivariate analysis revealed that the independent factors for differentiation were serum AFP level (P = 0.001), M stage (P = 0.038), and tumor enhancement on CT (P = 0.014). Among patients in the HAS group, 72.34% had pHAS and 27.66% had mHAS. The thickest tumor diameter and the longest short diameter of the metastatic lymph nodes of the mHAS group were on average 6.39 cm and 1.45 cm, respectively, which were larger than those in the pHAS group. The median progression-free survival time was 18.25 months in the HAS group, which was shorter than that in the non-HAS group (72.96 months; P = 0.001). The median overall survival time in the HAS group was 24.80 months, which was shorter than that in the non-HAS group (67.96 months; P = 0.001). The factors affecting the prognosis of HAS were M stage (P = 0.001), overall TNM stage (P = 0.048), presence of vascular cancer emboli (P = 0.040), and pHAS type (P = 0.046). Multifactorial analysis revealed that M stage (P = 0.027) and pHAS type (P = 0.009) were independent risk factors affecting the prognosis of HAS.ConclusionAlthough HAS is a rare clinical entity, it should be considered in the differential diagnosis of gastric tumors. Patients with HAS often have advanced-stage disease at presentation and a worse prognosis than patients with non-HAS tumors. CT findings, combined with laboratory results, can support the diagnosis of HAS. However, the final diagnosis needs to be confirmed with a histopathologic examination. If the postoperative pathologic findings reveal the mHAS type, a rapid clinical intervention and a detailed follow-up with CT are essential.
| S-EPMC8696206 | biostudies-literature
Project description:BackgroundPrevious studies found it difficult to differentiate hepatoid adenocarcinoma of the stomach (HAS) from conventional gastric adenocarcinoma (CGA). We aimed to assess the efficacy of a computed tomography (CT)-based radiomics nomogram in identifying HAS.MethodsPortal phase CT images were collected from 59 patients with HAS and 122 patients with CGA. HAS and CGA were differentiated through univariate analysis of clinical characteristics, serum biochemical biomarkers, and CT features. The construction of the radiomics signature involved the application of the least absolute shrinkage and selection operator (LASSO) regression model. Multivariable logistic regression analysis was employed to establish the CT-based radiomics nomogram.ResultsThe separation of HAS patients from CGA patients relied on the serum alpha-fetoprotein (AFP) level and radiomics signature. The area under the curve (AUC) of AFP was 0.726 [95% confidence interval (CI): 0.639-0.801] in the training cohort and 0.681 (95% CI: 0.541-0.800) in the test cohort, whereas the radiomic signature demonstrated a significantly higher AUC of 0.949 (95% CI: 0.895-0.980) in the training cohort and 0.868 (95% CI: 0.749-0.944) in the test cohort. The nomogram model yielded excellent accuracy for identifying HAS, achieving an AUC of 0.970 (95% CI: 0.923-0.992) in the training cohort and 0.905 (95% CI: 0.796-0.968) in the test cohort.ConclusionsRadiomics analysis offers promise for differentiating HAS from CGA, and the CT-based radiomics nomogram is likely to have significant clinical implications on HAS distinction.
| S-EPMC11565099 | biostudies-literature
Project description:ObjectivesHepatoid adenocarcinoma of the stomach (HAS) is characterized by histological resemblance to hepatocellular carcinoma and a poor prognosis. The aim of this study is to elucidate the clinicopathological and molecular characteristics of HAS.MethodsForty-two patients with HAS who received gastrectomy were enrolled in this study. Based on a panel of 483 cancer-related genes, targeted sequencing of 24 HAS and 22 clinical parameter-matched common gastric cancer (CGC) samples was performed. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analysed with the Kaplan-Meier method.ResultsThe most frequently mutated gene in both HAS and CGC was TP53, with a mutation rate of 30%. Additionally, CEBPA, RPTOR, WISP3, MARK1, and CD3EAP were identified as genes with high-frequency mutations in HAS (10-20%). Copy number gains (CNGs) at 20q11.21-13.12 occurred frequently in HAS, nearly 50% of HAS tumours harboured at least one gene with a CNG at 20q11.21-13.12. This CNG tended to be related to more adverse biobehaviour, including poorer differentiation, greater vascular and nerve invasion, and greater liver metastasis. Pathway enrichment analysis revealed that the HIF-1 signalling pathway and signalling pathways regulating stem cell pluripotency were specifically enriched in HAS. The survival analysis showed that a preoperative serum AFP level ≥ 500 ng/ml was significantly associated with poorer OS (p = 0.007) and tended to be associated with poorer DFS (p = 0.05).ConclusionCNGs at 20q11.21-13.12 happened frequently in HAS and tended to be related to more adverse biobehaviour. The preoperative serum AFP level was a sensitive prognostic biomarker for DFS and OS.
| S-EPMC6811386 | biostudies-literature
Project description: Not available
| S-EPMC11236608 | biostudies-literature
Project description:BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric cancer, but the role of perioperative chemotherapy is still poorly understood. The aim of this retrospective study was to investigate the associations between perioperative chemotherapy and prognosis of HAS.MethodWe retrospectively analyzed patients with locally advanced HAS who received radical surgery in Peking University Cancer Hospital between November 2009 and October 2020. Patients were divided into neoadjuvant chemotherapy-first (NAC-first) group and surgery-first group. The relationships between perioperative chemotherapy and prognosis of HAS were analyzed using univariate, multivariate survival analyses and propensity score matching analysis (PSM).ResultsA total of 100 patients were included for analysis, including 29 in the NAC-first group and 71 in the surgery-first group. The Her-2 amplification in HAS patients was 22.89% (19/83). For NAC-first group, 4 patients were diagnosed as tumor recession grade 1 (TRG1), 4 patients as TRG 2, and 19 patients as TRG 3. No significant difference in prognosis between the surgery-first group and the NAC-first group (P=0.108) was found using PSM analysis. In the surgery-first group, we found that the survival rate was better in group of ≥6 cycles of adjuvant chemotherapy than that of <6 cycles (P=0.013).ConclusionNAC based on platinum and fluorouracil may not improve the Overall survival (OS) and Disease-free survival time (DFS) of patients with locally advanced HAS. Patients who received ≥6 cycles of adjuvant chemotherapy had better survival. Therefore, the combination treatment of radical gastrectomy and sufficient adjuvant chemotherapy is recommended for patients with locally advanced HAS.
| S-EPMC8784750 | biostudies-literature
Project description:Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.
| S-EPMC10766033 | biostudies-literature
Project description: Not available
| S-EPMC10727808 | biostudies-literature