Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population

Nakamura, Koki; Urabe, Yuji; Kagemoto, Kenichi; Yuge, Ryo; Hayashi, Ryohei; Ono, Atsushi; Hayes, C. Nelson; Oka, Shiro; Ito, Masanori; Nishisaka, Takashi; Tanabe, Kazuaki; Arihiro, Koji; Ohdan, Hideki; Tanaka, Shinji; Chayama, Kazuaki

doi:10.3390/cancers12020510

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…Consistently, LRP1 has been related to the poor prognosis of clear-cell renal cell carcinoma [ 58 ]. In addition, LRP1 mutation plays a key role in the occurrence of gastric cancer [ 59 ]. It has been demonstrated that the tPA-LRP1 pathway is a key switch for regulating the progression of melanoma by affecting the cellular composition and proteolytic makeup of the tumor niche [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel metabolism-related gene signature associated with the survival of bladder cancer

Shi

Huang

et al. 2021

BMC Cancer

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Background Bladder cancer (BC) is one of the most common malignancies and has a relatively poor outcome worldwide. In this study, we attempted to construct a novel metabolism-related gene (MRG) signature for predicting the survival probability of BC patients. Methods First, differentially expressed MRGs between BC and normal samples were identified and used to construct a protein-protein interaction (PPI) network and perform mutation analysis. Next, univariate Cox regression analysis was utilized to select prognostic genes, and multivariate Cox regression analysis was applied to establish an MRG signature for predicting the survival probability of BC patients. Moreover, Kaplan-Meier (KM) survival analysis and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive capability of the MRG signature. Finally, a nomogram based on the MRG signature was established to better predict the survival of BC. Results In the present study, 27 differentially expressed MRGs were identified, most of which presented mutations in BC patients, and LRP1 showed the highest mutation rate. Next, an MRG signature, including MAOB, FASN and LRP1, was established by using univariate and multivariate Cox regression analysis. Furthermore, survival analysis indicated that BC patients in the high-risk group had a dramatically lower survival probability than those in the low-risk group. Finally, Cox regression analysis showed that the risk score was an independent prognostic factor, and a nomogram integrating age, pathological tumor stage and risk score was established and presented good predictive ability. Conclusion We successfully constructed a novel MRG signature to predict the prognosis of BC patients, which might contribute to the clinical treatment of BC.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel metabolism-related gene signature associated with the survival of bladder cancer

Shi

Huang

et al. 2021

BMC Cancer

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“…Nakamura et al reported that LRP1 mRNA levels in gastric cancer with LRP1 mutations were significantly lower than those in gastric cancer without LRP1 mutations. Furthermore, CagA accumulation is significantly increased in gastric cancer tissues with LRP1 mutations [21]. Polymorphisms of LRP1 may be associated with CagA accumulation and atrophic gastritis.…”

Section: Table 4 (Continued)mentioning

confidence: 99%

“…Subsequently, autophagy degrades CagA. However, CAPZA1, a host protein, binds to the LRP1-ICD and inhibits LRP1-induced autophagy cancer [21]. Furthermore, Tsugawa et al reported that CAPZA1 overexpression reduced CagA degradation [20].…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in autophagy-related genes LRP1 and CAPZA1 may promote gastric mucosal atrophy

et al. 2023

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Background Helicobacter pylori secretes cytotoxin-associated gene A (CagA) into the gastric epithelium, causing gastric mucosal atrophy (GMA) and gastric cancer. In contrast, host cells degrade CagA via autophagy. However, the association between polymorphisms in autophagy-related genes and GMA must be fully elucidated. Results We evaluated the association between single nucleotide polymorphisms (SNPs) in autophagy-related genes (low-density lipoprotein receptor-related protein 1, LRP1; capping actin protein of muscle Z-line alpha subunit 1, CAPAZ1; and lysosomal-associated membrane protein 1, LAMP1) and GMA in 200 H. pylori-positive individuals. The frequency of the T/T genotype at rs1800137 in LRP1 was significantly lower in the GMA group than in the non-GMA group (p = 0.018, odds ratio [OR] = 0.188). The frequencies of the G/A or A/A genotype at rs4423118 and T/A or A/A genotype at rs58618380 of CAPAZ1 in the GMA group were significantly higher than those in the non-GMA group (p = 0.029 and p = 0.027, respectively). Multivariate analysis revealed that C/C or C/T genotype at rs1800137, T/A or A/A genotype at rs58618380, and age were independent risk factors for GMA (p = 0.038, p = 0.023, and p = 0.006, respectively). Furthermore, individuals with the rs1800137 C/C or C/T genotype of LRP1 had a 5.3-fold higher susceptibility to GMA. These genetic tests may provide future directions for precision medicine for individuals more likely to develop GMA. Conclusion LRP1 and CAPZA1 polymorphisms may be associated with the development of GMA.

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“…On the other hand, autophagy conversely reduces the intracellular VacA [ 12 ]. Focusing on the relationship between CagA and autophagy, the host’s autophagy degrades the CagA as a host defense mechanism [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

ATG16L1 and ATG12 Gene Polymorphisms Are Involved in the Progression of Atrophic Gastritis

Yamaguchi,

Sakaguchi,

Isomoto

et al. 2023

JCM

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Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337–1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required.

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Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population

Cited by 7 publications

References 34 publications

Identification of a novel metabolism-related gene signature associated with the survival of bladder cancer

Identification of a novel metabolism-related gene signature associated with the survival of bladder cancer

Polymorphism in autophagy-related genes LRP1 and CAPZA1 may promote gastric mucosal atrophy

ATG16L1 and ATG12 Gene Polymorphisms Are Involved in the Progression of Atrophic Gastritis

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