Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma
Abstract Background Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)‐related HCC. Methods In the present study,...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.7040 |
| _version_ | 1797205650706530304 |
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| author | Liming Qin Moqin Qiu Qiuling Lin Binbin Jiang Shicheng Zhan Xueyan Wei Junjie Wei Yingchun Liu Qiuping Wen Peiqin Chen Yanji Jiang Zihan Zhou Xiumei Liang Ji Cao Yizhen Gong Yuying Wei Xiaoxia Wei Hongping Yu |
| author_facet | Liming Qin Moqin Qiu Qiuling Lin Binbin Jiang Shicheng Zhan Xueyan Wei Junjie Wei Yingchun Liu Qiuping Wen Peiqin Chen Yanji Jiang Zihan Zhou Xiumei Liang Ji Cao Yizhen Gong Yuying Wei Xiaoxia Wei Hongping Yu |
| author_sort | Liming Qin |
| collection | DOAJ |
| description | Abstract Background Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)‐related HCC. Methods In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway‐related genes and overall survival (OS) of 866 patients with HBV‐related HCC. Results It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV‐related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose‐response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3‐year and 5‐year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10‐3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10−5 and 0.033, respectively). Conclusions Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV‐related HCC. |
| first_indexed | 2024-04-24T08:54:30Z |
| format | Article |
| id | doaj.art-9024f661ad5643d5a7a492f313f6f857 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-24T08:54:30Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-9024f661ad5643d5a7a492f313f6f8572024-04-16T08:48:34ZengWileyCancer Medicine2045-76342024-04-01137n/an/a10.1002/cam4.7040Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinomaLiming Qin0Moqin Qiu1Qiuling Lin2Binbin Jiang3Shicheng Zhan4Xueyan Wei5Junjie Wei6Yingchun Liu7Qiuping Wen8Peiqin Chen9Yanji Jiang10Zihan Zhou11Xiumei Liang12Ji Cao13Yizhen Gong14Yuying Wei15Xiaoxia Wei16Hongping Yu17Department of Experimental Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Respiratory Oncology Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Clinical Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Experimental Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Epidemiology and Health Statistics, School of Public Health Guangxi Medical University Nanning ChinaDepartment of Epidemiology and Health Statistics, School of Public Health Guangxi Medical University Nanning ChinaDepartment of Epidemiology and Health Statistics, School of Public Health Guangxi Medical University Nanning ChinaDepartment of Experimental Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Experimental Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Experimental Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Scientific Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Cancer Prevention and Control Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Disease Process Management Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Cancer Prevention and Control Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Clinical Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Experimental Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Clinical Research Guangxi Medical University Cancer Hospital Nanning ChinaDepartment of Experimental Research Guangxi Medical University Cancer Hospital Nanning ChinaAbstract Background Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)‐related HCC. Methods In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway‐related genes and overall survival (OS) of 866 patients with HBV‐related HCC. Results It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV‐related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose‐response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3‐year and 5‐year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10‐3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10−5 and 0.033, respectively). Conclusions Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV‐related HCC.https://doi.org/10.1002/cam4.7040hepatitis B virushepatocellular carcinomaNotch signaling pathwaysingle nucleotide polymorphismsurvival |
| spellingShingle | Liming Qin Moqin Qiu Qiuling Lin Binbin Jiang Shicheng Zhan Xueyan Wei Junjie Wei Yingchun Liu Qiuping Wen Peiqin Chen Yanji Jiang Zihan Zhou Xiumei Liang Ji Cao Yizhen Gong Yuying Wei Xiaoxia Wei Hongping Yu Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma Cancer Medicine hepatitis B virus hepatocellular carcinoma Notch signaling pathway single nucleotide polymorphism survival |
| title | Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma |
| title_full | Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma |
| title_fullStr | Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma |
| title_full_unstemmed | Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma |
| title_short | Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus‐related hepatocellular carcinoma |
| title_sort | association between novel genetic variants of notch signaling pathway genes and survival of hepatitis b virus related hepatocellular carcinoma |
| topic | hepatitis B virus hepatocellular carcinoma Notch signaling pathway single nucleotide polymorphism survival |
| url | https://doi.org/10.1002/cam4.7040 |
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