INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer

Yuan, Jinpeng; Xie, Aosi; Cao, Qiangjian; Li, Xinxin; Chen, Juntian

doi:10.1155/2020/6909672

“…As a proteincoding gene, inhibin subunit beta B (INHBB) is involved in the synthesis of transforming growth factor-β (TGF-β) family members. INHBB expression has been found to be upregulated in colorectal cancer tissues and to be positively related to stromal and immune scores (Yuan et al, 2020). High RBP7 expression has been confirmed to be an independent biomarker for poor cancer-specific survival in patients with late-or early-stage colon cancer.…”

Section: Discussionmentioning

confidence: 94%

Identification of Distinct Molecular Patterns and a Four-Gene Signature in Colon Cancer Based on Invasion-Related Genes

Dong

¹

,

Shang

²

,

Ji

³

et al. 2021

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BackgroundThe pathological stage of colon cancer cannot accurately predict recurrence, and to date, no gene expression characteristics have been demonstrated to be reliable for prognostic stratification in clinical practice, perhaps because colon cancer is a heterogeneous disease. The purpose was to establish a comprehensive molecular classification and prognostic marker for colon cancer based on invasion-related expression profiling.MethodsFrom the Gene Expression Omnibus (GEO) database, we collected two microarray datasets of colon cancer samples, and another dataset was obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) further underwent univariate analysis, least absolute shrinkage, selection operator (LASSO) regression analysis, and multivariate Cox survival analysis to screen prognosis-associated feature genes, which were further verified with test datasets.ResultsTwo molecular subtypes (C1 and C2) were identified based on invasion-related genes in the colon cancer samples in TCGA training dataset, and C2 had a good prognosis. Moreover, C1 was more sensitive to immunotherapy. A total of 1,514 invasion-related genes, specifically 124 downregulated genes and 1,390 upregulated genes in C1 and C2, were identified as DEGs. A four-gene prognostic signature was identified and validated, and colon cancer patients were stratified into a high-risk group and a low-risk group. Multivariate regression analyses and a nomogram indicated that the four-gene signature developed in this study was an independent predictive factor and had a relatively good predictive capability when adjusting for other clinical factors.ConclusionThis research provided novel insights into the mechanisms underlying invasion and offered a novel biomarker of a poor prognosis in colon cancer patients.

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“…As a protein-coding gene, inhibin subunit β B (INHBB) is involved in the synthesis of transforming growth factor- β (TGF- β ) family members. Yuan et al found that overexpression of INHBB largely contributed to macrophage infiltration and impeded the infiltration of memory T cells, mast cells, and dendritic cells in colorectal cancer and was correlated with worse OS and DFS [ 40 ]. According to Chen et al [ 41 ], the growth and metastasis of an orthotopic hepatocellular carcinoma (HCC) tumor were promoted by the Sox9/INHBB axis, which activated peritumoral hepatic stellate cells (HSCs).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Robust Immune-Related Prognostic Signature for Gastric Cancer

Huo

¹

,

Wu

²

,

Zang

³

2021

Journal of Immunology Research

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Background. An increasing number of reports have found that immune-related genes (IRGs) have a significant impact on the prognosis of a variety of cancers, but the prognostic value of IRGs in gastric cancer (GC) has not been fully elucidated. Methods. Univariate Cox regression analysis was adopted for the identification of prognostic IRGs in three independent cohorts (GSE62254, n = 300 ; GSE15459, n = 191 ; and GSE26901, n = 109 ). After obtaining the intersecting prognostic genes, the three independent cohorts were merged into a training cohort ( n = 600 ) to establish a prognostic model. The risk score was determined using multivariate Cox and LASSO regression analyses. Patients were classified into low-risk and high-risk groups according to the median risk score. The risk score performance was validated externally in the three independent cohorts (GSE26253, n = 432 ; GSE84437, n = 431 ; and TCGA, n = 336 ). Immune cell infiltration (ICI) was quantified by the CIBERSORT method. Results. A risk score comprising nine genes showed high accuracy for the prediction of the overall survival (OS) of patients with GC in the training cohort ( AUC > 0.7 ). The risk of death was found to have a positive correlation with the risk score. The univariate and multivariate Cox regression analyses revealed that the risk score was an independent indicator of the prognosis of patients with GC ( p < 0.001 ). External validation confirmed the universal applicability of the risk score. The low-risk group presented a lower infiltration level of M2 macrophages than the high-risk group ( p < 0.001 ), and the prognosis of patients with GC with a higher infiltration level of M2 macrophages was poor ( p = 0.011 ). According to clinical correlation analysis, compared with patients with the diffuse and mixed type of GC, those with the Lauren classification intestinal GC type had a significantly lower risk score ( p = 0.00085 ). The patients’ risk score increased with the progression of the clinicopathological stage. Conclusion. In this study, we constructed and validated a robust prognostic signature for GC, which may help improve the prognostic assessment system and treatment strategy for GC.

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“…Inhibin subunit beta B gene ( INHBB ) encodes a pre-protein, which subsequently is processed to inhibin and activin [ 86 ]. Inhibin protein consists of a heterodimer formed by the two subunits α and β, which are secreted by ovarian granulosa cells and testicular Sertoli cells [ 162 ].…”

Section: Novel Methylation Biomarkers In Crc and Metastasis Prognosismentioning

confidence: 99%

“…In fact, INHBB is hypermethylated in CRC, and its expression was negatively correlated with methylation. Furthermore, the overexpression of INHBB is significantly and positively associated with invasion depth, distant metastasis, and CRC stage [ 86 , 167 ].…”

Section: Novel Methylation Biomarkers In Crc and Metastasis Prognosismentioning

confidence: 99%

Novel Methylation Biomarkers for Colorectal Cancer Prognosis

Gutierrez

¹

,

Demond

²

,

Brebi

³

et al. 2021

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Colorectal cancer (CRC) comprises the third most common cancer worldwide and the second regarding number of deaths. In order to make a correct and early diagnosis to predict metastasis formation, biomarkers are an important tool. Although there are multiple signaling pathways associated with cancer progression, the most recognized are the MAPK pathway, p53 pathway, and TGF-β pathway. These pathways regulate many important functions in the cell, such as cell cycle regulation, proliferation, differentiation, and metastasis formation, among others. Changes in expression in genes belonging to these pathways are drivers of carcinogenesis. Often these expression changes are caused by mutations; however, epigenetic changes, such as DNA methylation, are increasingly acknowledged to play a role in the deregulation of oncogenic genes. This makes DNA methylation changes an interesting biomarkers in cancer. Among the newly identified biomarkers for CRC metastasis INHBB, SMOC2, BDNF, and TBRG4 are included, all of which are highly deregulated by methylation and closely associated with metastasis. The identification of such biomarkers in metastasis of CRC may allow a better treatment and early identification of cancer formation in order to perform better diagnostics and improve the life expectancy.

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INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer

Cited by 34 publications

References 34 publications

Identification of Distinct Molecular Patterns and a Four-Gene Signature in Colon Cancer Based on Invasion-Related Genes

Identification of Distinct Molecular Patterns and a Four-Gene Signature in Colon Cancer Based on Invasion-Related Genes

Development and Validation of a Robust Immune-Related Prognostic Signature for Gastric Cancer

Novel Methylation Biomarkers for Colorectal Cancer Prognosis

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