Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma

Jin, Yi-Xiang; Zhou, Xiaofen; Chen, Yingying; Jin, Weiwei; Wang, Yinghao; Ye, Dan-Rong; Sun, Yihan; Li, Yuefeng; Wang, Qingxuan; Zhang, Xiaohua; Wang, Ouchen; Chen, Endong

doi:10.7150/jca.28364

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…AKR1C2 expression is positively correlated with favorable tumor characteristics and prolongs survival time in primary breast cancer patients [ 34 ]. Elevated AKR1C2 expression also indicates a favorable prognostic and recurrence-free survival rate in papillary thyroid carcinoma [ 35 ]. Consistent with these studies, we identified that AKR1C2 is a tumor suppressor in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

SRSF3-Mediated Ki67 Exon 7-Inclusion Promotes Head and Neck Squamous Cell Carcinoma Progression via Repressing AKR1C2

Liu

Lin

Huang

et al. 2023

IJMS

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Ki67 is a well-known proliferation marker with a large size of around 350 kDa, but its biological function remains largely unknown. The roles of Ki67 in tumor prognosis are still controversial. Ki67 has two isoforms generated by alternative splicing of exon 7. The roles and regulatory mechanisms of Ki67 isoforms in tumor progression are not clear. In the present study, we surprisingly find that the increased inclusion of Ki67 exon 7, not total Ki67 expression level, was significantly associated with poor prognosis in multiple cancer types, including head and neck squamous cell carcinoma (HNSCC). Importantly, the Ki67 exon 7-included isoform is required for HNSCC cell proliferation, cell cycle progression, cell migration, and tumorigenesis. Unexpectedly, Ki67 exon 7-included isoform is positively associated with intracellular reactive oxygen species (ROS) level. Mechanically, splicing factor SRSF3 could promote exon 7 inclusion via its two exonic splicing enhancers. RNA-seq revealed that aldo-keto reductase AKR1C2 is a novel tumor-suppressive gene targeted by Ki67 exon 7-included isoform in HNSCC cells. Our study illuminates that the inclusion of Ki67 exon 7 has important prognostic value in cancers and is essential for tumorigenesis. Our study also suggested a new SRSF3/Ki67/AKR1C2 regulatory axis during HNSCC tumor progression.

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Section: Discussionmentioning

confidence: 99%

SRSF3-Mediated Ki67 Exon 7-Inclusion Promotes Head and Neck Squamous Cell Carcinoma Progression via Repressing AKR1C2

Liu

Lin

Huang

et al. 2023

IJMS

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“…For example, a novel oncolytic agent targeting ICAM1 against bladder cancer is now in phase 1 of a clinical trial [38]. Additionally, DNAH3 was identified as novel predisposition gene using exome sequencing in a Tunisian family with multiple non-BRCA breast cancer instances [35].…”

Section: Resultsmentioning

confidence: 99%

Expanding cancer predisposition genes with ultra-rare cancer-exclusive human variations

Rasnic

Linial

2020

Preprint

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It is estimated that up to 10% of cancer incidents are attributed to inherited genetic alterations. Despite extensive research, there are still gaps in our understanding of genetic predisposition to cancer. It was theorized that ultra-rare variants partially account for the missing heritable component. We harness the UK BioBank dataset of ~500,000 individuals, 14% of which were diagnosed with cancer, to detect ultra-rare, possibly high-penetrance cancer predisposition variants. We report on 115 cancer-exclusive ultra-rare variations (CUVs) and nominate 26 variants with additional independent evidence as cancer predisposition variants. We conclude that population cohorts are valuable source for expanding the collection of novel cancer predisposition genes.

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“…There are fewer articles on the role of TSC22D3 in gastric cancer. The expression of AKR1C2 (Aldo-Keto Reductases Family 1 Member C2) has been associated with the prognosis of a variety of diseases including thyroid cancer, acute myeloid leukaemia (AML) and esophageal squamous cell carcinoma (ESCC) [23][24][25] . Some articles have now shown that the expression of AKR1C2 is associated with immunostimulants, immunosuppressants, chemokines and receptors, and that as a ferroptosisrelated gene, the high expression of AKR1C2 correlates with a good prognosis in GC, which could potentially serve as a promising prognostic biomarker for GC patients [26] .…”

Section: Discussionmentioning

confidence: 99%

Prognostic analysis of disulfidptosis-based ferroptosis-related genes in gastric cancer

Shen

Huang

Jin

et al. 2023

Preprint

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Purpose Gastric cancer is one of the highly prevalent malignant tumours of the digestive tract in China and is highly lethal. Several studies have confirmed that Ferroptosis is closely related to the development of gastric cancer. disulfidptosis is a new type of cell death, which is a rapid death mode caused by disulfide stress induced by excessive cystine accumulation in the cell. Currently there are fewer studies on the discovery of disulfidptosis-related genes and their role in cancer development, and this study was used to explore the prognostic analysis of gastric cancer based on the disulfidptosis-related Ferroptosis genes. Methods The mRNA expression profiles of gastric cancer patients and corresponding clinical information were downloaded from the TCGA public database. Ferroptosis, disulfidptosis related gene ensembles were obtained from FerrDb database and published literature search. Differential expression analysis of genes was done on gastric cancer tissues and paracancerous tissues using the R package to screen out the disulfidptosis-related Ferroptosis-based genes with prognostic value. A prognostic model was constructed using LASSO Cox regression analysis, and the RiskScore of the corresponding genes was calculated, and the patients were classified into high-risk and low-risk groups according to the median value of the RiskScore. The predictive ability of the prognostic model for 1-year, 3-year, and 5-year survival was assessed by ROC curves. Multifactorial independent prognostic analysis was used to analyse the correlation between genes in the predictive model and clinicopathological features. The degree of immune infiltration of DEGs in gastric cancer tissues was analysed by Timer database. Results In the TCGA cohort, disulfidptosis-related Ferroptosis genes were differentially expressed between tumours and adjacent normal tissues. In this study, we constructed relevant prognostic models, including DUSP1, TSC22D3, AKR1C2, HNF4A, HELLS, SLC1A5, and BID, and divided the patients into two populations, high and low risk, according to the score of risk, and the overall survival rate of the high-risk group was significantly lower compared with that of the low-risk group (p < 0.001). In multifactorial Cox regression analysis, the risk score could be used as an independent prognostic factor (p < 0.05). The results of immune infiltration analysis showed that the expression level of each DEGs was significantly correlated with the level of immune cell infiltration in gastric cancer (p<0.05). Conclusion In this study, the disulfidptosis-related Ferroptosis gene prognostic model was constructed and identified as an independent prognostic factor, which provides a reference for the treatment and prognosis of gastric cancer patients.

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Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma

Cited by 8 publications

References 31 publications

SRSF3-Mediated Ki67 Exon 7-Inclusion Promotes Head and Neck Squamous Cell Carcinoma Progression via Repressing AKR1C2

SRSF3-Mediated Ki67 Exon 7-Inclusion Promotes Head and Neck Squamous Cell Carcinoma Progression via Repressing AKR1C2

Expanding cancer predisposition genes with ultra-rare cancer-exclusive human variations

Prognostic analysis of disulfidptosis-based ferroptosis-related genes in gastric cancer

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