ISYNA1: An Immunomodulatory-Related Prognostic Biomarker in Colon Adenocarcinoma and Pan-Cancer

Jia, Zeming; Wan, Xiaoping

doi:10.3389/fcell.2022.792564

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…On the other hand, ISYNA1 performed as a tumor suppressor in pancreatic cancer [12]. Evidence showed ISYNA1 acts as a protective factor in OC, high ISYNA1 expression predicted better DSS and longer OS time of ovarian cancer patients [14], this result was consistent with our observations. The inconsistent effects of ISYNA1 may be due to the differences between cancers and environments.…”

Section: Discussionsupporting

confidence: 91%

“…Current studies indicated that ISYNA1 may act either as an oncogene or tumor suppressor, depending on context. For example, in colon adenocarcinoma, ISYNA1 is a oncogene and a prognostic marker [14]. Overexpression of ISYNA1 promotes the proliferation and inhibits the apoptosis of bladder cancer cells [13].…”

Section: Discussionmentioning

confidence: 99%

“…Using multi-omics data from TCGA database, evidence showed ISYNA1 acts as a protective factor in ovarian cancer, and high expression of ISYNA1 predicted longer OS in ovarian cancer [14]. However, the cellular functions of ISYNA1 in OC and OCSCs have not been reported to the best of our knowledge.…”

Section: Introductionmentioning

confidence: 98%

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The myo-inositol biosynthesis rate-limiting enzyme ISYNA1 suppress the stemness of ovarian cancer

Yang

Cui

et al. 2023

Preprint

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Cancer stem cells (CSCs) play a central role in tumor formation, invasion, metastasis, chemoresistance and relapse of ovarian cancer (OC). Here we report myo-inositol biosynthesis rate-limiting enzyme (ISYNA1), as a suppressor of OC and regulate cancer stem-like properties of ovarian cancer cells. The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database results showed that lower ISYNA1 level was correlated with shorter overall survival (OS) in TCGA and GEO database. In GEO database, cancer tissues expressed lower level of ISYNA1 compared to normal tissues, and negative associated with the stemness markers. ISYNA1 deficiency promoting the growth, migration, invasion, and self-renewal capability of ovarian cancer cells. We also found that silencing ISYNA1 in ovarian cancer cells enhance CSC properties including sphere formation, the expression level of stem cell factors such as SOX2, NANOG and OCT4, as well as the expression of CSC markers CD44 and CD133, besides, the aldehyde dehydrogenase (ALDH) activity, CD44+/CD117+ expression also be analyzed. In contrast, ectopic overexpression of ISYNA1 suppress cell proliferation, migration, and invasion, decrease the stemness of ovarian cancer cells. In xenograft models, ISYNA1 deficiency significantly increases the tumorgenicity and CSC frequency. In addition, we identified P53 could regulate the expression of ISYNA1, and the myo-inositol addition rescue the stemness increased by ISYNA1 knockdown. In conclusion, these data establish the evidence of ISYNA1 as a suppressor of OC and a regulator of OCSCs, providing insight into potentially targetable pathways for ovarian cancer therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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The myo-inositol biosynthesis rate-limiting enzyme ISYNA1 suppress the stemness of ovarian cancer

Yang

Cui

et al. 2023

Preprint

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“…Previous studies have shown that high expression of DTYMK in HCC is associated with poor prognosis, and HCC cell lines with elevated DTYMK expression showed increased sensitivity to multiple chemotherapy agents such as sorafenib [ 50 ]. Conversely, in colon cancer, high expression of ISYNA1 has been linked to poor prognosis and resistance to most anticancer chemotherapy drugs [ 51 ]. Our findings align with those of Guo et al's study [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma

Chen,

Gao,

Zhang

et al. 2023

BMC Cancer

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Background Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC). Methods SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan–Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs). Results The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC. Conclusions Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC.

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The paradoxical role of inositol in cancer: a consequence of the metabolic state of a tumor

Case

Schmidtke

Greenberg

2022

Cancer Metastasis Rev

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ISYNA1: An Immunomodulatory-Related Prognostic Biomarker in Colon Adenocarcinoma and Pan-Cancer

Cited by 6 publications

References 17 publications

The myo-inositol biosynthesis rate-limiting enzyme ISYNA1 suppress the stemness of ovarian cancer

The myo-inositol biosynthesis rate-limiting enzyme ISYNA1 suppress the stemness of ovarian cancer

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma

The paradoxical role of inositol in cancer: a consequence of the metabolic state of a tumor

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