PTEN in Colorectal Cancer: Shedding Light on Its Role as Predictor and Target

Salvatore, Lisa; Calegari, Maria Alessandra; Loupakis, Fotios; Fassan, Matteo; Stefano, Brunella Di; Bensi, Maria; Bria, Emilio; Tortora, Giampaolo

doi:10.3390/cancers11111765

Cited by 62 publications

(53 citation statements)

References 79 publications

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“…40 PTEN participates in the regulation of cell division, proliferation, apoptosis, migration, adhesion to surrounding tissues, and neovascularization. 41 Increasing evidence indicates that PTEN expression is associated with the prognosis and drug response of several tumors, such as prostate cancer, breast cancer, and endometrial carcinoma. 42 Our results suggest that PTEN expression may be a prognostic and predictive biomarker for chordomas; nevertheless, we also noted that there was no significant correlation between copy number loss of PTEN and clinical prognosis.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of PTEN and CDKN2A Tumor-Suppressor Genes in Conventional and Chondroid Chordomas: Molecular Characteristics and Clinical Relevance

Yang¹,

Sun²,

Lei³

et al. 2020

OTT

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Introduction: Chordoma is a malignant tumor predominantly involving the skull base and vertebral column. This study aimed to investigate the molecular characteristics of PTEN and CDKN2A in conventional and chondroid chordomas and their correlation with clinical prognosis. Materials and Methods: A total of 42 patients were enrolled, including 26 patients with conventional chordoma and 16 patients with chondroid chordoma. Clinicopathological profiles and tissue specimens were collected. Gene sequencing and fluorescence in situ hybridization were performed to identify genetic alterations in the PTEN and CDKN2A genes. Immunohistochemical staining was used for semiquantitative evaluation of PTEN and CDKN2A expression. Results: Gene sequencing revealed an intron SNP (c.80-96A>G) and a missense mutation (c.10G>A; p.Gly4Arg) in the PTEN gene and a missense mutation (c.442G>A; p.Ala148Thr) in the CDKN2A gene. Loss of the PTEN locus was identified in 25 (59.5%) cases, and loss of the CDKN2A locus was found in 28 (66.7%) cases. There was no significant correlation between progression-free survival (PFS)/overall survival (OS) and loss of PTEN or CDKN2A. The patients with lower PTEN expression showed significantly shorter PFS and OS than those with higher expression, while there was no significant difference in PFS or OS between patients with lower CDKN2A expression and those with higher CDKN2A expression. Conclusion: Our findings delineated the genetic landscape and expression of PTEN and CDKN2A in chordomas. PTEN expression may serve as a prognostic and predictive biomarker for chordomas.

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Section: Discussionmentioning

confidence: 99%

Deficiency of PTEN and CDKN2A Tumor-Suppressor Genes in Conventional and Chondroid Chordomas: Molecular Characteristics and Clinical Relevance

Yang¹,

Sun²,

Lei³

et al. 2020

OTT

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“…Diagnostic and prognostic molecular biomarkers have revolutionized clinical strategies for the management of patients with cancer. While the majority of previous studies have primarily focused on genetic and expression markers of protein-coding genes (38)(39)(40), only a few studies have investigated the potential roles of miRNA as biomarkers for clinical assessments of different types of human cancer (41)(42)(43). A number of studies have performed differential expression analyses of miRNAs in several types of cancer to investigate the role of miRNAs as clinical biomarkers and identified some miRNAs whose aberrant expression levels are associated with pathological and clinical phenotypes of patients with cancer (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑126 is inversely correlated with insulin receptor substrate‑1 protein expression in colorectal cancer and is associated with advanced stages of disease

Zhang

et al. 2020

Oncol Lett

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Colorectal cancer (CRC) is a common human malignant tumor, and the fourth most common cause of cancer-associated mortality in China. However, the pathogenesis of CRC is not yet fully understood. The present study aimed to investigate the expression and clinical significance of microRNA (miR)-126 and insulin receptor substrate-1 (IRS-1), as well as the role of miR-126 in the prognosis of patients with CRC. A total of 86 colorectal tissue specimens, including 40 CRC and adjacent normal tissue, 26 colorectal adenoma tissue and 20 normal colorectal tissue samples, were collected for the present study. Reverse transcription-quantitative PCR analysis was performed to determine miR-126 and IRS-1 mRNA expression levels, while western blotting and immunohistochemistry (IHC) analyses were performed to determine IRS-1 protein expression levels. The correlation between miR-126 and IRS-1 expression, as well as the association between altered miR-126 and IRS-1 expression levels and clinicopathological characteristics, and the overall survival time of patients with CRC were assessed. The results demonstrated that miR-126 expression was significantly downregulated, while IRS-1 protein expression was upregulated in CRC tissues compared with that in adjacent normal tissues, colorectal adenoma tissues and normal colorectal tissues, respectively. IHC analysis exhibited strong positive staining of IRS-1 protein in CRC tissues, while absent or weak staining of IRS-1 protein was detected in adjacent normal tissues, colorectal adenoma tissues and normal colorectal tissues. miR-126 expression was inversely correlated with IRS-1 protein expression in CRC tissues (r=-0.420; P<0.05). Furthermore, downregulated miR-126 expression was associated with advanced clinicopathological characteristics of the disease and a shorter overall survival time in patients with CRC. Taken together, the results of the present study suggest that miR-126 downregulation may be a candidate molecular marker predictive of poor prognosis of patients with CRC.

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“…Since expression of PTEN undergoes downregulation in cancer cells, it has attracted much attention in the field of cancer therapy [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. PTEN was first discovered in 1997 when mutations were investigated at 10q23 locus in chromosome 10, and it was found that PTEN is an onco-suppressor gene [ 24 ].…”

Section: Pten Signaling: An Overviewmentioning

confidence: 99%

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

et al. 2020

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Cancer is one of the life-threatening disorders that, in spite of excellent advances in medicine and technology, there is no effective cure for. Surgery, chemotherapy, and radiotherapy are extensively applied in cancer therapy, but their efficacy in eradication of cancer cells, suppressing metastasis, and improving overall survival of patients is low. This is due to uncontrolled proliferation of cancer cells and their high migratory ability. Finding molecular pathways involved in malignant behavior of cancer cells can pave the road to effective cancer therapy. In the present review, we focus on phosphatase and tensin homolog (PTEN) signaling as a tumor-suppressor molecular pathway in gastric cancer (GC). PTEN inhibits the PI3K/Akt pathway from interfering with the migration and growth of GC cells. Its activation leads to better survival of patients with GC. Different upstream mediators of PTEN in GC have been identified that can regulate PTEN in suppressing growth and invasion of GC cells, such as microRNAs, long non-coding RNAs, and circular RNAs. It seems that antitumor agents enhance the expression of PTEN in overcoming GC. This review focuses on aforementioned topics to provide a new insight into involvement of PTEN and its downstream and upstream mediators in GC. This will direct further studies for evaluation of novel signaling networks and their targeting for suppressing GC progression.

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PTEN in Colorectal Cancer: Shedding Light on Its Role as Predictor and Target

Cited by 62 publications

References 79 publications

<p>Deficiency of <em>PTEN</em> and <em>CDKN2A</em> Tumor-Suppressor Genes in Conventional and Chondroid Chordomas: Molecular Characteristics and Clinical Relevance</p>

<p>Deficiency of <em>PTEN</em> and <em>CDKN2A</em> Tumor-Suppressor Genes in Conventional and Chondroid Chordomas: Molecular Characteristics and Clinical Relevance</p>

Downregulation of microRNA‑126 is inversely correlated with insulin receptor substrate‑1 protein expression in colorectal cancer and is associated with advanced stages of disease

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

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