Clinicopathological Significance of Elevated PIK3CA Expression in Gastric Cancer

Jang, Si‐Hyong; Kim, Kyung-Ju; Oh, Mee‐Hye; Lee, Jihye; Lee, Hyun Ju; Cho, Hyun Deuk; Han, Sun Wook; Son, Myoung Won; Lee, Moon Soo

doi:10.5230/jgc.2016.16.2.85

Cited by 15 publications

(13 citation statements)

References 27 publications

(43 reference statements)

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“…Furthermore, the protein expression level of PIK3CA was identified to be correlated with tumor differentiation, lymphatic metastasis and depth of invasion; however, our previous study suggested that the protein expression level of PIK3CA was associated only with the depth of invasion (14). The present study suggested that the protein expression level of PIK3CA may be associated with the development of gastric cancer, consistently with previous findings (23,24).…”

Section: Discussionsupporting

confidence: 93%

Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

Zhou

Tan

et al. 2019

Mol Med Report

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AT-rich interaction domain 1A (ARID1A) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) serve important roles in the formation and development of numerous malignancies including gastric cancer. Accumulating evidence has demonstrated that Epstein-Barr virus (EBV) is a pathogenic virus associated with gastric cancer. The present study aimed to investigate the association between EBV infection, and the expression levels of ARID1A and PIK3CA in gastric cancer. EBER in situ hybridization was performed to detect EBV infection. Immunohistochemistry was used to assess the expression levels of ARID1A and PIK3CA in gastric cancer and adjacent normal tissues. A total of 58 gastric cancer and 10 adjacent normal tissues were tested for genetic mutations via single nucleotide polymorphism genotyping assays. Fluorescent polymerase chain reaction was used to detect EBV infection; 9.3% (28/300) of gastric cancer samples were positive for EBV, whereas, all adjacent normal tissues were negative. ARID1A and PIK3CA were negatively correlated in gastric cancer (r=−0.167). The expression levels of ARID1A and PIK3CA in gastric cancer were significantly associated with the depth of invasion of gastric cancer. A total of 62.1% (36/58) of tumor samples exhibited mutations in ARID1A, whereas, 13.8% (8/58) presented mutations in PIK3CA. Notably, EBV-associated gastric cancer (EBVaGC) samples with PIK3CA mutations additionally exhibited ARID1A mutations. Although in the present study it was identified that ARID1A and PIK3CA were negatively correlated in EBVaGC, further studies are required to investigate the association among ARID1A, PIK3CA and EBV in gastric cancer.

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Section: Discussionsupporting

confidence: 93%

Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

Zhou

Tan

et al. 2019

Mol Med Report

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“…When it refers to the different treatment settings, subgroup analysis showed that in the radical resection and palliative surgery mixed group [ 12 , 17 , 19 ], the association between PIK3CA overexpression and overall survival remains significant (HR = 2.13, 95% CI 1.67–2.72, p < 0.001), while in the radical resection-only group [ 15 , 16 , 20 ], it was not significant (HR = 1.25, 95% CI 0.86-1.83, p =0.246), which might indicate a more predominant role of PIK3CA overexpression predication on survival in those patients with late-stage diseases.…”

Section: Resultsmentioning

confidence: 99%

Association between PIK3CA alteration and prognosis of gastric cancer patients: a meta-analysis

Chen

et al. 2018

Oncotarget

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BackgroundIncreasing evidence suggests that dysregulation of phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) plays an important role in carcinogenesis. However, the relationship between PIK3CA expression and gastric cancer (GC) prognosis remains controversial.MethodsWe searchedPubMed, Embase, Web of Science, and the Cochrane Library databases for relevant studies up to June 30, 2017. Primary outcomes were hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) for association with overall survival and clinicopathological features.ResultsEleven studies comprising 2481 GC patients were analyzed. Pooled analysis showed that PIK3CA upregulation was significantly associated with worse overall survival (HR = 1.79, 95% CI 1.42–2.27, p< 0.001) at the protein (HR = 1.94, 95% CI 1.52–2.47, p< 0.001) but not the gene (HR = 1.57, 95% CI 0.92–2.69, p= 0.097) level. PIK3CA gene mutation did not correlate with overall survival (HR = 1.05, 95% CI 0.83–1.34, p= 0.666) but was significantly associated with poor tumor differentiation (OR = 0.37, 95% CI 0.17–0.76, p= 0.011).ConclusionHigh PIK3CA protein expression predicted poor prognosis in GC, whereas PIK3CA gene amplification or mutation did not. Moreover, PIK3CA mutation was an indicator of poorly differentiated tumors.

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“…PIK3CA mutations were associated with Akt activation and high tumor aggressiveness in gastric cancer ( 24 ). In addition, high PIK3CA expression was significantly associated with tumor invasiveness, phenotype and poor patient survival ( 25 ). Unlike previous studies using quantitative PCR ( 24 ) or IHC ( 25 ) for the PIK3CA alterations only, the present study confirmed that PIK3CA mutation and amplification in gastric cancer were associated with adverse clinical manifestation using multi-gene analysis.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, high PIK3CA expression was significantly associated with tumor invasiveness, phenotype and poor patient survival ( 25 ). Unlike previous studies using quantitative PCR ( 24 ) or IHC ( 25 ) for the PIK3CA alterations only, the present study confirmed that PIK3CA mutation and amplification in gastric cancer were associated with adverse clinical manifestation using multi-gene analysis. The results of the present gene panel study demonstrated that AGC with mutated PIK3CA tended to be of an advanced TNM T stage (T4a, 88%), compared with AGC with wild-type PIK3CA (57%) or with mutations other than PIK3CA (72%), although Epstein-Barr virus (EBV) in situ hybridization was not investigated; a previous study demonstrated that PIK3CA mutations were more dispersed in EBV-positive cancer, but localized in the kinase domain (exon 20) in EBV-negative cancer ( 5 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic profiling of somatic alterations by Oncomine Focus Assay in Korean patients with advanced gastric cancer

et al. 2020

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Gastric cancer is one of the leading causes of cancer-associated death; however, analysis of its molecular and clinical characteristics has been complicated by its histological and etiological heterogeneity. The present study aimed to estimate somatic mutation profiling in gastric cancer. To do so, targeted next-generation sequencing (NGS) was performed with the Oncomine Focus Assay to compare the clinicopathological characteristics with the mutation profiles in 50 patients with advanced gastric cancer (AGC). Among the 35 hotspot genes and 19 genes for copy number variations (CNVs), 18 single nucleotide variants (SNVs) or small insertions and deletions (14 missense and four frameshift mutations), and 10 amplifications were identified. To examine the association between mutation profiles and clinicopathological characteristics, each element of the clinicopathological characteristics was categorized into three groups: No alteration, PI3K catalytic subunit α (PIK3CA) alterations and alterations other than PIK3CA. Fisher's exact test identified no statistical differences between the clinicopathological characteristics, with the exception of the Tumor-Node-Metastasis (TNM) T stage between the three groups. Cases of AGC with somatic alterations but no PIK3CA exhibited a significant difference in the TNM T stage compared with those with no alterations or PIK3CA alterations (P=0.044). In addition, AGC with PIK3CA alterations was categorized by Lauren's classification to the intestinal type only. The distribution of Lauren's classification in AGC with PIK3CA alterations was statistically different compared with AGC with alterations other than PIK3CA (P=0.028), but not compared with AGC with no alterations (P=0.076). In conclusion, the present study demonstrated a molecular profiling approach that identified potential molecular classifications for gastric cancer and suggested a framework for precision medicine in AGC.

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Clinicopathological Significance of Elevated PIK3CA Expression in Gastric Cancer

Cited by 15 publications

References 27 publications

Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

Association between PIK3CA alteration and prognosis of gastric cancer patients: a meta-analysis

Genetic profiling of somatic alterations by Oncomine Focus Assay in Korean patients with advanced gastric cancer

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