Relationships between PIK3CA gene status and clinical features and prognosis in triple-negative breast cancer / 国际肿瘤学杂志

Objective:To detect the status of PIK3CA in triple-negative breast cancer (TNBC) , and to analyze the relationships between PIK3CA mutation and clinical features and its impact on prognosis.Methods:From January 1, 2016 to December 31, 2018, 50 patients with primary TNBC admitted to Xinxiang Central Hospital of Henan Province were collected. The PIK3CA mutation status was detected, and the relationships between PIK3CA mutation and clinical characteristics of patients with TNBC and its impact on prognosis were analyzed.Results:PIK3CA gene mutation was detected in 9 of 50 TNBC patients, with a mutation frequency of 18.0%. H1047R mutation was found in 4 cases, E545K mutation in 3 cases and E542K mutation in 2 cases. PIK3CA gene mutation was not associated with age ( χ2=3.55, P=0.060) , tumor location ( χ2=1.01, P=0.315) , tumor size ( χ2<0.01, P>0.999) , lymph node status ( χ2=0.76, P=0.385) , clinical stage ( χ2=0.65, P=0.420) , Ki-67 value ( χ2<0.01, P>0.999) , P53 status ( χ2=0.02, P=0.894) and human epidermal growth factor receptor-2 (HER-2) status ( χ2=1.65, P=0.200) . Prognostic analysis showed that 3-year disease-free survival rates of wild-type PIK3CA patients was significantly higher than that of mutant PIK3CA patients (80.5% vs. 11.1%, χ2=28.23, P<0.001) . Conclusion:The frequency of PIK3CA gene mutation is higher in TNBC patients. There is no correlation between PIK3CA mutation and clinicopathologic features in TNBC patients. PIK3CA gene mutation may be significantly associated with poor prognosis of TNBC patients.

Views on the Current Diagnosis and Treatment of PIK3CA-Related Overgrowth Spectrum / 罕见病研究

PIK3CA-related overgrowth spectrum (PROS) is a rare condition characterized by disproportionate overgrowth of head, neck, trunk, or extremity, caused by PIK3CA gene mutation. This condition has negative impact on the physical appearance, functions, and psychosocial well-being of the patients. The condition causes social and economic burden, too. The gold standard for the diagnosis of PROS is the genetic testing using somatic tissue, but detecting low-level mosaic mutations of PIK3CA gene remains a challenge. There is no specific treatment now. Supportive management including surgery and other interventions have limited effects in improving cosmetic outcome and functions. Multidisciplinary collaboration is the key to the success of managing PROS. Targeted gene therapy is promising in improving the outcome for patients with severe PROS. Patients diagnosed with negative genetics test by the clinical measures are often ineligible for novel gene therapy. This article reviews the clinical manifestations, diagnosis, and treatments of PROS, aiming to improve the current understanding of this rare condition.

BRAF/ KRAS and PIK3CA mutation characteristics and clinical significance in primary small cell lung caner / 中华放射肿瘤学杂志

Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95％CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95％CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.

The correlation of PIK3CA gene mutation and the efficacy of anti-HER2 targeted therapy for breast cancer / 国际肿瘤学杂志

It has been shown that the PIK3CA mutation in HER2 positive breast cancer is up to 25%, and thus activates PI3K-Akt signaling pathway,promotes HER2 mediated tumor cell epithelial transformation, alters the intrinsic phenotype of HER2 overexpression breast cancer,and finally leads to resistance to anti HER2 targeted therapy.Some studies have shown that the PIK3CA gene mutation is associated with the efficacy of anti-HER2 targeted therapy.Therefore,real-time monitoring of PIK3CA gene mutation will promote indivi-dualized anti-HER2 targeted therapy.

A functional variant at miR-520a binding site in PIK3CA alters susceptibility to colorectal cancer in a Chinese Han population / 中国癌症杂志

Background and purpose: Increasing evidence has indicated that polymorphisms in the microRNA (miRNA, miR) binding site of target gene can alter the ability of miRNA and modulate the risk of cancer. We aimed to investigate the association between a miR-520a binding site single nucleotide polymorphism (SNP) rs141178472 in the PIK3CA 3’UTR and the risk of colorectal cancer in a Chinese Han population. Methods:The polymorphism rs141178472 was analyzed in a case-control study, including 386 colorectal cancer patients and 394 age-and sex-matched controls. The relationship between the polymorphism and the risk of colorectal cancer was examined by statistical methods. Results:Individuals carrying the rs141178472 CC genotype or C allele had an increased risk of developing colorectal cancer (CC vs TT, OR=1.716, 95%CI:1.084-2.716, P=0.022;C vs T, OR=1.258, 95%CI:1.021-1.551, P=0.033). Furthermore, the expression of PIK3CA was detected in the peripheral blood mononucleated cell of colorectal cancer patients, suggesting that mRNA levels of PIK3CA might be associated with SNP rs141178472. Conclusion:These ifndings provide evidence that a miR-520a binding site polymorphism rs141178472 in the PIK3CA 3’UTR may play crucial roles in the etiology of colorectal cancer.

Analysis of transfection characteristic of two different fluorescently labeled siRNA targeting PIK3CA gene in vitro / 中国基层医药

Objective To compare transfection properties of two different fluorescently labeled PIK3CA siR-NA and to screen out PIK3CA siRNA with high transfection efficiency and strong anti-quenching ability.Methods Two different fluorescently labeled PIK3CA siRNA was transfected into gastric cancer cell BGC-823 by Lipofectamine 2000.The distribution and quenching of fluorescence were observed by inverted fluorescence microscope.Image J software was used to analyze their transfection efficiency.Real-time quantitative PCR was performed to detect the effect of different fluorescently labeled PIK3CA siRNA on PIK3CA mRNA expression.Results The transfection efficiency and anti-quenching ability of two different fluorescently labeled PIK3CA siRNA were different under the same transfection conditions.The transfection efficiency showed no significant differences between Cy3 or FAM labeled PIK3CA siRNA and negative control siRNA(P ＞ 0.05),but the transfection efficiency of Cy3 labeled PIK3CA siRNA and negative control siRNA was significantly higher than the FAM labeled (P ＜ 0.05).Inhibitory efficacy of target mRNA expression induced by Cy3 labeled PIK3CA siRNA was significantly higher than that of FAM labeled PIK3CA siRNA.Conclusion Cy3 labeled PIK3CA siRNA could act as a good tracer and provide an important evidence for further construction of Cy3 labeled PIK3CA siRNA nanoparticle.