MTAP is an independent prognosis marker and the concordant loss of MTAP and p16 expression predicts short survival in non-small cell lung cancer patients

Su, Cheng-Tau; Chang, Yuan‐Shiun; Chan, Yin-Ching; Lin, Tsung-Chieh; Huang, Ming‐Shyan; Yang, Chih‐Jen; Hsiao, Michael

doi:10.1016/j.ejso.2014.04.017

Cited by 38 publications

(33 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that a loss of MTAP expression sensitizes cancer cells to DNSP inhibitors, as shown in studies on leukemia and lung cell lines [30] and various malignant neoplasms [27] . This is particularly relevant for lymphomas, leukemias [27,29] and nonsmall-cell lung carcinoma [34,45] . Nevertheless, chemotherapy regimens with pemetrexed were not effective for pediatric patients with medulloblastomas, ependymomas and high-grade gliomas [49] , and the addition of methotrexate in the chemotherapeutic treatment of infratentorial ependymomas did not improve the response to these drugs [50] .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

et al. 2015

View full text Add to dashboard Cite

Background/Objectives: Pilocytic astrocytomas (PAs) are the most frequent astrocytomas in children and adolescents. Methilthioadenosine phosphorylase(MTAP) is a tumor-suppressor gene, the loss of expression of which is associated with a poor prognosis and better response to specific chemotherapy in leukemia and non-small-cell lung cancer. The expression of MTAP in brain tumors remains largely unknown and its biological role in PA is still unexplored. Our aims were to describe the immunohistochemical MTAP expression in a series of PAs and relate it to the clinicopathological features of the patients. Methods: We assessed MTAP expression on immunohistochemistry in 69 pediatric and adult patients with PA in a tissue microarray platform. Results: Retained expression of MTAP was seen in >85% of the tumors compared to in the nonneoplastic adjacent tissue. Only 3 supratentorial tumors showed a complete loss of MTAP expression. No significant association with clinicopathological features or overall survival of the patients was found. Conclusions: MTAP expression is retained in PAs and is not an outcome predictor for these tumors. Nevertheless, a subset of patients with PAs exhibiting a loss of MTAP could potentially benefit from treatment with specific chemotherapy, especially when lesions are recurrent or surgical resection is not recommended.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In contrast, the loss of expression of the neighbor gene p16 has a prognostic impact on PAs [19] . Recently, it was described that the simultaneous loss of expression of p16 and MTAP determines shorter survival of patients with non-small-cell lung cancer [45] .…”

Section: Discussionmentioning

confidence: 99%

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

et al. 2015

View full text Add to dashboard Cite

show abstract

“…It was reported that MTAP had a broad expression profile in the mammalian and was a key enzyme in the methionine salvage pathway 24,37. Loss of MTAP expression can exert a tumor promoting effect, suggesting that MTAP may function as a tumor suppressor gene 21,30,31,38. Moreover, the genetic polymorphism of MTAP was also considered as one of the potential genetic factors in various tumors 29,39-41.…”

Section: Discussionmentioning

confidence: 99%

Association of common variants in MTAP with susceptibility and overall survival of osteosarcoma: a two-stage population-based study in Han Chinese

Zhi

Liú²,

et al. 2016

J. Cancer

View full text Add to dashboard Cite

Osteosarcoma (OS) is a common malignant tumor, which exists widely in the bone of children and adolescents, and genetic factors may influence its susceptibility. Recently, the gene MTAP has been reported to be associated with OS in a Caucasian population. To investigate the association of common variants in MTAP with OS risk in Han Chinese individuals, we designed a two-stage case-control study with 392 OS patients and 1,578 unrelated healthy controls of Han Chinese individuals. A total of 17 tagging single nucleotide polymorphisms (SNPs) were firstly genotyped in the discovery stage, and single-SNP association and haplotypic association analyses have been performed. The SNP rs7023329 was found to be strongly associated with the OS risk (adjusted P = 0.002908), and the results of odds ratios (ORs) and 95% confidence intervals (CI) revealed increased risks from A allele of the SNP on OS (OR=1.33, 95% CI=1.13-1.62). The results were confirmed with a similar pattern in the validation stage (adjusted P = 0.006737, OR=1.49, 95% CI=1.11-2.00). Moreover, haplotypic analyses indicated that one haplotype block containing rs7023329 was significantly associated with OS risk in both stages (both global P<0.0001). The statistically significant association between the rs7023329 genotype and poor survival in OS patients was also observed. To sum up, our results prove that MTAP plays an important role in the etiology of OS, suggesting this gene as a potential genetic modifier for OS development.

show abstract

“…However, our survival analysis indicates that TP16 positivity is associated with longer survival in NSCLC. Although TP16 may be a prognostic indicator in NSCLC patients, controversy regarding geographical differences as well as differences in tissue types still exist (32). The present study provides new possibilities in the prognosis and diagnosis of advanced NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Involvement of TP53 and TP16 expression in human papillomavirus-associated non-small cell lung cancer

Zhang

Deng

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Human papilloma virus (HPV) infection has previously been reported to be associated with TP53 and TP16 expression in Japanese and Taiwanese patients with lung cancer, but data for advanced non-small cell lung cancer (NSCLC) patients is limited. The present study examined the association between HPV infection and TP53 and TP16 expression in Chinese patients with advanced NSCLC. HPV DNA was detected in 20 out of 83 (24%) lung tumors, and was observed more frequently in non-smokers, patients with lymph node metastasis, and patients with poorly differentiated tumors (P=0.048, P=0.044 and P=0.024, respectively). Thirteen (65%) out of 20 HPV-infected tumors were positive for TP53 expression while eight (40%) were positive for TP16 expression. Multivariate analysis revealed that poor differentiation alone (OR=0.163) was an independent predictive factor of HPV infection in NSCLC. TP16-positive patients had a significantly longer survival time when compared with TP16-negative patients (P<0.001, log-rank test), a trend a not observed for TP53. Our results suggest that TP53 and TP16 protein expression is not associated with the expression of HPV DNA, but that TP16 expression may be an independent prognostic factor of long survival in advanced NSCLC.

show abstract

MTAP is an independent prognosis marker and the concordant loss of MTAP and p16 expression predicts short survival in non-small cell lung cancer patients

Cited by 38 publications

References 25 publications

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

Association of common variants in MTAP with susceptibility and overall survival of osteosarcoma: a two-stage population-based study in Han Chinese

Involvement of TP53 and TP16 expression in human papillomavirus-associated non-small cell lung cancer

Contact Info

Product

Resources

About