High levels of Phosphatase and Tensin Homolog Expression Predict Favorable Prognosis in Patients with Non-small Cell Lung Cancer

Abstract

The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 vs. 12.9 months, log rank P = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 vs. 15.54 months, log rank P = 0.043). High levels of PTEN expression resulted in 43 % reduction in risk for all NSCLC patients (HR 0.57, 95 % CI 0.33-0.98, P = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex, and tumor type (HR 0.56, 95 % CI 0.32-0.99; P = 0.048; HR 0.54, 95 % CI 0.36-0.97; P = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (P > 0.17). When levels of PTEN expression were binarized using the optimal cut-point, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80 and 58 %, respectively, P = 0.049) and in patients with AC than in those with squamous-cell carcinoma (78 and 58 %, respectively, P = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (P > 0.28). Our results suggest that high levels of PTEN expression may be favorable prognostic markers in NSCLC patients.

PTEN expression is a prognostic marker for patients with non-small cell lung cancer: a systematic review and meta-analysis of the literature

“…In our meta-analysis, the results from analyzing both the univariate and multivariate subgroups indicated that decreased expression of PTEN was associated with poor OS in patients with NSCLC. However, multivariate analysis ruled out the compounding effects from other clinicopathological factors such as sex, age, tumor size, nodal status and stage, among others [ 16 , 19 , 28 , 32 , 34 ]. Thus, according to the pooled result from analyzing the multivariate analysis subgroup, expression of PTEN may be considered to be an independent factor of poor prognosis in NSCLC patients.…”

“…While many histopathology research studies reported that PTEN downregulation correlates with unfavorable survival prognosis in NSCLC patients [ 13 – 16 ], some studies reached the opposite conclusion [ 17 , 18 ]. Therefore results in this field seem to be inconsistent.…”

PTENInhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/hTERTPathway in Lung Adenocarcinoma A549 Cells

“…In organisms, the biological functions of oncogenes and antioncogenes mutually antagonize each other to regulate cell proliferation, differentiation, apoptosis, cell cycle, and angiogenesis. It has been found that dozens of genes are closely correlated with lung cancer, among which the oncogene PTEN (phosphatase and tensin homolog) and the tumor suppressor hTERT (human telomerase reverse transcriptase) have been extensively studied in the past few years [1–4]. …”

Loss of phosphatase and tensin homolog expression correlates with clinicopathological features of non‐small cell lung cancer patients and its impact on survival: A systematic review and meta‐analysis

“…Only one study was a multinational study undertaken in 30 different countries, while the other 18 studies were single‐center studies (14 in Asian countries and 4 in Western countries) . NSCLC trials included either all histological subtypes ( n = 17), or adenocarcinoma (ADC) ( n = 2) . Data related to local advanced disease (stages I–III) comprised three of the 19 NSCLC trials, while 13 studies dealt with any stage (I–IV) .…”

“…All articles, including 2486 patients, listed the relationship between PTEN expression and survival outcome in NSCLC . The combined HR was 0.51 (95% CI 0.42–0.62; P = 0.000, I 2 = 59.5%) for OS in 16 studies (Fig ), but was 0.82 (95% CI 0.26–2.60; P = 0.733, I 2 = 84.7%) for DFS in three studies (Fig ; Table ) .…”