Wnt7A is a putative prognostic and chemosensitivity marker in human malignant pleural mesothelioma

Our plain-English summary of Wnt7A is a putative prognostic and chemosensitivity marker in human malignant pleural mesothelioma, by T. Hirata, Q. Zheng, Z. Chen, et al (Oncology Reports, 2015).

The study

• Authors: T. Hirata, Q. Zheng, Z. Chen, H. Kinoshita, J. Okamoto, J. Kratz, H. Li, N. Lui, H. Do, T. Cheng, H.H. Tseng, K. Koizumi, K. Shimizu, H.M. Zhou, D. Jablons, B. He
• Journal: Oncology Reports
• Published: 2015;33(4):2052-60
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a poor prognosis, limited treatment options, and a worldwide incidence that is expected to increase in the next decade. We evaluated Wnt7A expression in 50 surgically resected tumor specimens using quantitative PCR. The expression values, were assessed by clinicopathological factors and K-M and Cox's regression with OS. The mean level of Wnt7A expression had a significant correlation with International Mesothelioma Interest Group (IMIG) stage (P<0.034), gender, smoking history and ethnicity, respectively (P=0.020, P=0.014, P=0.039). In the univariate analysis, low Wnt7A expression was a significant negative factor for overall survival (P=0.043, HR=2.30). However, multivariate Cox's regression revealed no significant factors for overall survival (low Wnt7A: P=0.051, HR=2.283; non-epithelioid subtype: P=0.050, HR=2.898). In patients with epithelioid tumors, those with low Wnt7A expression had significantly worse prognosis (P=0.019, HR=2.98). In patients with epithelioid tumors, females had significantly better prognosis than males (P=0.035). In patients who did not have neoadjuvant chemotherapy, prognosis was significantly more favorable for patients with high Wnt7A expression than for those with low Wnt7A expression (P=0.031). Among the patients with low Wnt7A-expressing tumors, those who received neoadjuvant chemotherapy had better prognosis than those who did not (P=0.024). The results of our study suggest that Wnt7A expression is a putative prognostic factor and a predictor of chemosensitivity.

In plain English

This study, from the University of California, San Francisco, measured activity of a gene called Wnt7A in tumor tissue from 50 patients who had surgery for malignant pleural mesothelioma between 1999 and 2005. The article did not measure asbestos exposure. Patients were split into high (30) and low (20) Wnt7A groups. In a single-factor analysis, median overall survival was 26.7 months with high Wnt7A versus 11.8 months with low (P=0.043); the hazard ratio for low compared with high Wnt7A was 2.30 (95% CI 1.01 to 5.25). In the combined analysis, neither low Wnt7A (P=0.051) nor non-epithelioid subtype (P=0.05) was statistically significant. Among 42 patients with epithelioid tumors, low Wnt7A was linked to worse survival (P=0.019). In that epithelioid group, patients with low-Wnt7A tumors who had chemotherapy before surgery survived longer than those without it (P=0.024). All 9 women had high Wnt7A. The authors concluded that Wnt7A is a putative prognostic factor and a possible predictor of benefit from pre-surgery chemotherapy. They noted performance status data were missing for more than half the patients. The article's numbers contain several internal inconsistencies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory gene-expression study of stored surgical tumor samples, with survival analysis of the patients they came from (consecutive surgical patients at one center)
• Who was studied: 50 consecutive patients with malignant pleural mesothelioma (MPM) who had surgical resection at the University of California, San Francisco, between 1999 and 2005. 24 had neoadjuvant chemotherapy before surgery. 41 were men and 9 were women. 42 had epithelioid tumors.
• Exposure: Not an asbestos exposure study. The factor studied was Wnt7A gene expression in tumor tissue, measured by quantitative real-time RT-PCR and compared with pooled normal pleural tissue. Neoadjuvant chemotherapy was also examined.
• Main results:
  • All 50 patients: overall survival was longer with high Wnt7A expression than with low expression (26.7±11.1 months vs. 11.8±4.9; P=0.043). Table I labels these figures as median overall survival time.
  • Univariate analysis, all patients: low Wnt7A expression was associated with worse overall survival. The hazard ratio for low compared with high Wnt7A was 2.30 (95% CI 1.01-5.25), P=0.043.
  • Multivariate analysis: no factor was statistically significant for overall survival. Low Wnt7A had P=0.051, HR=2.283 (95% CI 0.998 to 5.22). Non-epithelioid subtype had P=0.05, HR=2.898 (95% CI 0.998 to 8.416).
  • 42 patients with epithelioid tumors: median survival was 25 months (95% CI 8.8 to 41.2) with high Wnt7A versus 10.4 months (95% CI 5.2 to 15.6) with low Wnt7A. The difference was reported as significant (P=0.019).
  • Patients with low Wnt7A epithelioid tumors: overall survival was better in those who had neoadjuvant chemotherapy than in those who did not (P=0.024; HR=4.31, 95% CI 1.1 to 16.9).
  • Patients with high Wnt7A epithelioid tumors: overall survival did not differ by neoadjuvant chemotherapy (P=0.902).
  • Among the 20 patients who received neoadjuvant chemotherapy, survival did not differ significantly between low and high Wnt7A tumors (P=0.425). Among the 22 who did not, survival was better with high Wnt7A tumors (P=0.031).
  • All 9 female patients had high Wnt7A expression (Table I: high group 21 men and 9 women; low group 20 men and 0 women; P=0.007).
  • Wnt7A expression differed between 11 paired normal and tumor tissues (P=0.005), and by tumor stage, gender, smoking status and ethnicity. Patients with a smoking history had lower Wnt7A expression.
• The authors' conclusion: The authors concluded that Wnt7A is a putative novel prognostic factor for MPM and a novel predictor of whether neoadjuvant chemotherapy will be beneficial. They suggested it is possibly a tumor-suppressor gene in MPM. In their discussion they wrote that they recommend neoadjuvant chemotherapy for patients with low Wnt7A tumors.
• Limitations the authors state:
  • Performance status data were missing for more than half the patients, so its contribution to prognosis could not be compared with that of Wnt7A.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Mesothelioma, IMIG, Overall Survival, Non-epithelioid, Epithelioid, Neoadjuvant Chemotherapy.

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