Prognostic Value of TNFR2 and STAT3 among High-Grade Serous Ovarian Cancer Survivors According to Platinum Sensitivity.

Janisha Silva Raju,Ghofraan Abdulsalam Atallah,Nirmala Chandralega Kampan,Ravichandran Jeganathan,Chew Kah Teik,Nor Haslinda Abd Aziz,Reena Rahayu Md Zin,Muhammad Fakhri Mohd Saleh,Mohamad Nasir Shafiee

doi:10.3390/diagnostics11030526

Abstract

This study’s goal was to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in high-grade serous ovarian cancer (HGSC) tissues in relation to the platinum-based chemotherapy response and the prognosis outcome. A total of 25 HGSC patients underwent primary surgical debulking followed by first-line adjuvant platinum-based chemotherapy. Tissue microarray (TMA) slides were constructed utilising archived formalin fixed paraffin embedded (FFPE). The protein expression of TNFR2 and STAT3 were analysed using immunohistochemistry (IHC) staining and subsequently were correlated to the clinicopathological characteristics, platinum sensitivity as well as the duration of progression-free survival. About 14 out of 25 patients (56.0%) were platinum-sensitive. The progression free survival was significantly longer in the platinum-sensitive (PS) group when compared to those with the platinum-resistant group (PR), p = 0.0001. Among patients with TNFR2 strong expression on ovarian tissue, there was a significantly longer progression-free survival interval of 540 days in the PS group compared to PR, p = 0.0001. Patients with STAT3 expression also showed significantly better progression-free survival of 660 days in the PS group when compared to the PR group, p = 0.0001. In conclusion, patients with strong TNFR2 and STAT3 expression in the ovarian tissue had significantly longer progression-free survival interval in the PS group. Nevertheless, further research with a larger number of tissues may be required to demonstrate further significant differences.

Highlights

The American Cancer Society predicts that an estimated 21,750 new cases of ovarian cancer will be reported in 2020 and 13,940 people will suffer from ovarian cancer in the United States with just 48.6% having a 5-year survival rate [1]
As there are no specific clinical symptoms, epithelial ovarian cancer is generally diagnosed at an advanced stage in up to 75% of patients, and the commonest type is high-grade serous ovarian cancer (HGSC) [2]
Our aim is to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in tumour tissues collected from chemo-naïve patients diagnosed with high-grade serous ovarian carcinoma (HGSC) and to evaluate its association with platinum-based chemotherapy response and the prognosis outcome via progression-free survival

Summary

Introduction

The American Cancer Society predicts that an estimated 21,750 new cases of ovarian cancer will be reported in 2020 and 13,940 people will suffer from ovarian cancer in the United States with just 48.6% having a 5-year survival rate [1]. The standard of care for patients with HGSC consists of maximal cytoreductive surgery and platinum-based chemotherapy treatment [3]. Most of the patients (75%) reported HGSC at diagnosis experience a good initial response to optimal cytoreductive surgery followed by adjuvant platinum-based chemotherapy [4]. Up to 80% of HGSC patients establish tolerance to traditional chemotherapy leading to disease recurrence, posing a great challenge to subsequent chemotherapy choices [4,5]. The overall 10-year survival in HGSC following standard therapy is poor at only 30% [5]

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