Programmed Death-Ligand 1 (PD-L1) Positivity and Factors Associated with Poor Prognosis in Patients with Gastric Cancer: An Umbrella Meta-Analysis

Gashaw Hassen; Amita Kasar; Nidhi Jain; Shivankshi Berry; Jhanvi Dave; Michlene Zouetr; V Lakshmi N Priyanka Ganapathiraju; Tejaswini Kurapati; Stephanie Oshai; Mohamed Saad; Jahangirkhan Pathan; Sheetal Kamat; Raghavendra Tirupathi; Urvish K Patel; Rishabh K Rana

doi:10.7759/cureus.23845

Programmed Death-Ligand 1 (PD-L1) Positivity and Factors Associated with Poor Prognosis in Patients with Gastric Cancer: An Umbrella Meta-Analysis

Cureus. 2022 Apr 5;14(4):e23845. doi: 10.7759/cureus.23845. eCollection 2022 Apr.

Authors

Gashaw Hassen^{1

2

3}, Amita Kasar⁴, Nidhi Jain^{5

6

7}, Shivankshi Berry^{8

9}, Jhanvi Dave¹⁰, Michlene Zouetr¹¹, V Lakshmi N Priyanka Ganapathiraju¹², Tejaswini Kurapati¹³, Stephanie Oshai¹⁴, Mohamed Saad¹⁵, Jahangirkhan Pathan¹⁶, Sheetal Kamat¹⁷, Raghavendra Tirupathi¹⁸, Urvish K Patel¹⁹, Rishabh K Rana²⁰

Affiliations

¹ Progressive Care, Mercy Medical Center, Baltimore, USA.
² Medicine and Surgery, Parma University, Parma, ITA.
³ Medicine, Addis Ababa University, Addis Ababa, ETH.
⁴ Internal Medicine, Krishna Institute of Medical Sciences, Secunderabad, IND.
⁵ Medicine and Surgery, Himalayan Institute of Medical Sciences, Dehradun, IND.
⁶ Hematology and Oncology, Brooklyn Cancer Care, Brooklyn, USA.
⁷ Internal Medicine, Sir Ganga Ram Hospital, New Delhi, IND.
⁸ Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, IND.
⁹ Internal Medicine, Nassau University Medical Center, New York, USA.
¹⁰ Internal Medicine, B.J. Medical College, Ahmedabad, IND.
¹¹ Family Medicine, American Institute of Antigua College of Medicine, St John's, ATG.
¹² Medicine and Surgery, Rangaraya Medical College, Kakinada, IND.
¹³ Medicine and Surgery, Narayana Medical College, Nellore, IND.
¹⁴ Medicine and Surgery, College of Medicine, University of Lagos, Lagos, NGA.
¹⁵ Gastroenterology, Theodor Bilharz Research Institute, Giza, EGY.
¹⁶ Internal Medicine, V. I. Vernadsky Crimean Federal University, Crimea, RUS.
¹⁷ Internal Medicine, Apollo Hospital, Bangalore, IND.
¹⁸ Internal Medicine, Keystone Health, Chambersburg, USA.
¹⁹ Public Health and Neurology, Icahn School of Medicine at Mount Sinai, New York, USA.
²⁰ Preventive and Social Medicine/Community Medicine, Shahid Nirmal Mahto Medical College, Dhanbad, Dhanbad, IND.

Abstract

Gastric cancer (GC) is one of the most common malignancies throughout the world with late diagnosis and poor prognosis. The expression of programmed death-ligand 1 (PD-L1) in GC is attributed to immune evasion and tumor progression. PD-L1 positivity has both predictive and prognostic biomarker potential. Aiming to summarize a large amount of research and to provide a definitive conclusion to the conflicting results on the prognostic significance of PD-L1 expression in GC, we performed an umbrella review based on existing meta-analyses which were published recently (2016-2021) and indexed in the PubMed database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used in August 2021 to screen articles, and data extraction with quality assessment was performed on the selected meta-analyses. Review Manager (RevMan) 5.3 software was used to analyze the HR and OR with a 95% confidence interval (CI) among PD-L1 positive GC patients. We also assessed the between-study heterogeneity (I ²). Forest and Funnel plots were obtained, and a P-value of <0.05 was considered statistically significant. A total of 567 articles were screened, and we selected three meta-analyses with a total of 40 studies conducted over a period of 14 years. In our umbrella review, a total of 8,419 GC patients with an average PD-L1 positivity of 39% were analyzed. We found that PD-L1 positivity in GC patients is associated with poor prognosis (pooled HR =1.44, 95% CI: 1.24-1.68, P<0.00001) having higher mortality reducing the chances of overall survival (OS). However, there are no significant differences in PD-L1 expression among different lymph node (LN) metastases (OR=1.31, 95% CI: 0.98-1.74, P=0.07) and tumor, node, and metastasis (TNM) stages (OR=1.13, 95% CI: 0.80-1.58, P=0.50). Early identification of PD-L1 expression may help tailor cost-effective and targeted immunotherapy among GC patients. More research is needed to further understand how PD-L1 affects LN metastasis and tumor invasion.

Keywords: clinicopathological; gastric cancer; hazard ratio; lymph node metastasis; meta-analysis; overall survival (os); pd-l1; poor prognosis; tumor stage; umbrella review.

Publication types

Review