Globular C1q Receptor (gC1qR/p32/HABP1) Is Overexpressed in Malignant Pleural Mesothelioma and Is Associated With Increased Survival in Surgical Patients Treated With Chemotherapy

Our plain-English summary of Globular C1q Receptor (gC1qR/p32/HABP1) Is Overexpressed in Malignant Pleural Mesothelioma and Is Associated With Increased Survival in Surgical Patients Treated With Chemotherapy, by X. Li, T. Eguchi, R.G. Aly, et al (Frontiers in Oncology, 2019).

The study

• Authors: X. Li, T. Eguchi, R.G. Aly, N.K. Chintala, K.S. Tan, M.G. Zauderer, F.R. Dembitzer, M.B. Beasley, B. Ghebrehiwet, P.S. Adusumilli, E.I.B. Peerschke
• Journal: Frontiers in Oncology
• Published: 2019;9:1042
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Globular C1q receptor (gC1qR/p32/HABP1) is overexpressed in a variety of cancers, particularly adenocarcinomas. This study investigated gC1qR expression in malignant pleural mesothelioma (MPM) and its pathophysiologic correlates in a surgical patient cohort. Methods: Tissue microarrays comprising 6 tumoral and 3 stromal cores from 265 patients with MPM (216 epithelioid, 26 biphasic, and 23 sarcomatoid; 1989-2010) were investigated by immunohistochemistry for gC1qR expression (intensity and distribution by H-score, range 0-300), and immune cell infiltration. Overall survival (OS) was analyzed by the Kaplan-Meier method (high vs. low gC1qR expression delineated by median score) in the whole cohort and by neoadjuvant chemotherapy (NAC) status. Multivariable Cox analysis included stage, chemotherapy, and immune cell infiltration. Results: gC1qR was overexpressed in all histological types of MPMs (263/265, 99.2%) compared to normal pleura. In epithelioid MPM, high gC1qR expression was associated with better OS (median 25 vs. 11 months; p = 0.020) among NAC patients, and among patients without NAC (No-NAC) but who received post-operative chemotherapy (median OS 38 vs. 19 months; p = 0.0007). In multivariable analysis, high gC1qR expression was an independent factor for improved OS in patients treated with NAC. In the No-NAC cohort, high gC1qR expression correlated with lower tumor stage. Moreover, the influence of Ki67 and CD4 T-cell infiltration on OS were more pronounced among patients with high gC1qR expression. Conclusion: This is the first description of gC1qR expression in MPM. The data identify gC1qR as a potential new prognostic factor in patients treated with surgery and chemotherapy.

Copyright © 2019 Li, Eguchi, Aly, Chintala, Tan, Zauderer, Dembitzer, Beasley, Ghebrehiwet, Adusumilli and Peerschke.

In plain English

This retrospective study at Memorial Sloan Kettering Cancer Center, New York, examined tumor tissue from 265 surgical patients with malignant pleural mesothelioma diagnosed between 1989 and 2010. Of these, 216 tumors were epithelioid, 26 biphasic and 23 sarcomatoid. The authors stained the tissue for a protein called gC1qR and scored its amount. The study did not examine asbestos exposure as a cause. gC1qR was found in 263 of 265 tumors, at higher levels than in 6 normal pleura samples. Later analyses covered only epithelioid tumors. Among patients given chemotherapy before surgery, median survival was 25 months with high gC1qR and 11 months with low gC1qR (p = 0.020). Among patients not given chemotherapy before surgery but given it afterward, the figures were 38 and 19 months (p = 0.0007). Among patients who received chemotherapy neither before nor after surgery, the survival difference was not statistically significant (HR 0.82, p = 0.3663). The authors called the study exploratory and concluded that it supports further research on gC1qR as a potential new prognostic factor. They noted it included only surgical patients and used small tissue cores rather than whole tissue sections.

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: Retrospective study of stored tumor tissue (tissue microarrays stained by immunohistochemistry), with survival analysis in a surgical patient cohort
• Who was studied: 265 patients with malignant pleural mesothelioma treated surgically and diagnosed at Memorial Sloan Kettering Cancer Center, New York, 1989 to 2010: 216 epithelioid, 26 biphasic and 23 sarcomatoid. Of the epithelioid patients, 59 received chemotherapy before surgery and 157 did not. Normal pleura from 6 surgical patients served as controls.
• Exposure: Not an asbestos exposure study. The factor examined was the level of the protein gC1qR in tumor tissue, scored by staining intensity and the percentage of positive tumor cells (H-score, 0 to 300) and split into high or low at the median. Asbestos exposure history was recorded only as a patient characteristic.
• Main results:
  • gC1qR was found in 263 of 265 mesotheliomas (99.2%), across all histological types, and at higher levels than in normal pleura. Median H score was 156 for epithelioid tumors, 150 for non-epithelioid tumors and 30 for normal pleura.
  • Epithelioid patients who received chemotherapy before surgery: median overall survival was 25 months with high gC1qR and 11 months with low gC1qR (p = 0.020).
  • Epithelioid patients without chemotherapy before surgery but with chemotherapy after surgery: median overall survival was 38 months with high gC1qR and 19 months with low gC1qR (p = 0.0007).
  • Epithelioid patients who received chemotherapy neither before nor after surgery: gC1qR level did not significantly affect overall survival (HR 0.82, p = 0.3663).
  • In multivariable analysis, high gC1qR was an independent factor for better overall survival only in the group given chemotherapy before surgery (HR 0.54; 95% CI 0.30 to 0.96; p = 0.037).
  • In epithelioid patients without chemotherapy before surgery, higher gC1qR was associated with lower stage (p-Stage p = 0.040; T category p = 0.005). A similar trend in the chemotherapy-before-surgery group was not statistically significant.
  • In the no-chemotherapy-before-surgery group, among patients with high gC1qR, high versus low Ki-67 (a marker of tumor cell growth) was linked to much shorter survival (HR 5.31, p less than 0.001). Among patients with low gC1qR, there was no significant difference (HR 1.35, p = 0.219).
  • In the no-chemotherapy-before-surgery group, among patients with high gC1qR, high infiltration of CD4 T cells was associated with better survival (HR 0.43, p = 0.0007). This was not seen among patients with low gC1qR.
• The authors' conclusion: The authors concluded that gC1qR is overexpressed in all three histologic subtypes of mesothelioma. In epithelioid mesothelioma, they found it prognostic for better overall survival in patients who received chemotherapy before or after surgery. They described the study as exploratory and said its findings support further investigation of gC1qR as a potential new prognostic factor.
• Limitations the authors state:
  • Only surgical patients were studied, and tissue cores rather than whole tissue sections were assessed.
  • There were too few non-epithelioid cases, so the main analyses were limited to epithelioid tumors.
  • Treatment regimens varied, so patients were only broadly grouped by whether they received chemotherapy before surgery.
  • The authors stated that prospective studies are needed to understand whether gC1qR can identify patients likely to benefit from chemotherapy.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Chemotherapy, Adenocarcinoma, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Immunohistochemistry, Overall Survival.

Related studies

• Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma — E. Tolnay, C. Kuhnen, et al. (1998)
• Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy — A.P. Desai, F. Kosari, et al. (2023)
• gC1qR/HABP1/p32 Is a Potential New Therapeutic Target Against Mesothelioma — E. Peerschke, K. Stier, et al. (2020)
• Hyperthermic intrathoracic chemotherapy after cytoreductive surgery in malignant pleural mesothelioma: a single-center retrospective cohort study suggesting increased morbidity without survival benefit — N. Baldes, F. Doerr, et al. (2026)
• Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection — D.J. Sugarbaker, R.R. Gill, et al. (2013)
• Surgical management of malignant pleural mesothelioma: impact of surgery on survival and quality of life-relation to chemotherapy, radiotherapy, and alternative therapies — S. Papaspyros, S. Papaspyros (2014)

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