TY - JOUR
T1 - Globular C1q Receptor (gC1qR/p32/HABP1) Is Overexpressed in Malignant Pleural Mesothelioma and Is Associated With Increased Survival in Surgical Patients Treated With Chemotherapy
AU - Li, Xiaoyu
AU - Eguchi, Takashi
AU - Aly, Rania G.
AU - Chintala, Navin K.
AU - Tan, Kay See
AU - Zauderer, Marjorie G.
AU - Dembitzer, Francine R.
AU - Beasley, Mary Beth
AU - Ghebrehiwet, Berhane
AU - Adusumilli, Prasad S.
AU - Peerschke, Ellinor I.B.
N1 - Funding Information:
We thank David B. Sewell of the MSK Thoracic Surgery Service for their editorial assistance. Funding. The authors' laboratory work was supported by grants from the National Institutes of Health (P30 CA008748, R01 CA236615-01, and R01 CA235667), the U.S. Department of Defense (CA170630, BC132124, LC160212, and CA180889), the Mesothelioma Foundation (Award # 549976, Craig Kozicki Memorial grant), and the Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center.
Publisher Copyright:
© Copyright © 2019 Li, Eguchi, Aly, Chintala, Tan, Zauderer, Dembitzer, Beasley, Ghebrehiwet, Adusumilli and Peerschke.
PY - 2019/10/11
Y1 - 2019/10/11
N2 - 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.
AB - 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.
KW - CD4 T cell
KW - chemotherapy
KW - complement system
KW - gC1qR/p32/HABP1 (gC1qR)
KW - malignant pleural mesothelioma
UR - http://www.scopus.com/inward/record.url?scp=85074268001&partnerID=8YFLogxK
U2 - 10.3389/fonc.2019.01042
DO - 10.3389/fonc.2019.01042
M3 - Article
AN - SCOPUS:85074268001
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
M1 - 1042
ER -