Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence

被引:7
作者
Hoefsmit, Esmee P. [1 ]
Vollmy, Franziska [2 ,3 ]
Rozeman, Elisa A. [4 ]
Reijers, Irene L. M. [4 ]
Versluis, Judith M. [4 ]
Hoekman, Liesbeth [5 ]
van Akkooi, Alexander C. J. [6 ,7 ,8 ]
Long, Georgina, V [6 ,7 ,9 ,10 ]
Schadendorf, Dirk [11 ,12 ]
Dummer, Reinhard [13 ]
Altelaar, Maarten [2 ,3 ,5 ]
Blank, Christian U. [1 ,4 ,14 ]
机构
[1] Netherlands Canc Inst, Dept Mol Oncol & Immunol, Amsterdam, Netherlands
[2] Univ Utrecht, Ctr Biomol Res, Biomol Mass Spectrometry & Prote, Utrecht, Netherlands
[3] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands
[4] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands
[5] Netherlands Canc Inst, Prote Facil, Amsterdam, Netherlands
[6] Univ Sydney, Melanoma Inst Australia, Sydney, NSW, Australia
[7] Univ Sydney, Fac Med & Hlth, Sydney, NSW, Australia
[8] Royal Prince Alfred Hosp, Dept Melanoma & Surg Oncol, Sydney, NSW, Australia
[9] Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia
[10] Royal North Shore & Mater Hosp, Dept Med Oncol, Sydney, NSW, Australia
[11] Univ Hosp Essen, Dept Dermatol, Essen, Germany
[12] Germany Canc Consortium, Partner Site Essen, Essen, Germany
[13] Univ Zurich, Univ Hosp Zurich, Dept Dermatol, Zurich, Switzerland
[14] Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands
来源
CANCER RESEARCH COMMUNICATIONS | 2023年 / 3卷 / 04期
基金
欧盟地平线“2020”;
关键词
LEUCINE-RICH ALPHA-2-GLYCOPROTEIN; COLORECTAL-CANCER; PROMOTES ANGIOGENESIS; COMBINED NIVOLUMAB; PROGNOSTIC MARKER; POOLED ANALYSIS; SERUM-LEVELS; SURVIVAL; GROWTH; BIOMARKER;
D O I
10.1158/2767-9764.CRC-23-0015
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum samples of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired samples of patients with stage III that progressed to stage IV disease (n = 64) was used to identify markers associated with higher tumor burden. Baseline patient samples from the OpACIN-neo study (n = 83) and PRADO study (n = 49; NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with pro- gressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Espe- cially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event- free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB.Significance: LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up. When comparing baseline proteins overlapping between patients with pro- gressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Espe- cially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event- free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB.Significance: LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up.
引用
收藏
页码:672 / 683
页数:12
相关论文
共 50 条
[41]   Preoperative anemia is associated with disease recurrence and progression in patients with non-muscle-invasive bladder cancer [J].
Soria, Francesco ;
Moschini, Marco ;
Abufaraj, Mohammad ;
Wirth, Gregory J. ;
Foerster, Beat ;
Gust, Kilian M. ;
Oezsoy, Mehmet ;
Briganti, Alberto ;
Gontero, Paolo ;
Mathieu, Romain ;
Roupret, Morgan ;
Karakiewicz, Pierre I. ;
Shariat, Shahrokh F. .
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 2017, 35 (03) :113.e9-113.e14
[42]   Recent Advances in Predicting Mortality and Progression of Systemic Sclerosis-Associated Interstitial Lung Disease [J].
Park, Moo Suk .
TUBERCULOSIS AND RESPIRATORY DISEASES, 2020, 83 (04) :326-328
[43]   Can Recurrence and Progression be Predicted by HYAL-1 Expression in Primary T1 Bladder Cancer? [J].
Mammadov, Elnur ;
Aslan, Guven ;
Tuna, Burcin ;
Bozkurt, Ozan ;
Yorukoglu, Kutsal .
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 2014, 15 (23) :10401-10405
[44]   Increased Expression of Fibulin-1 Is Associated With Hepatocellular Carcinoma Progression by Regulating the Notch Signaling Pathway [J].
Gong, Jiao ;
Jie, Yusheng ;
Xiao, Cuicui ;
Zhou, Wenying ;
Li, Xinhua ;
Chen, Yaqiong ;
Wu, Yuankai ;
Cao, Jing ;
Zhang, Qi ;
Gao, Zhiliang ;
Hu, Bo ;
Chong, Yutian .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2020, 8
[45]   New insight into the role of ANXA1 in melanoma progression: involvement of stromal expression in dissemination [J].
Delorme, Solene ;
Privat, Maud ;
Sonnier, Nicolas ;
Rouanet, Jacques ;
Witkowski, Tiffany ;
Kossai, Myriam ;
Mishellany, Florence ;
Radosevic-Robin, Nina ;
Juban, Gaetan ;
Molnar, Ioana ;
Quintana, Mercedes ;
Degoul, Francoise .
AMERICAN JOURNAL OF CANCER RESEARCH, 2021, 11 (04) :1600-+
[46]   Angiotropism in primary cutaneous melanoma is associated with disease progression and distant metastases: A retrospective study of 179 cases [J].
Moy, Andrea P. ;
Duncan, Lyn M. ;
Muzikansky, Alona ;
Kraft, Stefan .
JOURNAL OF CUTANEOUS PATHOLOGY, 2019, 46 (07) :498-507
[47]   Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma [J].
Nakashima, Chie ;
Yamamoto, Kazuhiko ;
Fujiwara-Tani, Rina ;
Luo, Yi ;
Matsushima, Sayako ;
Fujii, Kiyomu ;
Ohmori, Hitoshi ;
Sasahira, Tomonori ;
Sasaki, Takamitsu ;
Kitadai, Yasuhiko ;
Kirita, Tadaaki ;
Kuniyasu, Hiroki .
CANCER SCIENCE, 2018, 109 (06) :2036-2045
[48]   Tumor CD155 Expression Is Associated with Resistance to Anti-PD1 Immunotherapy in Metastatic Melanoma [J].
Lepletier, Ailin ;
Madore, Jason ;
O'Donnell, Jake S. ;
Johnston, Rebecca L. ;
Li, Xian-Yang ;
McDonald, Elizabeth ;
Ahern, Elizabeth ;
Kuchel, Anna ;
Eastgate, Melissa ;
Pearson, Sally-Ann ;
Mallardo, Domenico ;
Ascierto, Paolo A. ;
Massi, Daniela ;
Merelli, Barbara ;
Mandala, Mario ;
Wilmott, James S. ;
Menzies, Alexander M. ;
Leduc, Charles ;
Stagg, John ;
Routy, Bertrand ;
Long, Georgina, V ;
Scolyer, Richard A. ;
Bald, Tobias ;
Waddell, Nicola ;
Dougall, William C. ;
Teng, Michele W. L. ;
Smyth, Mark J. .
CLINICAL CANCER RESEARCH, 2020, 26 (14) :3671-3681
[49]   High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality [J].
Athanasios, Tampakis ;
Ekaterini-Christina, Tampaki ;
Afrodite, Nonni ;
Ioannis, Kostakis D. ;
Alberto, Posabella ;
Konstantinos, Kontzoglou ;
Markus, von Flue ;
Evangelos, Felekouras ;
Gregory, Kouraklis ;
Nikolaos, Nikiteas .
BMC CANCER, 2021, 21 (01)
[50]   High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality [J].
Athanasios Tampakis ;
Ekaterini-Christina Tampaki ;
Afrodite Nonni ;
Ioannis D. Kostakis ;
Alberto Posabella ;
Konstantinos Kontzoglou ;
Markus von Flüe ;
Evangelos Felekouras ;
Gregory Kouraklis ;
Nikolaos Nikiteas .
BMC Cancer, 21