Peritoneal fluid and serum levels of hepatocyte growth factor may predict the activity of endometriosis
Open accessAbstract
Background. The suitable parameter in PF as well as in serum that may predict the activity of endometriosis is not well described. Therefore, we tried to examine the peritoneal fluid (PF) and serum concentrations of hepatocyte growth factor (HGF) in different revised American Society of Reproductive Medicine (r‐ASRM) staging and morphologic appearances of endometriosis in an attempt to determine whether HGF can be clinically useful to predict the activity of pelvic endometriosis. Methods. Peritoneal fluid was collected from 137 women with endometriosis and 57 women without endometriosis during laparoscopy and blood sampling was collected from 37 women with endometriosis and 21 women without endometriosis before laparoscopy. The concentration of HGF in PF and serum was measured by enzyme‐linked immunosorbent assay. The ability of isolated macrophages and stroma to secrete HGF in response to lipopolysaccharide (LPS) was evaluated. Results. A significantly increased concentration of HGF in PF was found in women with endometriosis (1451.75±/90.7 pg/mL) than that in non‐endometriosis (1120.5±/77.3 pg/mL, p < /0.01) without any remarkable difference in HGF levels between women with stage I–/II endometriosis and stage III–/IV endometriosis. When we distributed serum and PF levels of HGF according to different color appearances of endometriosis, we found a significantly higher serum and PF levels of HGF in women containing dominant red peritoneal lesions in pelvic cavity (740±/109.3 pg/mL for serum; 1685±/183.4 pg/mL for PF) than those having other pigmented lesions (649±/79.5 pg/mL, p < /0.05 for serum; 1224±/67.8 pg/mL, p < /0.05 for PF) or chocolate cysts (485±/43.1 pg/mL, p < /0.05 for serum; 1118±/ 83.1 pg/mL, p < /0.01 for PF). Exogenous stimulation with LPS significantly increased the production of HGF in the culture media by macrophages and stroma derived from women with endometriosis than that in women without endometriosis. Conclusions. These results suggest that women with early or advanced endometriosis as measured by r‐ASRM scoring system are not associated with an increase in either serum or PF concentrations of HGF. Rather HGF levels in serum and PF were significantly increased in women harboring blood‐filled red peritoneal lesions and may be clinically useful to predict the activity of pelvic endometriosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HGF was suggested to be elevated in women with endometriosis, although this was not confirmed in an additional study.
“Hepatocyte growth factor (HGF) was suggested to be elevated in women with endometriosis [72], although this was not confirmed in an additional study [23, 73].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [73]
Cites
Revised American Society for Reproductive Medicine classification of endometriosis: 1996
American Society for Reproductive Medicine (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)81391-x · Cited by 3,018 · see citing works
Molecular cloning and expression of human hepatocyte growth factor
Nakamura, T., Nishizawa, T., Hagiya, M., Seki, T., Shimonishi, M., Sugimura, A., Tashiro, K., & Shimizu, S. (1989) · Nature · doi:10.1038/342440a0 · Cited by 2,158 · see citing works
Sonnenberg, E., Meyer, D., Weidner, K. M., & Birchmeier, C. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.123.1.223 · Cited by 699 · see citing works
Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor
Miyazawa, K., Tsubouchi, H., Naka, D., Takahashi, K., Okigaki, M., Arakaki, N., Nakayama, H., Hirono, S., Sakiyama, O., Takahashi, K., et al. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92316-4 · Cited by 653 · see citing works
Evidence for the identity of human scatter factor and human hepatocyte growth factor.
Weidner, K. M., Arakaki, N., Hartmann, G. R., Vandekerckhove, J. S., Weingart, S., Rieder, H., Fonatsch, C., Tsubouchi, H., HISHIDA, T., & Daikuhara, Y. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7001 · Cited by 653 · see citing works
Nakamura, T., Teramoto, H., & Ichihara, A. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.17.6489 · Cited by 592 · see citing works
Vascular endothelial growth factor (VEGF) in endometriosis
Donnez, J., Smoes, P., Gillerot, S., Casanas-Roux, F., & Nisolle, M. (1998) · Human Reproduction · doi:10.1093/humrep/13.6.1686 · Cited by 531 · see citing works
McLaren, J. F., Prentice, A., Jones, D. S., & Smith, S. K. (1996) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a019023 · Cited by 350 · see citing works
Nonpigmented endometriosis: Clinical, laparoscopic, and pathologic definition
Jansen, R. P. S., & Russell, P. (1986) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(86)90136-5 · Cited by 345 · see citing works
Tseng, J. F., Ryan, I., Milam, T. D., Murai, J. T., Schriock, E. D., LANDERS, D. V., & Taylor, R. N. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.3.8772585 · Cited by 291 · see citing works
Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis
Rana, N., Braun, D. P., House, R., Gebel, H., Rotman, C., & Dmowski, W. P. (1996) · Fertility and Sterility · doi:10.1016/s0015-0282(16)58262-4 · Cited by 264 · see citing works
Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis.
Harada, T., Yoshioka, H., Yoshida, S., Iwabe, T., Onohara, Y., Tanikawa, M., & Terakawa, N. (1997) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(97)70553-2 · Cited by 258 · see citing works
Taketani, Y., KUO, T.-M., & Mizuno, M. (1992) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(11)91672-x · Cited by 243 · see citing works
Endocrinology and paracrinology
Arici, A. M., Tazuke, S. I., Kliman, H. J., & Olive, D. L. (1996) · Molecular Human Reproduction · doi:10.1093/molehr/2.1.40 · Cited by 201 · see citing works
Punnonen, J., Teisala, K., Ranta, H., Bennett, B., & Punnonen, R. (1996) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(96)70600-2 · Cited by 176 · see citing works
Tajima, H., Matsumoto, K., & Nakamura, T. (1992) · Experimental Cell Research · doi:10.1016/0014-4827(92)90095-p · Cited by 169 · see citing works
Vascular endothelial growth factor and interleukin-6 in peritoneal fluid of women with endometriosis
Mahnke, J. L., Dawood, M. Y., & Huang, J.-C. (2000) · Fertility and Sterility · doi:10.1016/s0015-0282(99)00466-5 · Cited by 165 · see citing works
Structural and functional characterization of the mouse hepatocyte growth factor gene promoter.
Liu, Y., Michalopoulos, G. K., & Zarnegar, R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41756-x · Cited by 162 · see citing works
Differential macrophage infiltration in early and advanced endometriosis and adjacent peritoneum
Khan, K. N., Masuzaki, H., Fujishita, A., Kitajima, M., Sekine, I., & Ishimaru, T. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.07.037 · Cited by 161 · see citing works
Self-citationNisolle, M., Casanas-Roux, F., & Donnez, J. (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)00341-5 · Cited by 148 · see citing works
Osteen, K. G., Hill, G. A., Hargrove, J. T., & Gorstein, F. (1989) · Fertility and Sterility · doi:10.1016/s0015-0282(16)53160-4 · Cited by 127 · see citing works
Olive oil, other seasoning fats, and the risk of colorectal carcinoma
Braga, C., Vecchia, C. L., Franceschi, S., Negri, E., Parpinel, M. T., Decarli, A., Giacosa, A., & Trichopoulos, D. (1998) · Cancer · doi:10.1002/(sici)1097-0142(19980201)82:3 · Cited by 126 · see citing works
Tsudo, T., Harada, T., Iwabe, T., Tanikawa, M., Nagano, Y., Ito, M., Taniguchi, F., & Terakawa, N. (2000) · Fertility and Sterility · doi:10.1016/s0015-0282(99)00496-3 · Cited by 124 · see citing works
Khan, K. N., Masuzaki, H., Fujishita, A., Kitajima, M., Sekine, I., Matsuyama, T., & Ishimaru, T. (2005) · Human Reproduction · doi:10.1093/humrep/deh897 · Cited by 123 · see citing works
Self-citationSugawara, J., Fukaya, T., Murakami, T., Yoshida, H., & Yajima, A. (1997) · Biology of Reproduction · doi:10.1095/biolreprod57.4.936 · Cited by 110 · see citing works
Khan, K. N., Masuzaki, H., Fujishita, A., Kitajima, M., Sekine, I., & Ishimaru, T. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(02)04535-1 · Cited by 78 · see citing works
Self-citationRegulation of HGF and HGFR gene expression
Zarnegar, R. (1995) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0348-9070-0_3 · Cited by 73 · see citing works
Immunohistochemical Study of Angiogenic Factors in Endometrium and Endometriosis
Fujishita, A., Hasuo, A., Khan, K. N., Masuzaki, H., Nakashima, H., & Ishimaru, T. (1999) · Gynecologic and Obstetric Investigation · doi:10.1159/000052867 · Cited by 55 · see citing works
Self-citationHigher activity by opaque endometriotic lesions than nonopaque lesions
Khan, K. N., Masuzaki, H., Fujishita, A., Kitajima, M., Sekine, I., & Ishimaru, T. (2004) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/j.0001-6349.2004.00229.x · Cited by 54 · see citing works
Self-citationKhan, K. N., Masuzaki, H., Fujishita, A., Kitajima, M., Kohno, T., Sekine, I., Matsuyama, T., & Ishimaru, T. (2004) · Human Reproduction · doi:10.1093/humrep/deh525 · Cited by 49 · see citing works
Self-citationHepatocyte growth factor concentrations are elevated in peritoneal fluid of women with endometriosis
Osuga, Y., Tsutsumi, O., Okagaki, R., Takai, Y., Fujimoto, A., Suenaga, A., Maruyama, M., Momoeda, M., Yano, T., & Taketani, Y. (1999) · Human Reproduction · doi:10.1093/humrep/14.6.1611 · Cited by 47 · see citing works
Khan, K. N., Masuzaki, H., Fujishita, A., Hamasaki, T., Kitajima, M., Hasuo, A., Miyamura, Y., & Ishimaru, T. (2002) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1034/j.1600-0412.2002.810814.x · Cited by 45 · see citing works
Self-citationNegami, A. I., Sasaki, H., Kawakami, Y., KAMITANI, N., Kotsuji, F., Tominaga, T., & Nakamura, T. (2008) · Hormone Research · doi:10.1159/000184660 · Cited by 34 · see citing works
Nonpigmented endometriosis; Clinical, laparoscopic, and pathologic definition
Jansen, R., & Russel, P. (1987) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(87)90391-2 · Cited by 24 · see citing works
Determination of HGF concentration in serum and peritoneal fluid in women with endometriosis.
Zong, L., Li, Y., & Ha, X.-Q. (2003) · PubMed · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Peripheral biomarkers of endometriosis: a systematic review
May, K. E., Conduit-Hulbert, S. A., Villar, J., Kirtley, S., Kennedy, S. H., & Becker, C. M. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmq009 · Cited by 418 · see citing works
Blood biomarkers for the non-invasive diagnosis of endometriosis
Nisenblat, V., Bossuyt, P. M., Shaikh, R., Farquhar, C. M., Jordan, V., Scheffers, C. S., Mol, B. W., JOHNSON, N. P., & Hull, M. L. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012179 · Cited by 388 · see citing works
Update on biomarkers for the detection of endometriosis
Fassbender, A., Burney, R. O., F. O, D., D’Hooghe, T., & Giudice, L. (2015) · BioMed Research International · doi:10.1155/2015/130854 · Cited by 195 · see citing works
“Hepatocyte growth factor (HGF) was suggested to be elevated in women with endometriosis [72], although this was not confirmed in an additional study [23, 73].”
Laschke, M. W., & Menger, M. D. (2007) · Human Reproduction Update · doi:10.1093/humupd/dmm006 · Cited by 177 · see citing works
Angiogenesis and Endometriosis
Rocha, A. L. L., dos Reis, F. M., & Taylor, R. N. (2013) · Obstetrics and Gynecology International · doi:10.1155/2013/859619 · Cited by 162 · see citing works
Khan, K. N., Kitajima, M., Hiraki, K., Fujishita, A., Sekine, I., Ishimaru, T., & Masuzaki, H. (2008) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2008.00643.x · Cited by 125 · see citing works
Self-citationThe role of iron in the pathogenesis of endometriosis
Kobayashi, H., Yamada, Y., Kanayama, S., Furukawa, N., 野口, 武., Haruta, S., Yoshida, S., Sakata, M., Sado, T., & Oi, H. (2009) · Gynecological Endocrinology · doi:10.1080/09513590802366204 · Cited by 97 · see citing works
Fatores ambientais e endometriose
Bellelis, P., Podgaec, S., & Abrão, M. S. (2011) · Revista da Associação Médica Brasileira · doi:10.1590/s0104-42302011000400022 · Cited by 68 · see citing works
Environmental factors and endometriosis
Bellelis, P., Podgaec, S., & Brão, M. M. (2011) · Revista da Associação Médica Brasileira (English Edition) · doi:10.1016/s2255-4823(11)70093-5 · Cited by 64 · see citing works
Toll-like receptor 4-mediated growth of endometriosis by human heat-shock protein 70
Khan, K. N., Kitajima, M., Imamura, T., Hiraki, K., Fujishita, A., Sekine, I., Ishimaru, T., & Masuzaki, H. (2008) · Human Reproduction · doi:10.1093/humrep/den195 · Cited by 62 · see citing works
Self-citationEndometriosis-associated ovarian cancer: What have we learned so far?
Herreros‐Villanueva, M., Chen, C.-C., Tsai, E., & Er, T. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.02.016 · Cited by 57 · see citing works
Nair, A. S., Nair, H. B. B., Lucidi, R. S., Kirchner, A. J., Schenken, R. S., TEKMAL, R. R., & Witz, C. A. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.09.047 · Cited by 53 · see citing works
Yerlikaya‐Schatten, G., Balendran, S., Proestling, K., Reischer, T., Birner, P., Wenzl, R. J., Kuessel, L., Streubel, B., & Husslein, H. (2016) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2016.07.500 · Cited by 51 · see citing works
Schneider, C., Kässens, N., Greve, B., Hassan, H., Schüring, A. N., Starzinski‐Powitz, A., Kiesel, L., Seidler, D. G., & Götte, M. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.10.051 · Cited by 46 · see citing works
Environmental factors and endometriosis
Bellelis, P., Podgaec, S., & Brão, M. M. (2011) · Revista da Associação Médica Brasileira · doi:10.1016/s0104-4230(11)70093-8 · Cited by 42 · see citing works
Current Knowledge on Endometriosis Etiology: A Systematic Review of Literature
Михалева, Л. М., Radzinsky, V. E., Orazov, M. R., Николаевна, Х. Т., Sorokina, A. V., Александрович, М. С., Владимировна, В. С., Shustova, V. B., & Sinelnikov, M. Y. (2021) · International Journal of Women s Health · doi:10.2147/ijwh.s306135 · Cited by 37 · see citing works
Elevated serum interleukin‐32 levels in patients with endometriosis: A cross‐sectional study
Choi, Y. S., Kim, S., Oh, Y. S., Cho, S., & Kim, S. H. (2019) · American Journal of Reproductive Immunology · doi:10.1111/aji.13149 · Cited by 23 · see citing works
Khan, K. N., Kitajima, M., Hiraki, K., Fujishita, A., Nakashima, M., & Masuzaki, H. (2015) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2015.01.012 · Cited by 20 · see citing works
Self-citationKhoshdelRad, N., Salehi, Z., Mashayekhi, F., Abbasi, O., & Mirzajani, E. (2014) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-013-3082-7 · Cited by 17 · see citing works
Vascular Endothelial Growth Factor Serum Levels in Women with Advanced Endometriosis
Măluţan, A. M. (2016) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2016.7 · Cited by 15 · see citing works
The Double Engines and Single Checkpoint Theory of Endometriosis
Hsu, C.-F., Khine, A. A., Huang, H.-S., & Chu, T.-Y. (2022) · Biomedicines · doi:10.3390/biomedicines10061403 · Cited by 12 · see citing works
Clinical markers of endometriosis: Have we been too quick to judge?
Toor, K. K., Wessels, J. M., Agarwal, S. K., Leyland, N. A., & Foster, W. G. (2014) · Medical Hypotheses · doi:10.1016/j.mehy.2014.02.007 · Cited by 10 · see citing works
Heidari, S., Kolahdouz‐Mohammadi, R., Khodaverdi, S., Mohammadi, T., & Delbandi, A. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17592 · Cited by 8 · see citing works
Biomarkers of endometriosis - current trends
Adamyan, L. V., & Aznaurova, Y. B. (2018) · Russian Journal of Human Reproduction · doi:10.17116/repro201824157-62 · Cited by 7 · see citing works
Signorile, P. G., Baldi, A., Viceconte, R., Vincenzi, B., & Montella, M. (2023) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukaryotgeneexpr.2023047178 · Cited by 4 · see citing works
Fasolato, S., Bianco, P. D., Malacrida, S., Mattiolo, A., Gringeri, E., Angeli, P., Pontisso, P., & Calabrò, M. L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713432 · Cited by 3 · see citing works
Endometriosis and the Hallmarks of Cancer
Ellis, K. B., & Wood, R. (2025) · Reproductive Sciences · doi:10.1007/s43032-025-02024-0 · Cited by 3 · see citing works
Peripheral Blood Biomarkers for Endometriosis
Fassbender, A., Dorien, O., Becker, C. M., & D’Hooghe, T. M. (2017) · Springer eBooks · doi:10.1007/978-3-319-59856-7_7 · Cited by 2 · see citing works
The Implication of Angiogenesis in Endometriosis
Ilie, R., & Ilie, I. R. P. (2014) · Cited by 1 · see citing works
Decreased occurrence of endometriosis in women with Chlamydia trachomatis infection
Khan, K. N., Fujishita, A., Kitajima, M., Ishimaru, T., Ogawa, K., Koshiba, A., Mori, T., & Kitawaki, J. (2021) · American Journal of Reproductive Immunology · doi:10.1111/aji.13498 · Cited by 1 · see citing works
Self-citationPadrões de resposta imune em pacientes com endometriose
Podgaec, S. (2006) · doi:10.11606/t.5.2006.tde-31102006-105026 · Cited by 1 · see citing works
Role of Nerve Fibres in Endometriosis
Tokushige, N. (2014) · Springer eBooks · doi:10.1007/978-4-431-54421-0_13
(2007) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0b013e3282ca75fc
Phytochemicals Modulating Receptor Tyrosine Kinase Signaling Networks in Endometriosis
Hsu, C., & Weng, C. (2026) · Pharmaceuticals · doi:10.3390/ph19091413
- Authors
- KHAN, K. N., MASUZAKI, H., FUJISHITA, A., KITAJIMA, M., HIRAKI, K., MIURA, S., SEKINE, I., & ISHIMARU, T.
- Affiliations
- Nagasaki Municipal Hospital (JP)
- Atomic Bomb Disease Institute, Nagasaki University (JP)
- Corresponding author
- KHAN, KHALEQUE NEWAZ
- Venue
- Acta Obstetricia et Gynecologica Scandinavica
- Publisher
- Wiley
- Published
- 2006-04
- Volume
- 85
- Issue
- 4
- Pages
- 458-466
- ISSN
- 0001-6349 (ISSN-L)
- 1600-0412
- OpenAlex
- W2003573799
- Cited by
- 36
- References
- 35
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Acta Obstetricia Et Gynecologica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Nagasaki University's Academic Output SITE (Nagasaki University) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Surgery › Diagnosis and treatment of tuberculosis
- Keywords
- endometriosis, hepatocyte growth factor, peritoneal fluid, serum biomarkers, endometrioma, macrophages, stromal cells, lipopolysaccharide stimulation, peritoneal lesions, endometriosis recurrence
- MeSH terms
- Adolescent, Adult, Ascitic Fluid, Endometriosis, Enzyme-Linked Immunosorbent Assay, Female, Humans, Peritoneum, Predictive Value of Tests, Sensitivity and Specificity, Hepatocyte Growth Factor, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
