Expression of the Hippo Pathway Core Components in Endometrial Cancer and Its Association with Clinicopathologic Features
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Collection
2.2. TMA and Immunohistochemical Stain
2.3. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Immunohistochemical Staining in Endometrial Cancer
3.3. Association between YAP Expression and Core Proteins
3.4. Association between Clinicopathological Features and Expression of YAP, p-YAP, and LATS1/2
3.5. Logistic Regression Analysis of YAP and P-YAP Expression
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Gu, B.; Shang, X.; Yan, M.; Li, X.; Wang, W.; Wang, Q.; Zhang, C. Variations in incidence and mortality rates of endometrial cancer at the global, regional, and national levels, 1990–2019. Gynecol. Oncol. 2021, 161, 573–580. [Google Scholar] [CrossRef]
- Urick, M.E.; Bell, D.W. Clinical actionability of molecular targets in endometrial cancer. Nat. Rev. Cancer 2019, 19, 510–521. [Google Scholar] [CrossRef] [PubMed]
- Kong, A.; Johnson, N.; Kitchener, H.C.; Lawrie, T.A. Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst. Rev. 2012, 18, CD003916. [Google Scholar]
- Kong, A.; Johnson, N.; Kitchener, H.C.; Lawrie, T.A. Adjuvant radiotherapy for stage I endometrial cancer: An updated Cochrane systematic review and meta-analysis. J. Natl. Cancer Inst. 2012, 104, 1625–1634. [Google Scholar] [CrossRef] [Green Version]
- Colombo, N.; Creutzberg, C.; Querleu, D.; Barahona, M.; Sessa, C. Appendix 5: Endometrial cancer: eUpdate published online 8 June 2017 (www.esmo.org/Guidelines/Gynaecological-Cancers). Ann. Oncol. 2017, 28, iv153–iv156. [Google Scholar] [CrossRef] [PubMed]
- Concin, N.; Matias-Guiu, X.; Creutzberg, C.L.; Vergote, I.; Cibula, D.; Mirza, M.R.; Marnitz, S.; Ledermann, J.; Bosse, T.; Chargari, C.; et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Virchows Arch. 2021, 478, 153–190. [Google Scholar] [CrossRef]
- An, H.J.; Song, D.H.; Kim, Y.-M.; Jo, H.C.; Baek, J.C.; Park, J.E. Significance of HER2 and VEGFR2 in Early-stage Endometrial Cancer. In Vivo 2022, 36, 723–730. [Google Scholar] [CrossRef] [PubMed]
- Besso, M.J.; Montivero, L.; Lacunza, E.; Argibay, M.C.; Abba, M.; Furlong, L.I.; Colas, E.; Gil-Moreno, A.; Reventos, J.; Bello, R.; et al. Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools. Oncol. Rep. 2020, 44, 873–886. [Google Scholar] [CrossRef] [PubMed]
- Fatima, I.; Barman, S.; Rai, R.; Thiel, K.W.; Chandra, V. Targeting Wnt Signaling in Endometrial Cancer. Cancers 2021, 13, 2351. [Google Scholar] [CrossRef]
- Stelloo, E.; Nout, R.A.; Osse, E.M.; Jurgenliemk-Schulz, I.J.; Jobsen, J.J.; Lutgens, L.C.; van der Steen-Banasik, E.M.; Nijman, H.W.; Putter, H.; Bosse, T.; et al. Improved risk assessment by integrating molecular and clinicopathological factors in early-stage endometrial cancer-combined analysis of the PORTEC cohorts. Clin. Cancer Res. 2016, 22, 4215–4224. [Google Scholar] [CrossRef] [PubMed]
- Harvey, K.F.; Pfleger, C.M.; Hariharan, I.K. The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis. Cell 2003, 114, 457–467. [Google Scholar] [CrossRef] [Green Version]
- Udan, R.S.; Kango-Singh, M.; Nolo, R.; Tao, C.; Halder, G. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat. Cell Biol. 2003, 5, 914–920. [Google Scholar] [CrossRef] [PubMed]
- Wu, S.; Huang, J.; Dong, J.; Pan, D. hippo Encodes a Ste-20 Family Protein Kinase that Restricts Cell Proliferation and Promotes Apoptosis in Conjunction with salvador and warts. Cell 2003, 114, 445–456. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boopathy, G.T.K.; Hong, W. Role of hippo pathway-YAP/TAZ signaling in angiogenesis. Front. Cell Dev. Biol. 2019, 7, 49. [Google Scholar] [CrossRef] [PubMed]
- Pulkkinen, H.H.; Kiema, M.; Lappalainen, J.P.; Toropainen, A.; Beter, M.; Tirronen, A.; Holappa, L.; Niskanen, H.; Kaikkonen, M.U.; Ylä-Herttuala, S.; et al. BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF. Angiogenesis 2021, 24, 129–144. [Google Scholar] [CrossRef]
- Harvey, K.F.; Zhang, X.; Thomas, D.M. The Hippo pathway and human cancer. Nat. Rev. Cancer 2013, 13, 246–257. [Google Scholar] [CrossRef]
- Liu, Q.; Liu, X.; Song, G. The Hippo Pathway: A Master Regulatory Network Important in Cancer. Cells 2021, 10, 1416. [Google Scholar] [CrossRef]
- Moon, S.H.; Hwang, S.M.; Kim, B.S.; Lee, S.Y.; Kim, H.K.; Lee, G.W.; Hong, K.H.; Song, H.; Choi, Y.S. Hippo Signaling in the Endometrium. Int. J. Mol. Sci. 2022, 23, 3852. [Google Scholar] [CrossRef] [PubMed]
- Rausch, V.; Hansen, C.G. The hippo pathway, YAP/TAZ, and the plasma membrane. Trends Cell Biol. 2020, 30, 32–48. [Google Scholar] [CrossRef] [PubMed]
- Dong, J.; Feldmann, G.; Huang, J.; Wu, S.; Zhang, N.; Comerford, S.A.; Gayyed, M.F.; Anders, R.A.; Maitra, A.; Pan, D. Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals. Cell 2007, 130, 1120–1133. [Google Scholar] [CrossRef] [PubMed]
- Badouel, C.; McNeill, H. SnapShot. The hippo signaling pathway. Cell 2011, 145, 484.e1. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Romero-Pérez, L.; Garcia-Sanz, P.; Mota, A.; Leskelä, S.; Hergueta-Redondo, M.; Diaz-Martin, J.; López-García, M.A.; Castilla, M.A.; Martínez-Ramírez, A.; Soslow, R.; et al. A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer. Mod. Pathol. 2015, 28, 1492–1503. [Google Scholar] [CrossRef] [Green Version]
- Yu, F.-X.; Zhao, B.; Guan, K.L. Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. Cell 2015, 163, 811–828. [Google Scholar] [CrossRef] [Green Version]
- Mohajan, S.; Jaiswal, P.K.; Vatanmakarian, M.; Yousefi, H.; Sankaralingam, S.; Alahari, S.K.; Koul, S.; Koul, H.K. Hippo pathway: Regulation, deregulation and potential therapeutic targets in cancer. Cancer Lett. 2021, 507, 112–123. [Google Scholar] [CrossRef]
- Varelas, X. The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 2014, 141, 1614–1626. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Pasolli, H.A.; Fuchs, E. Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proc. Natl. Acad. Sci. USA 2011, 108, 2270–2275. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, B.; Ye, X.; Yu, J.; Li, L.; Li, W.; Li, S.; Yu, J.; Lin, J.D.; Wang, C.-Y.; Chinnaiyan, A.M.; et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008, 22, 1962–1971. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, C.; Mao, D.; Hua, G.; Lv, X.; Chen, X.; Angeletti, P.C.; Dong, J.; Remmenga, S.W.; Rodabaugh, K.J.; Zhou, J.; et al. The Hippo/ YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression. EMBO Mol. Med. 2015, 7, 1426–1449. [Google Scholar] [CrossRef]
- Yang, N.; Morrison, C.D.; Liu, P.; Miecznikowski, J.; Bshara, W.; Han, S.; Zhu, Q.; Omilian, A.R.; Li, X.; Zhang, J. TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin. Cell Cycle 2012, 11, 2922–2930. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cordenonsi, M.; Zanconato, F.; Azzolin LForcato, M.; ARosato, A.; Frasson, C.; Inui, M.; Montagner, M.; Parenti, A.R.; Poletti, A.; Daidone, M.G.; et al. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 2011, 147, 759–772. [Google Scholar] [CrossRef]
- Zhang, C.; Liang, K.; Zhou, G.; Zhang, Q.; Li, J. Expression of hippo pathway in colorectal cancer. Saudi J. Gastroenterol. 2014, 20, 188–194. [Google Scholar] [CrossRef]
- Zhou, G.X.; Li, X.Y.; Zhang, Q.; Zhao, K.; Zhang, C.P.; Xue, C.H.; Yang, K.; Tian, Z.B. Effects of the Hippo signaling pathway in human gastric cancer, Asian Pac. J. Cancer Prev. Asian Pac. J. Cancer Prev. 2013, 14, 5199–5205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Su, L.-L.; Ma, W.-X.; Yuan, J.-F.; Shao, Y.; Xiao, W.; Jiang, S.-J. Expression of Yes-associated protein in non-small cell lung cancer and its relationship with clinical pathological factors. Chin. Med. J. 2012, 125, 4003–4008. [Google Scholar]
- Zhou, Y.; Tao, F.; Cheng, Y.; Xu, F.; Yao, F.; Feng, D.; Miao, L.; Xiao, W.; Ling, B. Up-regulation of ITCH is associated with down-regulation of LATS1 during tumorigenesis and progression of cervical squamous cell carcinoma. Clin. Investig. Med. 2014, 37, E384–E394. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, B.; Sun, D.; Wang, Z.; Weng, H.; Wu, D.; Zhang, X.; Zhou, Y.; Hu, W. Expression of LATS family proteins in ovarian tumors and its significance. Hum. Pathol. 2015, 46, 858–867. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Vega, F.; Mina, M.; Armenia, J.; Chatila, W.K.; Luna, A.; La, K.C.; Dimitriadoy, S.; Liu, D.L.; Kantheti, H.S.; Saghafinia, S.; et al. Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell 2018, 173, 321–337.e10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, D.; He, J.; Dong, J.; Meyer, T.F.; Xu, T. The HIPPO pathway in gynecological malignancies. Am. J. Cancer Res. 2020, 10, 610–629. [Google Scholar] [PubMed]
- Lewin, S.N.; Herzog, T.J.; Barrena Medel, N.I.; Deutsch, I.; Burke, W.M.; Sun, X.; Wright, J. Comparative performance of the 2009 international Federation of gynecology and obstetrics’ staging system for uterine corpus cancer. Obstet. Gynecol. 2010, 116, 1141–1149. [Google Scholar] [CrossRef] [PubMed]
- Creasman, W.T.; Odicino, F.; Maisonneuve, P.; Quinn, M.A.; Beller, U.; Benedet, J.L.; Heintz, A.P.M.; Ngan, H.Y.S.; Pecorelli, S. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int. J. Gynaecol Obstet. 2006, 95 (Suppl. 1), S105–S143. [Google Scholar] [CrossRef] [PubMed]
- Ma, S.; Wu, Z.; Yang, F.; Zhang, J.; Johnson, R.L.; Rosenfeld, M.G.; Guan, K.-L. Hippo signalling maintains ER expression and ER+ breast cancer growth. Nature 2021, 591, E1–E10. [Google Scholar] [CrossRef] [PubMed]
- Britschgi, A.; Duss, S.; Kim, S.; Couto, J.P.; Brinkhaus, H.; Koren, S.; De Silva, D.; Mertz, K.D.; Kaup, D.; Varga, Z.; et al. The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ER alpha. Nature 2017, 541, 541–545. [Google Scholar] [CrossRef] [PubMed]
- Wang, R.; Zhu, G. A narrative review for the Hippo-YAP pathway in cancer survival and immunity: The Yin-Yang dynamics. Transl. Cancer Res. 2022, 11, 262–275. [Google Scholar] [CrossRef] [PubMed]
- Britschgi, A.; Couto, J.P.; Bentires-Alj, M. Reply to: Hippo signalling maintains ER expression and ER+ breast cancer growth. Nature 2021, 591, E11–E12. [Google Scholar] [CrossRef] [PubMed]
- Liu, T.; Liu, Y.; Gao, H.; Meng, F.; Yang, S.; Lou, G. Clinical significance of yes-associated protein overexpression in cervical carcinoma: The differential effects based on histotypes. Int. J. Gynecol. Cancer Off. J. Int. Gynecol. Cancer Soc. 2013, 23, 735–742. [Google Scholar] [CrossRef] [PubMed]
- Tsujiura, M.; Mazack, V.; Sudol, M.; Kaspar, H.G.; Nash, J.; Carey, D.J.; Gogoi, R. Yes-Associated Protein (YAP) Modulates Oncogenic Features and Radiation Sensitivity in Endometrial Cancer. PLoS ONE 2014, 9, e100974. [Google Scholar] [CrossRef] [PubMed]
Variable | Value | |
---|---|---|
Age, years (mean [range]) | 51 [35–78] | |
<60 years, n (%) | 49 (81.7) | |
≥60 years, n (%) | 11 (18.3) | |
Menopause, n (%) | No | 26 (43.3) |
Yes | 34 (56.7) | |
FIGO stage, n (%) | 1A | 42 (70.0) |
1B | 11 (18.3) | |
2 | 2 (3.3) | |
3A | 2 (3.3) | |
3B | 1 (1.7) | |
3C | 2 (3.3) | |
Histologic grade, n (%) | 1 | 40 (66.7) |
2 | 15 (25) | |
3 | 5 (8.3) | |
* Tumour size, n (%) | <2 cm | 16 (28.6) |
≥2 cm and <4 cm | 18 (32.1) | |
≥4 cm | 22 (39.3) | |
LVSI, n (%) | Negative | 54 (90.0) |
Positive | 6 (10.0) | |
Myometrial invasion, n (%) | <1/2 | 35 (58.3) |
≥1/2 | 25 (41.7) | |
† YAP expression, n (%) | Negative | 11 (18.3) |
Positive | 45 (75.0) | |
Non-informative | 4 (3.7) | |
† p-YAP expression, n (%) | Negative | 11 (18.3) |
Positive | 44 (73.3) | |
Non-informative | 5 (8.3) | |
† MST1/2, n (%) | Negative | 35 (58.3) |
Positive | 16 (26.7) | |
Non-informative | 9 (15.0) | |
† KIBRA, n (%) | negative | 45 (75.0%) |
positive | 10 (16.7%) | |
Non-informative | 5 (8.3%) | |
† Merlin, n (%) | Negative | 40 (66.7) |
Positive | 9 (15.0) | |
Non-informative | 11 (18.3) | |
† LATS1/2, n (%) | Negative | 49 (81.7) |
Positive | 9 (15.0) | |
Non-informative | 2 (3.3) |
YAP | p-YAP | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Negative | Positive | p Value | Univariable OR (95% CI) | p Value | Negative | Positive | p Value | Univariable OR (95% CI) | p Value | ||
* MST1/2 n (%) | Negative | 8 (100.0) | 27 (62.8) | 0.045 | - | 8 (80.0) | 27 (65.9) | 0.474 | 2.07 (0.44–14.99) | 0.394 | |
Positive | 0 (0.0) | 16 (37.2) | 2 (20.0) | 14 (34.1) | |||||||
KIBRA n (%) | Negative | 8 (100.0) | 35 (77.8) | 0.327 | - | 10 (90.9) | 33 (78.6) | 0.667 | 2.73 (1.69–7.06) | 0.368 | |
Positive | 0 (0.0) | 10 (22.2) | 1 (9.1) | 9 (21.4) | |||||||
* Merlin n (%) | Negative | 7 (87.5) | 33 (80.5) | >0.990 | 1.70 (24–34.07) | 0.642 | 9 (90.0) | 31 (79.5) | 0.663 | 2.32 (0.35–46.03) | 0.454 |
Positive | 1 (12.5) | 8 (19.5) | 1 (10.0) | 8 (20.5) | |||||||
LATS1/2 | Negative | 8 (80.0) | 39 (86.7) | 0.627 | - | 8 (72.7) | 39 (90.7) | 0.140 | - | ||
Positive | 2 (20.0) | 6 (13.3) | 3 (27.3) | 4 (9.3) | |||||||
p-YAP n (%) | Negative | 5 (55.6) | 6 (13.3) | 0.03 | 8.13 (1.72–42.38) | 0.009 | - | ||||
Positive | 4 (44.4) | 39 (86.7) |
YAP Expression | p-YAP Expression | LATS1/2 Expression | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Clinicopathological Feature | Negative (n = 11) | Positive (n = 45) | p Value | Negative (n = 11) | Positive (n = 44) | p Value | Negative (n = 49) | Positive (n = 9) | p Value | |
Age | <60 years | 5 (45.5%) | 40 (88.9%) | 0.004 | 8 (72.7%) | 37 (84.1%) | 0.400 | 39 (79.6%) | 8 (88.9%) | >0.990 |
≥60 years | 6 (54.5%) | 5 (11.1%) | 3 (27.3%) | 7 (15.9%) | 10 (20.4%) | 1 (11.1%) | ||||
Menopause | No | 3 (27.3%) | 20 (44.4%) | 0.496 | 4 (36.4%) | 19 (43.2%) | 0.745 | 20 (40.8%) | 4 (44.4%) | >0.990 |
Yes | 8 (72.7%) | 25 (55.6%) | 7 (63.6%) | 25 (56.8%) | 29 (59.2%) | 5 (55.6%) | ||||
FIGO stage | 1 | 10 (90.9%) | 39 (86.7%) | >0.990 | 9 (81.8%) | 39 (88.6%) | 0.617 | 43 (87.8%) | 8 (88.9%) | >0.990 |
2.3 | 1 (9.1%) | 6 (13.3%) | 2 (18.2%) | 5 (11.4%) | 6 (12.2%) | 1 (11.1%) | ||||
Histologic grade | 1 | 7 (63.6%) | 41 (91.1%) | 0.732 | 7 (63.6%) | 31 (70.5%) | 0.722 | 31 (63.3%) | 7 (77.8%) | 0.476 |
2.3 | 4 (36.4%) | 4 (8.9%) | 4 (36.4%) | 13 (29.5%) | 18 (36.7%) | 2 (22.2%) | ||||
LVSI | Negative | 9 (81.8%) | 42 (93.3%) | 0.251 | 9 (81.8%) | 41 (93.2%) | 0.259 | 45 (91.8%) | 7 (77.8%) | 0.231 |
Positive | 2 (18.2%) | 3 (6.7%) | 2 (18.2%) | 3 (6.8%) | 4 (8.2%) | 2 (22.2%) | ||||
MI | <1/2 | 3 (27.3%) | 29 (64.4%) | 0.041 | 4 (36.4%) | 27 (61.4%) | 0.180 | 27 (55.1%) | 6 (66.7%) | 0.718 |
≥1/2 | 8 (72.7%) | 16 (35.6%) | 7 (63.6%) | 17 (38.6%) | 22 (44.9%) | 3 (33.3%) | ||||
* Tumour size (n = 52) | <4 cm | 7 (63.6%) | 23 (56.1%) | 0.741 | 2 (18.2%) | 22 (55.0%) | 0.030 | 28 (62.2%) | 4 (44.4%) | 0.461 |
≥4 cm | 4 (36.4%) | 18 (43.9%) | 9 (73.8%) | 18 (45.0%) | 17 (37.8%) | 5 (55.6%) |
Clinicopathologic Feature | YAP Expression (n = 56) | p-YAP Expression (n = 55) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Univariable OR (95% CI) | p Value | (1) Multivariable OR (95% CI) | p Value | (2) Stepwise † (95% CI) | p Value | Univariable OR (95% CI) | p Value | (3) Multivariable OR (95% CI) | p Value | (4) Stepwise † (95% CI) | p Value | |
Age ≥ 60 | 0.18 (0.04–0.81) | 0.024 | 0.14 (0.02–0.80) | 0.033 | 0.13 (0.02–0.63) | 0.013 | 0.50 (0.11–2.72) | 0.388 | 0.36 (0.04–2.71) | 0.313 | - | |
Menopause | 0.47 (0.09–1.86) | 0.306 | 0.86 (0.11–6.46) | 0.880 | - | 0.75 (0.18–2.87) | 0.682 | 0.72 (0.13–3.96) | 0.704 | - | ||
Histologic grade 1 | 1.26 (0.29–4.93) | 0.738 | 0.82 (0.15–4.02) | 0.811 | - | 1.36 (0.31–5.36) | 0.662 | 0.76 (0.13–3.68) | 0.742 | - | ||
LVSI | 0.32 (0.05–2.70) | 0.249 | 0.16 (0.01–1.69) | 0.113 | 0.19 (0.02–1.85) | 0.126 | 0.33 (0.05–2.77) | 0.259 | 0.36 (0.04–3.74) | 0.363 | - | |
MI | 0.35 (0.08–1.32) | 0.129 | 0.33 (0.06–1.48) | 0.156 | 0.35 (0.07–1.49) | 0.164 | 0.58 (0.15–2.19) | 0.418 | 0.80 (0.18–3.58) | 0.769 | - | |
* Tumour size ≥ 4 cm | 1.15 (0.30–4.50) | 0.838 | 1.46 (0.30–7.89) | 0.640 | - | 0.15 (0.02–0.68) | 0.026 | 0.14 (0.02–0.70) | 0.030 | 0.15 (0.02–0.68) | 0.026 |
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Yang, J.; Song, D.H.; Kim, C.H.; Kim, M.H.; Jo, H.C.; Kim, H.; Park, J.E.; Baek, J.C. Expression of the Hippo Pathway Core Components in Endometrial Cancer and Its Association with Clinicopathologic Features. Diagnostics 2022, 12, 2973. https://doi.org/10.3390/diagnostics12122973
Yang J, Song DH, Kim CH, Kim MH, Jo HC, Kim H, Park JE, Baek JC. Expression of the Hippo Pathway Core Components in Endometrial Cancer and Its Association with Clinicopathologic Features. Diagnostics. 2022; 12(12):2973. https://doi.org/10.3390/diagnostics12122973
Chicago/Turabian StyleYang, Juseok, Dae Hyun Song, Cho Hee Kim, Min Hye Kim, Hyen Chul Jo, Hyoeun Kim, Ji Eun Park, and Jong Chul Baek. 2022. "Expression of the Hippo Pathway Core Components in Endometrial Cancer and Its Association with Clinicopathologic Features" Diagnostics 12, no. 12: 2973. https://doi.org/10.3390/diagnostics12122973