Table 1.
The expression and the role of Galectin-1, -3, -7 and -9 in tumor progression, treatment, and prognosis of gynecological cancers.
| Cancer types | Expression and role | Treatment and effect | Prognostic significance |
|---|---|---|---|
| Cervical cancer |
Galectin 1: High galectin-1 was detected in cytoplasm, nuclei and stroma of cervical cancer cells, while galectin-1 expression was negative or absent in normal cervical tissue samples 35. Increased galectin-1 expression was associated with lymph node metastasis and tumor invasion 31. Galectin-1 expression in stromal cells was gradually increased according to the pathological grade i.e. from normal cervical tissues to LGSIL, HGSIL and ISCC 34. |
Mediated the radio-resistance in cervical cancer through H-Ras dependent pathways 36. High galectin-1 inhibited radiation mediated cell death and involved in DNA damage repair 36. Galectin-1 antibody has potential role as reliable adoptive immunotherapy for cervical cancer patients 38. Galectin-1 expression may act as a potential predictive biomarker to cisplatin-based neoadjuvant chemotherapy response in cervical cancer patients 39. |
Galectin-1 expression was not associated with the 5-year progression free survival 32. Galectin-1 expression in squamous cervical cancer cells was associated with both 10-year local recurrence and 10-year cancer specific survival, but could not predict distant metastasis 34. Strong expression of galectin-1 by tumor cells was significantly correlated with poor disease-free and disease-specific survival in patients with squamous cervical cancer 31. |
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Galectin 3: Galectin-3 was expressed in cervical tumor, usually in cytoplasm, nucleus and plasma membrane 49. High expression in ISCC and HGSIL compared with normal and LGSIL, suggesting that galectin-3 expression declined according to progression. Associated with decreased tumor invasion and the presence of human papilloma virus 31. Expression increased by VEGF-c via NF-kB pathway and activated disease with increased invasiveness 51. Positive galetin-3 protein expression was significantly higher in CIN, including CIN grade I, II and III and in cervical cancer compared with healthy normal cervix 50. |
N/A | High expression of galectin-3 is associated with poor prognosis 50, 52 Overexpression of galectin-3 was significantly associated with decreased survival rate compared to those with low expressions 50. The 5-year survival rate of CC patients with an AA genotype of rs11125 in galectin-3 was markedly higher than those presented with an AT+TT genotype (71.05% vs 42%), whereas, 5-year survival rate of patients carrying a CC+CA genotype of rs11125 was significantly lower than that of AA genotype carrier (88.89% vs 54.63%) 52. |
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Galectin 7: High expression documented in cytoplasm and nuclei of cancer cells. Healthy cervical tissue compared with CIN II (40.4%), CIN III (13.9%) and SCC tissue showed a significant decrease in the high staining proportion of galectin-7. Galectin-7 knock-down significantly promoted invasion through increasing MMP-9 expression and activating P13K/Akt signaling pathway 72, 73. Hela cells expressing galectin-7 were more invasive than HeLa cells. Galectin-7 expression induced the transformation of HeLa cells in cervical adenocarcinoma to more invasive cells via MMP-9 in association with p38 signaling pathway 74. |
Galectin-7 increased the sensitivity to concurrent chemo-radiotherapy in cervical cancer and can act as a protective therapeutic role 72, 73. | Galectin-7 high expression was correlated with better clinical outcomes following radiation treatment for cervical cancer. Negative galectin-7 expression was related with decrease rate of DMFS, DSS and OS 75, 76. SCC patients with negative galectin-7 staining had profoundly decreased 5-year OS rate compared with positive staining 73. |
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Galectin 9: Galectin-9 was detected in normal epithelium and endocervical glands but those in CIN and SCC were significantly faint. Galectin-9 in WSCC was significantly high compared to those in HSIL. Galectin-9 in SCC was inversely correlated with the grade of differentiation (WSCC >> MSCC >> PSCC) 78. Galectin-9 was expressed by tumor cells in 11% of samples. Tumor cell expression of galectin-9 showed a trend toward improved survival 31. |
N/A | N/A | |
| Ovarian cancer |
Galectin 1: Galectin-1 was mostly noted in peritumoral stroma and cytoplasm of ovarian cancer cells but not displayed in normal ovarian tissues 40-43. Elevated galectin-3 was significantly associated with advanced stage EOC (stage III-IV > stage I-II) 41. Galectin-1 may interact with H-Ras and activate ERK pathway promoting malignancy of EOC by cell invasion and proliferation 41. TLR4 mediated PI3K activation stimulates the invasive and migratory capacity of ovarian cancer cells through galectin-1 production 45. |
Galectin-1 transfected in Hey (low galectin-1 expression) cells displayed decreased sensitivity to Cisplatin compared to GFP transfectants 41. Galectin-1 can be a potential therapeutic option contributing in cisplatn resistance in EOC cells 41. OTX008 or the compound aiming for galectin-1 may contribute to better ovarian cancer treatment 80. |
Galectin-1 overexpression was primarily found with increased Recurrent rate in 3-years 42 and shorter PFS 40, 41 than that in the weak expressing EOC patients. Galectin-1 expression in the cytoplasm was profoundly associated with decreased OS compared to negative galectin-1 expression patients 43. |
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Galectin 3: Predominatly located in nuclei and cytoplasm of ovarian cancer cells but absent in normal or healthy tissues 54-58. Associated with Ki-67L1 and FIGO stage III and IV compared to stage I and II of CCCs 60. Overexpression led to increase cells invasion, migration, proliferation and modulated stemness factor, while down-regulation of galectin-3 with specific siRNA reversed those biological phenomenon [60 61, 62]. |
High galectin-3 up-regulated the release of cytokines (IL-6 and IL-8) and inhibited the cisplatin and paclitaxel-mediated cell death 62, 64. Increases sensitivity to paclitaxel treatment and galectin-3C blocked angiogenesis 54, 56, 63. Low galectin-3 augmented the response of ovarian cancer cells to carboplatin 61. |
High galectin-3 was correlated with poor PFS compared with reduced galectin-3 expression 54, 57. Galectin-3 was significantly associated with disease recurrence, especially with the presence of local recurrence, carcinomatosis, lymphoadenpathies and distant metastasis. High level of galectin-3 staining other than in nuclei showed significantly decreased OS compared to patients with nuclear staining 43 , 58. |
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Galectin 7: Highly expressed in the cytoplasm and nuclei. Stronger expression was revealed in serous type and weakest in endometrioid type. It was associated with larger tumor volume and increased proliferation rate compared with low galectin-7 expression 43. Galectin-7 was markedly higher with advanced grade, borderline and metastatic tumors of EOC in contrast to benign tumors 77. |
N/A | Galectin-7 expression indicated poor prognosis in ovarian cancer with high mortality and decreased overall survival outcomes. High galectin-7 expression was successively independent prognostic factors for poor OS in EOC patients 77. Low galectin-7 markedly correlated with favorable OS and increased galectin-7 expression is conferred as an independent prognostic factor for OS in ovarian cancer 43. |
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Galectin 9: Galectin-9 staining was mostly found in the cytoplasm of ovarian cancer cells. Cases with high galectin-9 expression presented a significant association with low tumor stage, early FIGO stage, and younger age 79. |
N/A | Kaplan-Meier analysis showed that moderate galectin-9 expression had a decreased PFS and OS compared to galectin-9 negative cases. Intriguingly, patients with high galectin-9 expression displayed the best PFS and OS 79. | |
| Endometrial cancer |
Galectin 1: Galectin-1 expression was notably elevated in cytoplasm of cancer cells than adjacent normal endometrium 47. |
N/A | N/A |
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Galectin 3: Galectin-3 expression in endometrial cancer was reduced compared with normal or benign menopausal endometrium 47, 65. Expression in endometrial cancer was reduced compared with normal or benign menopausal endometrium. Mostly in the cytoplasm and/or nucleus and membrane. Elevated galectin-3 immunostaining was documented more frequently with increased age and grade I, whereas loss or decreased expression was noted in grade II and III or poorly differentiated cancers 66, 67. High expression of galectin-3 promotes cell adhesion, cell growth cycle and cell proliferation in cancer cell 71. Galectin-3 expression increased from normal endometrium (NE), simple hyperplasia (SH), complex hyperplasia (CH) and Atypical hyperplasia (AH) to the adenocarcinoma 68. |
N/A | Galectin-3 is related with poor prognosis and shorter survival rate in endometrioid cancer patients 69. | |
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Galectin 7: N/A |
N/A | N/A | |
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Galectin 9: N/A |
N/A | N/A |
Abbreviations: LGSIL, low grade squamous intraepithelial lesion; HGSIL, high grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia; SCC, squamous cell carcinoma; ISCC, invasive squamous cell carcinoma; WSCC, well-differentiated SCC; MSCC, moderately differentiated SCC; PSCC, poorly differentiated SCC; EOC, epithelial ovarian cancer; FIGO, international federation of gynecology and obstetrics stage; DMFS, distant metastasis free survival; DSS; disease-specific survival; OS, overall survival; PFS, progression-free survival.