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Table 1 LGALS3BP expression and prognostic significance in human cancers

From: Role of galectin 3 binding protein in cancer progression: a potential novel therapeutic target

Cancer incidence and mortality rate (%)

Samples and analysis

Prognostic significance

References

Breast cancer (11.7%–6.9%)

I. IHC analysis in 2 independent set of primary tumors derived from patients with resected unilateral cancer without nodal involvement: Training set (N = 170)—Validation set (N = 120)

II. IHC analysis in 249 invasive breast cancer patients

I. LGALS3BP high expression predicts worse DFS (p < 0.007), DRFS (p < 0.008) and OS (p < 0.01)

II. LGALS3BP high expression predicts earlier development of distant metastasis and shorter patient survival in the ER-negative group (p = 0.0353) and not in ER-positive group

[13]

[14]

I. Sandwich-type ELISA of serum samples from 185 patients with breast cancer, 56 patients with benign breast disease and 165 healthy donors

II. Sandwich-type ELISA of serum samples from 425 breast cancer patients with no evidence of disease after surgery (NED), 310 patients with metastasis and 285 healthy female blood donors

I. Abnormal LGALS3BP levels are present in a greater percentage of breast cancer patients compared to healthy controls and benign breast disease patients. High LGALS3BP correlates with tumor staging (p < 0.01), and with tumor burden, as its levels decreases after surgical removal

II. LGALS3BP expression level is higher in breast cancer patients compared to healthy donors, and it positively correlates with shorter OS in node-positive NED patients (p = 0.004). Regarding patients with developed metastatic disease, there is a positive correlation with metastatic liver involvement (p = 0.009), a shorter disease-free interval (p = 0.005) and a younger age (p = 0.01)

[11]

[12]

Lung cancer (11.4%–18%)

I. IHC analysis of surgically resected stage I NSCLC (Non-Small Cells Lung Cancer) tumors from 72 patients

II. IHC analysis of primary lung carcinoma tissues resected from 28 at the time of surgical removal

I. LGALS3BP high expression is strongly associated with chance of developing distant metastasis at various time intervals from complete resection. LGALS3BP positively correlates with shorter 5-year DFS and OS (p = 0.0001 and p = 0.0003, respectively)

II. Protein expression of LGALS3BP is strongly associated with clinical staging of lung carcinoma, although difference is not statistically significant

[26]

[27]

I. ELISA analysis of serum samples from 320 lung cancer patients and 80 healthy donors

I. Serum concentrations of LGALS3BP in lung cancer patients are significantly higher than those in healthy controls (p < 0.05). Positive correlation with tumor histology (p = 0.000), lymph node metastases (p = 0.022), and distant metastases (p = 0.001). LGALS3BP concentrations above cut off value (6 mg/ml) correlate with poor OS (p = 0.000)

[28]

Melanoma (1.7%–0.6%)

I. Sandwich-type ELISA of serum samples from 128 patients with melanoma, of which 117 treated with immunotherapy and 11 with placebo

II. Sandwich-type ELISA on sera collected from 117 randomly selected malignant melanoma patients, who were enrolled into melanoma therapy trials

I. LGALS3BP high expression predicts risk of recurrence or progression (p = 0.0079), and represents a potential early marker for response to immunotherapy

II. Elevated LGALS3BP expression is associated with tumor stage and age and predicts increased risk of melanoma progression during follow-up (p = 0.03)

[32]

[34]

Ovarian cancer (1.6%, 2.1%)

I. IHC analysis of ~ 210 primary early-stage (stage I/ II) ovarian cancer tissues of mixed histologies organized in two TMAs

I. LGALS3BP expression is heavily associated with stage tumor (p < 0.0001), higher risk of tumour recurrence (p = 000001) and with optimal debulking status (p = 0.018) as well as patient age (p = 0.005). I Positive correlation with worse OS is found but not with statistical significance (p = 0.075)

[39]

I. Sandwich-type ELISA on sera collected from 73 ovarian cancer patients and 70 patients with benign gynaecological conditions

II. Sandwich-type ELISA on serum samples from 152 patients, who underwent primary surgery for epithelial ovarian cancer

I. Compared to patients with benign ovarian tumors, LGALS3BP serum level is significantly higher in ovarian cancer patients. Statistically significant correlation of high LGALS3BP expression with grade of tumor differentiation and chemotherapy response

II. Serum antigen LGALS3BP levels are positively correlated with residual disease and tumor grade (p < 0.05). LGALS3BP concentrations above cut off value (6.3 U/ml) correlate with an unfavourable clinical course (p < 0.03)

[37]

[38]

Hepatocellular carcinoma (4.7%–8.3%)

I. Sandwich-type ELISA on serum samples from 11 chronic active hepatitis (CAH), 48 liver cirrhosis and 36 HCC patients

II. Sandwich-type ELISA on serum samples from 172 patients, of which 103 patients with liver cirrhosis and 69 patients with HCC

III. Sandwich-type ELISA on serum samples from 40 cirrhotic HCC at first diagnosis

I. According to a cut-off point of 14 mg/mL for LGALS3BP, increasing positivity is observed from CAH to liver cirrhosis and HCC

II. Abnormally high serum levels of LGALS3BP are present in a greater percentage of HCC patients compared to cirrhosis patients, often associated with anti-HCV antibodies presence

III. LGALS3BP levels are significantly higher in HCC patients with more than one lesion. Patients with serum LGALS3BP below the cut off value (14 ng/ml) show improved OS (p = 0.02)

[44]

[43]

[45]

Pancreatic cancer (2.6%, 4.7%)

I. IHC analysis of pancreatic carcinoma tissues from 28 patients undergoing a partial duodenopancreatectomy (Whipple resection)

I. LGALS3BP is strongly expressed, but no significant prognostic correlation is observed

[47]

Prostatic cancer (7.3%, 3.8%)

I. IHC analysis of TMA containing four morphologically representative areas of tissue from 300 patients, of which 286 had evidence of prostate cancer

I. LGALS3BP is over-expressed in prostate cancer tissues and mostly lost in PIN, but no significant clinical correlation is observed

[51]

Oral squamous cell carcinoma (2.0%, 1.8%)

I. IHC analysis of tissues derived from 146 OSCC patients

II. IHC analysis of tissues derived from 92 OSCC patients

I. LGALS3BP expression significantly correlates with the differentiation status of OSCC (p = 0.006), with the highest positive rate seen in cases of well-differentiated OSCC

II. Elevated expression levels of LGALS3BP are significantly associated with poorer clinicopathological features, including higher T stages (p = 0.043), more recurrence (p = 0.002) and shorter OS (p < 0.0001)

[53]

[56]

I. Sandwich-type ELISA on serum samples collected from 91 OSCC patients and 106 healthy controls

II. ELISA on saliva samples collected from 117 various stages OSCC subjects (including 30 cases of PMODs and 42 control subjects matched according to age, sex and socioeconomic status

I. Serum levels of LGALS3BP are significantly higher in OSCC patients versus healthy controls (p < 0.0001), but this is not statistically associated with various clinicopathological characteristics, although patients with well-differentiated carcinoma or advanced clinical stage tend to have higher LGALS3BP levels

II. LGALS3BP is a highly significant indicator in OSCC stage I-II patients and high risk PMODs with p = 0.0008 and p = 0.0001, respectively; but is not discriminatory for late stage OSCC

[53]

[57]

Neuroblastoma

I. Sandwich-type ELISA on serum samples collected at diagnosis from 47 patients with different stages of neuroblastoma disease and 38 controls samples collected from age-matched healthy children, admitted for accidental traumatic injuries

I. LGALS3BP concentration is significantly higher in sera from neuroblastoma patients than in sera from healthy children (p = 0.0005). LGALS3BP serum levels above the cut off level (91.47 ng/ml) significantly correlate with a higher incidence of relapse (p = 0.032)

[62]

Glioblastoma multiforme (1.6%, 2.5%)

I. IHC analysis of 508 primary GBM tumor cases and 10 adjacent normal tissue cases

I. LGALS3BP is significantly upregulated in GBM tissues compared with adjacent normal tissues and its high expression significantly correlates with shorter OS (p = 0.013)

[65]

Gastric cancer (5.6%, 7.7%)

I. IHC analysis of 22 samples of gastric cancer tissues

I. LGALS3BP expression is higher in cancerous tissues compared with the normal mucosal tissues. No information regarding the prognostic value are present

[66]

I. ELISA on sera obtained from 36 gastric cancer patients and 9 healthy donors

I. LGALS3BP concentrations are significantly higher in gastric cancer patients compared to healthy blood donors (p = 0.0012). Moreover, higher serum levels positively correlate with distant metastasis occurrence and with tumor stage (p = 0.05 and p = 0.04, respectively)

[66]

Lymphoma (NHL: 2.8%, 2.6%; HL: (0.4%, 0.2%)

I. Sandwich-type ELISA on serum samples collected from 137 patients with lymphoma diagnosed and treated [116 with non-Hodgkin lymphoma (NHL) and 21 with Hodgkin lymphoma (HL)], and 50 control serum samples from blood donors

I. Serum LGALS3BP levels in patients with NHL are significantly higher compared to healthy blood donors (p < 0.001), but not compared to patients with HL (p = 0.2). Higher serum LGALS3BP concentrations significantly correlate with bone marrow involvement in patients with NHL (p = 0.04); and it represents a good marker of treatment response prediction (p = 0 .011)

[67]

Colon carcinoma (6.0%, 5.8%)

I. IHC analysis of 196 paraffin-embedded, archival primary colorectal cancer tissues

I. High LGALS3BP expression correlates with a higher DFS rate (p = 0.011) and with a longer OS (p < 0.002)

[80]

I. ELISA on serum samples obtained from 20 AD (adenoma) and 20 ADK (adenocarcinoma) patients, as well as from 15 healthy donors

II. ELISA on serum samples from 198 CRC patients who received colon cancer resection, of which 174 without clinically detectable metastasis and 24 with liver metastasis

I.Significantly higher levels of LGALS3BP protein are present in AD and ADK patients compared to healthy donors (AD: p = 0.009; ADK: p = 0.0001). No information regarding the prognostic value are present

II. High LGALS3BP expression correlates with tumor stage and size (p = 0.014 and p < 0.001, respectively)

[68]

[73]

Mesothelioma (0.2%, 0.3%)

I. ELISA on serum samples and PEs (pleural effusions) from 57 cases, of which 28 diagnosed as MM, 14 as LC (lung cancer) and 15 as BPD (benign pleural disease)

I. LGALS3BP level in PEs is significantly higher in MM patients compared to LC (p = 0.011) or BPD (p = 0.021) patients, while no significant differences is detected (p > 0.05) in mean serum LGALS3BP levels between the three groups. LGALS3BP serum levels above the cut off level (7.3 mg/ml) correlates with increased survival probability (p < 0.05)

[81]

Ewing’s sarcoma

I. IHC analysis of TMA with formalin-fixed paraffin embedded tumor specimens from 274 Ewing’s sarcoma patients

I. LGALS3BP expression is associated with better EFS (Event-Free Survival) and OS (p = 0.04 and p = 0.03, respectively)

[82]

I. ELISA on serum samples from 75 Ewing’s sarcoma patients

I. No association between LGALS3BP levels and prognosis is observed

[82]