Cell division cycle 37 change after bortezomib-based induction therapy helps to predict clinical response and prognosis in multiple myeloma patients

Figures & data

Table 1. Clinical characteristics.

Items	Multiple myeloma patients (N = 82)
Demographic characteristics
Age (years), mean ± standard deviation	67.0 ± 9.2
Gender, No. (%)
Female	31 (37.8)
Male	51 (62.2)
Immunoglobulin subtype, No. (%)
Immunoglobulin G	40 (48.8)
Immunoglobulin A	21 (25.6)
Others	21 (25.6)
Bone lesion, No. (%)
No	25 (30.5)
Yes	57 (69.5)
Renal impairment, No. (%)
No	49 (59.8)
Yes	33 (40.2)
Biochemical indexes
Hemoglobin (g/L), median (interquartile range)	87.5 (66.8–102.5)
Calcium (mg/dL), median (interquartile range)	11.9 (10.7–13.0)
Serum creatinine (mg/dL), median (interquartile range)	1.8 (1.2–2.4)
Albumin (g/L), median (interquartile range)	32.0 (26.3–39.1)
Beta-2-microglobulin (mg/L), median (interquartile range)	5.5 (3.4–8.9)
Lactate dehydrogenase (U/L), median (interquartile range)	217.2 (187.3–282.4)
Cytogenetics
t (4; 14), No. (%)	13 (15.9)
t (14; 16), No. (%)	4 (4.9)
Del (17p), No. (%)	4 (4.9)
Prognostic stratification
International Staging System stage, No. (%)
Stage I	7 (8.5)
Stage II	34 (41.5)
Stage III	41 (50.0)
Revised International Staging System stage, No. (%)
Stage I	4 (4.9)
Stage II	55 (67.1)
Stage III	23 (28.0)
Treatment information
Regimens, No. (%)
bortezomib, lenalidomide, and dexamethasone	21 (25.6)
bortezomib, thalidomide, and dexamethasone	61 (74.4)
Autologous hematopoietic stem cell transplantation, No. (%)
No	59 (72.0)
Yes	23 (28.0)

Figure 1. Comparison of CDC37 among multiple myeloma patients, disease controls, and healthy controls.

Table 2. Correlation of CDC37 expression with clinical characteristics in multiple myeloma patients.

Items	CDC37 expression at baseline Median (interquartile range)	r value	P value
Age (years)	-	0.003	0.981
Gender		-	0.109
Female	3.310 (2.280–4.490)
Male	2.660 (1.690–3.970)
Immunoglobulin subtype		-	0.724
Immunoglobulin G	3.020 (1.990–4.113)
Immunoglobulin A	3.300 (1.735–4.525)
Others	2.710 (1.665–3.905)
Bone lesion		-	0.339
No	2.550 (1.600–4.180)
Yes	3.290 (1.965–3.905)
Renal impairment		-	0.066
No	2.550 (1.660–3.835)
Yes	3.350 (2.175–4.325)
Hemoglobin (g/L)	-	−0.110	0.325
Calcium (mg/dL)	-	0.128	0.253
Serum creatinine (mg/dL)	-	0.263	0.017
Albumin (g/L)	-	−0.038	0.735
Beta-2-microglobulin (mg/L)	-	0.244	0.027
Lactate dehydrogenase (U/L)	-	0.150	0.179
t (4; 14)		-	0.126
No	2.710 (1.760–3.940)
Yes	3.350 (2.455–5.145)
t (14; 16)		-	0.175
No	2.860 (1.860–3.903)
Yes	5.290 (1.965–7.348)
Del (17p)		-	0.484
No	3.020 (1.860–3.925)
Yes	3.445 (1.858–8.438)
International Staging System stage		-	0.100
Stage I	2.260 (1.870–3.660)
Stage II	3.170 (1.633–3.950)
Stage III	3.290 (2.150–4.425)
Revised International Staging System stage		-	0.041
Stage I	2.170 (1.923–2.523)
Stage II	2.900 (1.690–3.870)
Stage III	3.670 (2.020–5.280)

CDC37, cell division cycle 37.

Continuous variables were shown using r value and P value; while categorical variables were shown using CDC37 expression at baseline and P value.

Figure 2. CDC37 at baseline reflected poor treatment response and survival in multiple myeloma patients. Correlation of CDC37 at baseline with complete response (A), objective response (B), progression-free survival (C), and overall survival (D) in multiple myeloma patients.

Figure 3. Comparison of CDC37 at baseline and after induction treatment in multiple myeloma patients.

Figure 4. CDC37 after induction treatment reflected poor treatment response and survival in multiple myeloma patients. Correlation of CDC37 after induction treatment with complete response (A), objective response (B), progression-free survival (C), and overall survival (D) in multiple myeloma patients.

Table 3. Cox’s proportional hazards regression analysis for progression-free survival.

Items	P value	Hazard ratio	95% confidence interval
			Lower	Upper
Univariate Cox’s proportional hazards regression analysis
CDC37 expression at baseline (high vs. low)	0.037	2.038	1.046	3.970
CDC37 expression after induction treatment (high vs. low)	0.008	2.567	1.285	5.128
Age (>60 years vs. ≤ 60 years)	0.629	1.214	0.552	2.671
Gender (male vs. female)	0.125	0.596	0.308	1.155
Immunoglobulin subtype
Immunoglobulin G	Reference
Immunoglobulin A	0.690	0.855	0.397	1.842
Others	0.500	0.752	0.329	1.721
Bone lesion (yes vs. no)	0.515	1.273	0.615	2.632
Renal impairment (yes vs. no)	0.834	1.073	0.555	2.073
Hemoglobin (abnormal vs. normal)	0.075	2.216	0.922	5.326
Calcium (abnormal vs. normal)	0.289	0.697	0.358	1.359
Serum creatinine (abnormal vs. normal)	0.834	1.073	0.555	2.073
Albumin (abnormal vs. normal)	0.020	2.542	1.160	5.571
Beta-2-microglobulin (abnormal vs. normal)	0.040	2.012	1.033	3.920
Lactate dehydrogenase (abnormal vs. normal)	0.112	1.702	0.884	3.280
Cytogenetics (t (4; 14), t (14; 16), or Del (17p) vs. no)	0.359	1.392	0.686	2.821
Higher International Staging System stage	0.015	2.051	1.150	3.659
Higher revised International Staging System stage	0.003	2.474	1.366	4.481
Treatment (bortezomib, thalidomide, and dexamethasone vs. bortezomib, lenalidomide, and dexamethasone)	0.847	1.073	0.525	2.190
Autologous hematopoietic stem cell transplantation (yes vs. no)	0.026	0.389	0.170	0.893
Forward-multivariate Cox’s proportional hazards regression analysis
CDC37 expression after induction treatment (high vs. low)	0.023	2.257	1.121	4.544
Higher revised International Staging System stage	0.009	2.212	1.218	4.016

CDC37, cell division cycle 37.

Hemoglobin was divided with the cut-off value of 100 g/L; Calcium was divided with the cut-off value of 12 mg/dL; serum creatinine was divided with the cut-off value of 2 mg/dL; albumin was divided with the cut-off value of 35 g/L; Beta-2-microglobulin was divided with the cut-off value of 5.5 mg/L; lactate dehydrogenase was divided with the cut-off value of 220 U/L.

Table 4. Cox’s proportional hazards regression analysis for overall survival.

Items	P value	Hazard ratio	95% confidence interval
			Lower	Upper
Univariate Cox’s proportional hazards regression analysis
CDC37 expression at baseline (high vs. low)	0.132	2.013	0.809	5.005
CDC37 expression after induction treatment (high vs. low)	0.011	4.165	1.396	12.429
Age (>60 years vs. ≤ 60 years)	0.764	0.865	0.335	2.236
Gender (male vs. female)	0.228	0.582	0.242	1.403
Immunoglobulin subtype
Immunoglobulin G	Reference
Immunoglobulin A	0.165	0.453	0.148	1.386
Others	0.153	0.403	0.116	1.403
Bone lesion (yes vs. no)	0.764	1.168	0.424	3.223
Renal impairment (yes vs. no)	0.356	1.499	0.634	3.545
Hemoglobin (abnormal vs. normal)	0.347	1.688	0.567	5.026
Calcium (abnormal vs. normal)	0.516	0.747	0.309	1.803
Serum creatinine (abnormal vs. normal)	0.356	1.499	0.634	3.545
Albumin (abnormal vs. normal)	0.090	2.564	0.862	7.628
Beta-2-microglobulin (abnormal vs. normal)	0.054	2.541	0.984	6.564
Lactate dehydrogenase (abnormal vs. normal)	0.174	1.882	0.756	4.683
Cytogenetics (t (4; 14), t (14; 16), or Del (17p) vs. no)	0.210	1.762	0.727	4.273
Higher International Staging System stage	0.044	2.422	1.025	5.723
Higher revised International Staging System stage	0.030	2.424	1.089	5.393
Treatment (bortezomib, thalidomide, and dexamethasone vs. bortezomib, lenalidomide, and dexamethasone)	0.988	1.007	0.403	2.516
Autologous hematopoietic stem cell transplantation (yes vs. no)	0.023	0.097	0.013	0.727
Forward-multivariate Cox’s proportional hazards regression analysis
CDC37 expression after induction treatment (high vs. low)	0.022	3.580	1.199	10.692
Autologous hematopoietic stem cell transplantation (yes vs. no)	0.034	0.113	0.015	0.848

CDC37, cell division cycle 37.

Hemoglobin was divided with the cut-off value of 100 g/L; Calcium was divided with the cut-off value of 12 mg/dL; serum creatinine was divided with the cut-off value of 2 mg/dL; albumin was divided with the cut-off value of 35 g/L; Beta-2-microglobulin was divided with the cut-off value of 5.5 mg/L; lactate dehydrogenase was divided with the cut-off value of 220 U/L.