Spliced X-Box binding protein 1 predicts satisfying responsiveness and survival benefit toward bortezomib-based therapy in multiple myeloma patients

Figures & data

Table 1 . Clinical characteristics of MM patients.

Items	MM patients (N = 97)
Age (years), smean ± SD	60.8 ± 8.7
Female	38 (39.2)
Immunoglobulin subtype, No. (%)
IgG	46 (47.4)
IgA	21 (21.6)
Others	30 (30.9)
Bone lesion, No. (%)	64 (66.0)
Renal impairment, No. (%)	40 (41.2)
Hb (g/L), mean ± SD	99.2 ± 22.1
Calcium (mg/dL), median (IQR)	9.8 (8.7–11.3)
Scr (mg/dL), median (IQR)	1.8 (1.3–2.1)
ALB (g/L), median (IQR)	34.0 (28.5–37.5)
β2-MG (mg/L), median (IQR)	5.7 (3.0–9.5)
LDH (U/L), median (IQR)	210.7 (182.3–252.6)
Cytogenetics, No. (%)
t (4; 14)	10 (10.3)
t (14; 16)	2 (2.1)
Del (17p)	6 (6.2)
R-ISS, No. (%)
I	9 (9.3)
II	42 (43.3)
III	46 (47.4)

MM, multiple myeloma; SD, standard deviation; IgG, immunoglobulin G; IgA, immunoglobulin A; Hb, hemoglobin; IQR, interquartile range; Scr, serum creatinine; ALB, albumin; β₂-MG, Beta-2-microglobulin; LDH, lactate dehydrogenase; R-ISS, revised International Staging System.

Figure 1 . The expression of sXBP1 in MM patients, DCs, and HCs. sXBP1, spliced X-Box binding protein 1; MM, multiple myeloma; DCs, disease controls, HCs, health controls.

Figure 2 . ROC curves of sXBP1 in discriminating different subjects. ROC curves of sXBP1 in discriminating MM patients from DCs (A); ROC curve of sXBP1 in discriminating MM patients from HCs (B). ROC, receiver operating characteristic; sXBP1, spliced X-Box binding protein 1; MM, multiple myeloma; DCs, disease controls, HCs, health controls.

Figure 3 . Elevated sXBP1 was linked with better treatment response to bortezomib in MM patients. sXBP1 in MM patients with CR and non-CR (A); ROC curve of sXBP1 in discriminating CR patients from non-CR patients (B); sXBP1 in MM patients with ORR and non-ORR (C); ROC curve of sXBP1 in discriminating ORR patients from non-ORR patients (D). sXBP1, spliced X-Box binding protein 1; MM, multiple myeloma; CR, complete response; ROC, receiver operating characteristic; ORR, objective response rate.

Figure 4 . sXBP1 high was linked with longer PFS and OS. Association of sXBP1 (high vs. low) with PFS (A) and OS (B) in MM patients. MM patients were divided into sXBP1 high and sXBP1 low according to the median value of sXBP1 mRNA expression. sXBP1, spliced X-Box binding protein 1; PFS, progression-free survival; OS, overall survival; MM, multiple myeloma.

Table 2 . Cox’s proportional hazards regression analysis for PFS.

Items	P value	HR	95% CI
			Lower	Upper
Univariate Cox’s analysis for PFS
sXBP1 expression (high vs. low)	0.013	0.465	0.254	0.853
Age (>60 years vs. ≤60 years)	0.503	1.222	0.680	2.199
Gender (male vs. female)	0.135	0.637	0.353	1.150
Immunoglobulin subtype
Others	Reference
IgG	0.347	1.419	0.684	2.945
IgA	0.142	1.827	0.817	4.087
Bone lesion (yes vs. no)	0.088	1.781	0.917	3.459
Renal impairment (yes vs. no)	0.011	2.152	1.193	3.881
Hb (>100 g/L vs. ≤100 g/L)	0.009	0.426	0.225	0.805
Calcium (>12 mg/dL vs. ≤12 mg/dL)	0.851	1.080	0.482	2.422
Scr (>2 mg/dL vs. ≤2 mg/dL)	0.438	1.271	0.694	2.327
ALB (>35 g/L vs. ≤35 g/L)	0.013	0.380	0.177	0.817
β2-MG (>5.5 mg/L vs. ≤5.5 mg/L)	0.003	2.628	1.374	5.025
LDH (>220 U/L vs. ≤220 U/L)	0.030	1.942	1.068	3.531
t (4; 14) (yes vs. no)	0.002	3.258	1.546	6.865
t (14; 16) (yes vs. no)	0.002	11.223	2.383	52.862
Del (17p) (yes vs. no)	0.658	0.767	0.236	2.486
Higher Durie-Salmon stage	0.207	1.740	0.736	4.117
Higher ISS	0.001	2.568	1.448	4.555
Higher R-ISS	0.001	2.685	1.524	4.731
Multivariate backward-stepwise Cox’s analysis for PFS
sXBP1 expression (high vs. low)	0.025	0.481	0.254	0.911
Renal impairment (yes vs. no)	0.020	2.787	1.177	6.598
ALB (>35 g/L vs. ≤35 g/L)	0.053	0.454	0.204	1.011
β2-MG (>5.5 mg/L vs. ≤5.5 mg/L)	0.012	2.812	1.255	6.302
t (4; 14) (yes vs. no)	0.004	3.095	1.433	6.684
t (14; 16) (yes vs. no)	0.001	17.998	3.298	98.230

MM patients were divided into sXBP1 high and sXBP1 low according to the median value of sXBP1 mRNA expression. PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; sXBP1, spliced- X-Box binding Protein 1; IgG, immunoglobulin G; IgA, immunoglobulin A; Hb, hemoglobin; Scr, serum creatinine; ALB, albumin; β2-MG, Beta-2-microglobulin; LDH, lactate dehydrogenase; ISS, International Staging System; R-ISS, revised International Staging System.

Table 3 . Cox’s proportional hazards regression analysis for OS.

Items	P value	HR	95% CI
			Lower	Upper
Univariate Cox’s analysis for OS
sXBP1 expression (high vs. low)	0.053	0.411	0.167	1.010
Age (>60 years vs. ≤60 years)	0.719	1.167	0.503	2.705
Gender (male vs. female)	0.050	0.430	0.185	1.000
Immunoglobulin subtype
Others	Reference
IgG	0.616	0.783	0.302	2.032
IgA	0.639	0.765	0.249	2.346
Bone lesion (yes vs. no)	0.116	2.386	0.806	7.066
Renal impairment (yes vs. no)	0.067	2.215	0.946	5.184
Hb (>100 g/L vs. ≤100 g/L)	0.473	0.732	0.312	1.717
Calcium (>12 mg/dL vs. ≤12 mg/dL)	0.235	1.832	0.674	4.978
Scr (>2 mg/dL vs. ≤2 mg/dL)	0.884	1.067	0.446	2.553
ALB (>35 g/L vs. ≤35 g/L)	0.323	0.604	0.222	1.641
β2-MG (>5.5 mg/L vs. ≤5.5 mg/L)	0.014	3.896	1.317	11.524
LDH (>220 U/L vs. ≤220 U/L)	0.214	1.738	0.727	4.156
t (4; 14) (yes vs. no)	0.039	2.690	1.051	6.885
t (14; 16) (yes vs. no)	0.163	4.282	0.555	33.022
Del (17p) (yes vs. no)	0.364	0.044	0.000	37.808
Higher Durie-Salmon stage	0.232	2.429	0.567	10.409
Higher ISS	0.013	3.547	1.301	9.665
Higher R-ISS	0.045	2.360	1.021	5.456
Multivariate backward-stepwise Cox’s analysis for OS
sXBP1 expression (high vs. low)	0.058	0.418	0.169	1.032
β2-MG (>5.5 mg/L vs. ≤5.5 mg/L)	0.002	6.312	1.993	19.986

MM patients were divided into sXBP1 high and sXBP1 low according to the median value of sXBP1 mRNA expression. OS, overall survival; HR, hazard ratio; CI, confidence interval; sXBP1, spliced- X-Box binding Protein 1; IgG, immunoglobulin G; IgA, immunoglobulin A; Hb, hemoglobin; Scr, serum creatinine; ALB, albumin; β2-MG, Beta-2-microglobulin; LDH, lactate dehydrogenase; ISS, International Staging System; R-ISS, revised International Staging System.