Prognostic Value and Clinical Significance of LIPH in Breast Cancer

Figures & data

Table 1 Clinicopathologic Characteristics According to Expression Level of LIPH in TCGA Databases

	Total (n=1090)	Expression		P-value*
		LIPH High (n=545)	LIPH Low (n=545)
Age (years)
≥55	517 (47.4%)	221 (40.6%)	296 (54.3%)	<0.001
<55	573 (52.6%)	324 (59.4%)	249 (45.7%)
T stage
T1	279 (25.6%)	148 (27.2%)	131 (24.0%)	0.557
T2	631 (57.9%)	306 (56.1%)	325 (59.6%)
T3	137 (12.6%)	67 (12.3%)	70 (12.8%)
T4	40 (3.7%)	22 (4.0%)	18 (3.3%)
Missing	3 (0.3%)	2 (0.4%)	1 (0.2%)
N stage
N0	514 (47.2%)	253 (46.4%)	261 (47.9%)	0.188
N1	360 (33.0%)	188 (34.5%)	172 (31.6%)
N2	120 (11.0%)	49 (9.0%)	71 (13.0%)
N3	76 (7.0%)	39 (7.2%)	37 (6.8%)
Missing	20 (1.8%)	16 (2.9%)	4 (0.7%)
M stage
M0	907 (83.2%)	458 (84.0%)	449 (82.4%)	0.75
M1	22 (2.0%)	10 (1.8%)	12 (2.2%)
Unknown	161 (14.8%)	77 (14.1%)	84 (15.4%)
AJCC stage
I	181 (16.6%)	99 (18.2%)	82 (15.0%)	0.485
II	621 (57.0%)	307 (56.3%)	314 (57.6%)
III	250 (22.9%)	118 (21.7%)	132 (24.2%)
IV	20 (1.8%)	10 (1.8%)	10 (1.8%)
Missing	18 (1.7%)	11 (2.0%)	7 (1.3%)
ER status
Negative	236 (21.7%)	102 (18.7%)	134 (24.6%)	0.0274
Positive	803 (73.7%)	421 (77.2%)	382 (70.1%)
Unknown	51 (4.7%)	22 (4.0%)	29 (5.3%)
PR status
Negative	343 (31.5%)	157 (28.8%)	186 (34.1%)	0.101
Positive	694 (63.7%)	364 (66.8%)	330 (60.6%)
Unknown	53 (4.9%)	24 (4.4%)	29 (5.3%)
HER2 status
Negative	895 (82.1%)	437 (80.2%)	458 (84.0%)	0.012
Positive	168 (15.4%)	99 (18.2%)	69 (12.7%)
Unknown	27 (2.5%)	9 (1.7%)	18 (3.3%)

Notes: Values are presented as number of patients (%); *χ² test was used.

Abbreviations: TCGA, The Cancer Genome Atlas; METABRIC, Molecular Taxonomy of Breast Cancer International Consortium; HER2, human epidermal growth factor receptor 2.

Table 2 Clinicopathologic Characteristics According to Expression Level of LIPH in METABRIC Databases

	Total (n=1904)	Expression		P-value*
		LIPH High (n=952)	LIPH Low (n=952)
Age (years)
≥55	952 (50.0%)	455 (47.8%)	497 (52.2%)	0.0602
<55	952 (50.0%)	497 (52.2%)	455 (47.8%)
Tumor size
≥2cm	592 (31.1%)	288 (30.3%)	304 (31.9%)	0.368
<2cm	1292 (67.9%)	659 (69.2%)	633 (66.5%)
Missing	20 (1.1%)	5 (0.5%)	15 (1.6%)
AJCC stage
0	4 (0.2%)	2 (0.2%)	2 (0.2%)	0.811
I	475 (24.9%)	229 (24.1%)	246 (25.8%)
II	800 (42.0%)	410 (43.1%)	390 (41.0%)
III	115 (6.0%)	61 (6.4%)	54 (5.7%)
IV	9 (0.5%)	4 (0.4%)	5 (0.5%)
Missing	501 (26.3%)	246 (25.8%)	255 (26.8%)
Tumor Grade
I	165 (8.7%)	99 (10.4%)	66 (6.9%)	0.0266
II	740 (38.9%)	366 (38.4%)	374 (39.3%)
III	927 (48.7%)	452 (47.5%)	475 (49.9%)
Missing	72 (3.8%)	35 (3.7%)	37 (3.9%)
ER status
Negative	445 (23.4%)	211 (22.2%)	234 (24.6%)	0.234
Positive	1459 (76.6%)	741 (77.8%)	718 (75.4%)
PR status
Negative	895 (47.0%)	444 (46.6%)	451 (47.4%)	0.783
Positive	1009 (53.0%)	508 (53.4%)	501 (52.6%)
HER2 status
Negative	1668 (87.6%)	839 (88.1%)	829 (87.1%)	0.531
Positive	236 (12.4%)	113 (11.9%)	123 (12.9%)

Notes: Values are presented as number of patients (%); *χ² test was used.

Abbreviations: METABRIC, Molecular Taxonomy of Breast Cancer International Consortium; HER2, human epidermal growth factor receptor 2.

Figure 1 LIPH expression pattern in breast cancer in TCGA database (A–H). (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001).

Abbreviation: ns, no significance.

Figure 2 Survival curves according to the expression level of LIPH using TCGA (A, C–H) and METABRIC (B) databases. PAM50: A 50-gene signature that classifies breast cancer into five molecular intrinsic subtypes: Luminal A, Luminal B, HER2-enriched, Basal-like, and Normal-like. Luminal A subtype (ER or PR positive, or both, HER2 negative); luminal B subtype (ER or PR positive, or both, HER2 negative); HER2 subtype (HER2 positive, ER or PR negative or positive); Basal subtype (HER2 negative and ER and PR negative).

Abbreviations: TCGA, The Cancer Genome Atlas; METABRIC, Molecular Taxonomy of Breast Cancer International Consortium; TNBC, triple-negative breast cancer.

Figure 3 Survival curves according to the expression level of LIPH in each subtype of breast cancer using METABRIC database (A–F).

Abbreviations: TCGA, The Cancer Genome Atlas; METABRIC, Molecular Taxonomy of Breast Cancer International Consortium; TNBC, triple-negative breast cancer; HER2, human epidermal growth factor receptor 2.

Table 3 Univariable Analyses Regarding Proportion Alive Using TCGA Databases

Characteristics	TCGA
	Univariable Analysis		Multivariable Analysis
	HR (95% CI)	P	HR (95% CI)	P
LIPH	1.17 (1.04–1.32)	0.01	1.22 (1.08–1.38)	0.001
Age	1.03 (1.02–1.05)	0	1.04 (1.02–1.05)	0
Stage	2.21 (1.76–2.76)	0	2.39 (1.92–2.98)	0
ER Positive	0.72 (0.5–1.04)	0.078	0.67 (0.39–1.16)	0.154
ER Unknown	1.98 (0.98–3.98)	0.056	7.37 (1.33–40.89)	0.022
PR Positive	0.74 (0.53–1.04)	0.084	0.68 (0.41–1.14)	0.145
PR Unknown	1.53 (0.75–3.12)	0.237	0.15 (0.02–0.89)	0.037
HER2 Positive	1.12 (0.71–1.77)	0.626	0.78 (0.48–1.27)	0.31
HER2 Unknown	2.61 (1.44–4.75)	0.002	1.89 (0.9–3.93)	0.091

Abbreviations: TCGA, The Cancer Genome Atlas; LIPH, Lipase member H; HR, hazard ratio; CI, confidence interval; ER, estrogen receptor; PR, Progesterone receptor; HER2, human epidermal growth factor receptor 2.

Table 4 Univariable Analyses Regarding Proportion Alive Using METABRIC Databases

Characteristics	METABRIC
	Univariable Analysis		Multivariable Analysis
	HR (95% CI)	P	HR (95% CI)	P
LIPH	1.74 (1.27–2.39)	0.001	1.59 (1.08–2.34)	0.019
Grade	1.27 (1.16–1.4)	0	1.15 (1.01–1.3)	0.029
Age	1.04 (1.03–1.04)	0	1.64 (1.46–1.84)	0
Tumor Stage	1.81 (1.62–2.03)	0	1.04 (1.03–1.04)	0
ER Positive	0.85 (0.74–0.98)	0.022	0.81 (0.66–1)	0.054
PR Positive	0.79 (0.7–0.89)	0	0.93 (0.78–1.1)	0.412
HER2 Positive	1.45 (1.22–1.73)	0	1.53 (1.23–1.91)	0

Abbreviations: METABRIC, Molecular Taxonomy of Breast Cancer International Consortium; LIPH, Lipase member H; HR=hazard ratio; CI, confidence interval; ER, estrogen receptor; PR, Progesterone receptor; HER2, human epidermal growth factor receptor 2.

Figure 4 Immunohistochemistry staining of LIPH in the normal breast tissue (A) and breast cancer (B).

Figure 5 Correlation landscape of LIPH expression and immune cell infiltration in pan-cancer.

Abbreviations: ACC, Adrenocortical carcinoma; BLCA, Bladder urothelial carcinoma; BRCA, Breast invasive carcinoma; CESC, Cervical and endocervical cancers; CHOL, Cholangiocarcinoma; COAD, Colon adenocarcinoma; DLBC, Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA, Esophageal carcinoma; GBM, Glioblastoma multiforme; HNSC, Head and Neck squamous cellcarcinoma; KICH, Kidney Chromophobe; KIRC, Kidney renal clear cell carcinoma; KIRP, Kidney renal papillary cellcarcinoma; LAML, Acute Myeloid Leukemia; LGG, Brain Lower Grade Glioma; LIHC, Liver hepatocellular carcinoma; LUAD, Lung adenocarcinoma; LUSC, Lung squamous cell carcinoma; MESO, Mesothelioma; OV, Ovarian serous cystadenocarcinoma; PAAD, Pancreatic adenocarcinoma; PCPG, Pheochromocytoma andParaganglioma; PRAD, Prostate adenocarcinoma; READ, Rectum adenocarcinoma; SARC, Sarcoma; SKCM, Skin Cutaneous Melanoma; STAD, Stomach adenocarcinoma; TGCT, Testicular Germ Cell Tumors; THCA, Thyroid carcinoma; THYM, Thymoma; UCEC, Uterine Corpus Endometrial Carcinoma; UCS, Uterine Carcinosarcoma; UVM, Uveal Melanoma.