Prevalence and prognosis of malignancy in THSD7A-associated membranous nephropathy: a systematic literature review and clinical case study

Figures & data

Figure 1. Study selection flowchart.

Figure 2. Forest plot of malignancy prevalence in THSD7A-associated MN.

Figure 3. Funnel plot of including studies.

Figure 4. Representative images of glomerular and tumor staining for THSD7A. (A) Patient no. 13 with positive glomerular THSD7A staining. (B) Patient no. 14 with positive glomerular THSD7A staining. (C) Patient no. 15 with positive glomerular THSD7A staining. (D) Patient no. 14 with positive THSD7A staining of small cell lung cancer tissue (immunohistochemistry staining, magnification ×400).

Table A1. Quality evaluation of each study using the Newcastle-Ottawa Quality Assessment Scale.

No.	Study	Selection	Comparability	Exposure	Quality scores
1	Caza et al. [12]	***	*	***	7
2	von Haxthausen et al. [13]	**	*	**	5
3	Hoxha et al. [9]	***	*	**	6
4	Hara et al. [14]	**	*	**	5
5	Sharma and Larsen [15]	**	*	**	5
6	Zaghrini et al. [16]	***	**	***	8
7	Hanset et al. [17]	**	**	***	7
8	Wang et al. [10]	**	*	**	5
9	Jianing [18]	**	*	**	5

Table 1. Literature review of malignancy in THSD7A-associated MN.

No.	Study	Number of patients with THSD7A-associated MN	Age (years)	Men (%)	Primary MN	Malignancy in MN (%)	Type of neoplasm	Quality scores
1	Caza et al. [12]	37	NA	NA	33 (89.2)	4 (10.8)	3 prostate carcinoma, 1 breast carcinoma, 1 renal cell carcinoma, 1 squamous cell carcinoma (head/neck)	7
2	von Haxthausen et al. [13]	41	65 (55–75)	24 (58.5)	34 (82.9)	7 (17.1)	1 prostate carcinoma, 2 colon cancer, 2 gastric carcinoma, 1 lung carcinoma, 1 uterine carcinoma	5
3	Hoxha et al. [9]	40	60.5 (46–73.25)	17 (42.5)	32 (80.0)	8 (20.0)	2 prostate carcinoma, 1 colon cancer, 1 gall bladder cancer, 1 gastrointestinal stroma tumor, 1 gynecologic tumor, 1 malt lymphoma, 1 endometrium carcinoma	6
4	Hara et al. [14]	14	64 (42–79)	9 (64.3)	12 (85.7)	2 (14.3)	1 prostate carcinoma, 1 lung carcinoma	5
5	Sharma and Larsen [15]	31	62 (17–91)	19 (61.3)	29 (93.5)	2 (6.5)	1 breast carcinoma, 1 thyroid carcinoma	5
6	Zaghrini et al. [16]	49	59.9 (48.5–75.0)	28 (57.1)	41 (83.7)	8 (16.3)	2 prostate carcinoma, 1 breast carcinoma, 1 colon cancer, 1 gastric carcinoma, 1 hepatocellular carcinoma, 1 cheek intra-epidermal cancer, 1 pancreatic cancer, 1 rectal cancer, and thymoma	8
7	Hanset et al. [17]	6	58.8 (44.3–66.5)	1 (16.7)	3 (50.0)	3 (50.0)	1 squamous cell carcinoma (head/neck), 1 gastric carcinoma, 1 hepatocellular carcinoma	7
8	Wang et al. [10]	13	52 (18)	8 (66)	12 (92.3)	1 (7.7)	1 unknown type	5
9	Jianing [18]	4	NA	NA	3 (75.0)	1 (25.0)	1 kidney cancer

Table 2. Clinical manifestations and prognosis of 15 patients with THSD7A-associated MN in our center.

Patient ID	Gender	Age (years)	UProt. (g/day)	Alb. (g/L)	Scr (μmol/L)	eGFR (mL/min/1.73 m^2)	Secondary etiology	Time of diagnosis of tumor to MN diagnosis (months)*	Treatment	MN outcome
1	M	42	4.96	17	57.5	119.8	None	–	ARB	PR
2	F	65	8.62	26	83.2	76.1	None	–	Glucocorticoid + CsA	CR
3	F	61	6.04	27	52.1	99.1	None	–	ARB	PR
4	F	51	1.18	38	73.8	93.8	None	–	ARB	CR
5	F	53	0.61	35	53.4	103.9	None	–	Glucocorticoid	CR
6	F	29	3.38	23	62.5	116.2	None	–	Glucocorticoid	CR
7	M	28	0.31	49	77.9	116.9	None	–	ARB	CR
8	M	63	5.56	24	92.5	75.8	None	–	Glucocorticoid	CR
9	F	51	1.64	36.9	73.8	93.8	None	–	ARB	PR
10	F	62	0.39	37.2	44.2	104.5	None	–	ARB	CR
11	F	53	3.41	35	48.6	97.7	None	–	ARB	NS
12	M	56	0.51	30.7	77.1	97.1	None		ARB	CR
13	F	47	2.74	36	44.6	115.8	Adenocarcinoma of lung	9	Resection of the lower lobe of the right lung	CR
14	M	63	14.67	24	65.4	98.3	Small cell lung cancer with multiple metastases	13	Chemotherapy	CR
15	M	61	4.92	25.7	72.6	97.55	Adenocarcinoma of lung	0	Resection of the upper lobe of the right lung	CR

Table 3. Immunofluorescence deposition of renal tissue in 15 patients with THSD7A-associated MN.

Patient ID	IgG deposition	IgM deposition	IgA deposition	C3 deposition	C1q deposition	FRA deposition	IgG1 deposition	IgG2 deposition	IgG3 deposition	IgG4 deposition
1	4	0	3	3	2	2	3	2	0	3
2	3	2	2	2	1	2	3	2	0	3
3	3	2	1	0	0	1	2	2	0	2
4	3	2	2	2	1	2	3	0	0	2
5	3	2	2	2	2	2	2	2	0	2
6	3	0	1	2	0	0	2	0	0	0
7	3	2	2	1	2	1	3	1	0	2
8	3	2	2	2	1	2	3	2	0	2
9	3	2	2	2	1	0	3	0	0	2
10	2	0	0	1	2	2	2	0	0	2
11	3	2	2	2	0	2	2	2	0	1
12	3	0	2	1	1	2	2	0	0	0
13	2	1	0	3	0	1	2	1	1	0
14	3	2	2	2	2	1	3	2	0	0
15	3	2	2	2	1	1	2	2	0	1

Table 4. Serum antibodies and antigen staining of renal tissues in 15 cases of THSD7A-associated MN.

Patient ID	Anti-PLA2R antibody	Anti-THSD7A antibody	PLA2R staining	THSD7A staining	NELL1 staining	SEMA3B staining	PCDH7 staining	NCAM1 staining	EXT1 staining
1	–	–	–	+	–	–	–	–	–
2	–	–	–	+	–	–	–	–	–
3	–	–	–	+	–	–	–	–	–
4	–	+	+	+	–	–	–	–	–
5	–	–	–	+	–	–	–	–	–
6	–	–	+	+	–	–	–	–	–
7	+	–	+	+	–	–	–	–	–
8	–	+	–	+	–	–	–	–	–
9	–	–	+	+	–	–	–	–	–
10	–	–	–	+	–	–	–	–	–
11	–	–	–	+	–	–	–	–	–
12	–	–	–	+	–	–	–	–	–
13	–	+	–	+	–	–	–	–	–
14	–	–	–	+	–	–	–	–	–
15	–	–	–	+	–	–	–	–	–

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Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.