Genetic variability of HIF1A and response to treatment with cisplatin in combination with pemetrexed or gemcitabine in patients with malignant mesothelioma

Characteristic	Category/Unit	N (%) [N]
Sex	Man, N (%)	176 (75.2)
Sex	Woman, N (%)	58 (24.8)
Age	Age, median (25%– 75%)	66 (58–72)
Stage	I	15 (6.4) [1]
	II	53 (22.7)
	III	75 (32.2)
	IV	62 (26.6)
	Peritoneal MM	28 (12.0)
Histological type	Epithelioid	183 (78.2)
	Biphasic	20 (8.5)
	Sarcomatoid	22 (9.4)
	Not specified	9 (3.8)
ECOG performance status	0	15 (6.4)
	1	126 (53.8)
	2	90 (38.5)
	3	3 (1.3)
C-reactive protein (CRP)	Median (25%–75%)	21 (8–59) [19]
Asbestos exposure	No, N (%)	60 (25.8) [1]
Asbestos exposure	Yes, N (%)	173 (74.2)
Smoking	No, N (%)	129 (55.6) [2]
Smoking	Yes, N (%)	103 (44.4)
Pain	No, N (%)	99 (43.4) [6]
Pain	Yes, N (%)	129 (56.6)
Weight loss	No, N (%)	76 (34.4) [13]
Weight loss	Yes, N (%)	145 (65.6)
Type of chemotherapy	Gemcitabine/cisplatin	152 (65.0)
Type of chemotherapy	Pemetreksed/cisplatin	82 (35.0)
Response to chemotherapy	SD+PD	147 (65.0) [8]
Response to chemotherapy	CR+PR	79 (35.0)
Disease progression	No, N (%)	21 (9.1) [3]
Disease progression	Yes, N (%)	210 (90.9)
Death	No, N (%)	65 (27.8)
Death	Yes, N (%)	169 (72.2)
Progression-free survival	Months, median value (25%–75%)	7.9 (5.3–13.8)
Overall survival	Months, median value (25%–75%)	18.2 (9.7–28.0)
Follow-up duration	Months, median valu (25%–75%)	44.4 (20.4–75.5)

1 CR = complete response; ECOG = Eastern Cooperative Oncology Group; N = number of patients; [N] = number of patients with missing data for the given parameter; PD = progressive disease; PR = partial response; SD = stable disease

TABLE 2.

Association between investigated single nucleotide polymorphisms with response and chemotherapy (N = 226)

SNP	Genotype	SD/PD N (%)	CR/PR N (%)	OR (95% CI)	P	OR_adj (95% CI)_adj	P_adj
rs11549465	CC	92 (62.2)	56 (37.8)	Ref.		Ref.
	CT	31 (77.5)	9 (22.5)	0.48 (0.21–1.08)	0.074	0.37 (0.14–0.97)	0.044
	TT	10 (62.5)	6 (37.5)	0.99 (0.34–2.86)	0.979	1.55 (0.48–4.98)	0.464
	CT+TT	41 (73.2)	15 (26.8)	0.60 (0.31–1.18)	0.141	0.60 (0.28–1.30)	0.194
rs11549467	GG	126 (65.6)	66 (34.4)	Ref.		Ref.
	GA+AA	14 (66.7)	7 (33.3)	0.96 (0.37–2.48)	0.924	1.06 (0.38–2.98)	0.906
rs2057482	CC	95 (63.3)	55 (36.7)	Ref.		Ref.
	CT	41 (66.1)	21 (33.9)	0.89 (0.48–1.65)	0.699	0.92 (0.45–1.85)	0.806
	TT	7 (70.0)	3 (30.0)	0.74 (0.18–2.98)	0.672	0.61 (0.11–3.39)	0.574
	CT+TT	48 (66.7)	24 (33.3)	0.86 (0.48–1.56)	0.627	0.87 (0.45–1.71)	0.689

1 adj = adjusted for weight loss and CRP; CR = complete response; CI = confidence interval; N = number of patients; OR = odds ratio; PD = progressive disease; PR = partial response; Ref. = reference genotype; SD = stable disease; SNP = single nucleotide polymorphism

TABLE 3.

Association between investigated polymorphisms and progression-free survival (N = 231)

SNP	Genotype	PFS median (25–75%)	HR (95% CI)	P	HR_adj (95% Cl)_adj	P_adj
rs11549465	CC	7.8 (5.6–13.0)	Ref.		Ref.
	CT	8.9 (5.3–16.2)	0.92 (0.64–1.33)	0.665	0.79 (0.52–1.20)	0.271
	TT	5.6 (3.5–17.4)	1.1 (0.69–1.90)	0.608	0.98 (0.55–1.72)	0.932
	CT+TT	8.5 (4.8–16.2)	0.98 (0.71–1.35)	0.912	0.84 (0.59–1.21)	0.354
rs11549467	GG	7.7 (5.2–13.1)	Ref.		Ref.
	GA+AA	11.2 (7.7–16.0)	0.74 (0.46–1.19)	0.220	0.67 (0.40–1.11)	0.119
rs2057482	CC	8.9 (5.5–16.0)	Ref.		Ref.
	CT	7.9 (5.3–12.4)	1.21 (0.89–1.65)	0.223	1.35 (0.95–1.92)	0.099
	TT	7.6 (5.5–8.3)	1.63 (0.83–3.21)	0.158	1.41 (0.65–3.07)	0.390
	CT+TT	7.6 (5.3–11.9)	1.25 (0.93–1.68)	0.131	1.35 (0.97–1.89)	0.076

1 adj = adjusted for CRP, histological type, weight loss, asbestos exposure, and smoking; CI = confidence interval; HR = hazard ratio; PFS = progression-free survival; Ref. = reference genotype; SNP = single nucleotide polymorphism

TABLE 4.

Association between investigated polymorphisms and overall survival (N = 234)

SNP	Genotype	OS median (25%–75%)	HR (95% CI)	P	HR_adj (95% CI)_adj	P_adj
rs11549465	CC	18.1 (9.9–28.0)	Ref.		Ref.
	CT	21.0 (6.8–29.8)	0.85 (0.56–1.30)	0.451	0.75 (0.47–1.19)	0.217
	TT	20.3 (9.1–32.5)	1.00 (0.56–1.77)	0.994	0.85 (0.46–1.59)	0.610
	CT+TT	21.0 (8.7–29.8)	0.89 (0.62–1.28)	0.542	0.78 (0.52–1.16)	0.215
rsll549467	GG	18.1 (9.2–28.7)	Ref.		Ref.
	GA+AA	22.2 (12.6–29.6)	0.90 (0.55–1.48)	0.687	0.95 (0.56–1.60)	0.847
rs2057482	CC	19.6 (9.8–27.9)	Ref.		Ref.
	CT	18.0 (9.8–29.7)	1.07 (0.76–1.50)	0.694	1.07 (0.74–1.52)	0.729
	TT	11.6 (9.4–22.1)	1.44 (0.70–2.95)	0.325	1.43 (0.66–3.10)	0.366
	CT+TT	15.6 (9.8–29.7)	1.11 (0.81–1.53)	0.529	1.10 (0.78–1.55)	0.573

1 adj = adjusted for CRP, histological type, and smoking; CI = confidence interval; HR = hazard ratio; OS = overall survival; Ref. = reference genotype; SNP = single nucleotide polymorphism

Articles in this issue

DOI: https://doi.org/10.2478/raon-2025-0049 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 403 - 411

Submitted on: Jun 15, 2025

Accepted on: Jul 19, 2025

Published on: Sep 5, 2025

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

malignant mesothelioma,

chemotherapy,

hypoxia-inducible factor,

Related subjects:

© 2025 Matic Setina, Eva Setina, Ziga Doljak, Katja Goricar, Vita Dolzan, Viljem Kovac, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 59 (2025): Issue 3 (September 2025)