. 2019 Sep 24;11:1758835919875851. doi: 10.1177/1758835919875851

Table 1.

Baseline characteristics of the included studies investigating the prognosis.

Gene	First author	Country	Age	Method	Histology	Study design	Specimen type	Cases	Therapy	Method patterns	Cut off	Survival status	Adjusted variables	Prognosis reported	Scores
HIF-1α	Schindl⁵⁹	Austria	52.3	IHC	Advanced breast cancer	Prospective, multicenter	Paraffin-embedded tumor specimens	206	Surgery and combined chemotherapy with tamoxifen	Clone monoclonal antibody H1 67, NB 100–105; Novus Biologicals, Littleton, CO; Dilution: 1:60	Nuclear 10%	5 years	HER-2 staining intensity, patient’s age at time of diagnosis, menopausal status, histological grading, estrogen receptor density, and tumor stage	OS, DFS	29
HIF-1α	Bachtiar⁵⁷	Austria	NA	IHC, blind	Advanced cervical cancer	Retrospective, single-center	Paraffin-embedded tumor specimens	67	Radiotherapy	No. H72320; BD Transduction Laboratories, Franklin Lakes; Dilution: 1:25	Nuclear 10%	3 years	Tumor size, patients’ age, nodal status, FIGO stage, and histological grading	CSS, PFS	29
HIF-1α	Burri⁵⁸	Switzerland	64	IHC, blind	Advanced cervical cancer	Retrospective, NA	Paraffin-embedded tumor specimens	78	Radiotherapy and chemotherapy	H1α67, Novus Biologicals, Littleton, CO; Dilution: 1:5000	Nuclear 0%	5 years	Tumor stage, nodal status, histology, anemia, and median total dose	OS	28
HIF-1α	Theodoropoulos⁵⁶	Greece	68	IHC, blind	Advanced rectal cancer	Retrospective, multicenter	Tissue	92	Surgery, chemotherapy and radiotherapy	Mab H1α67, IgG2b isotype; StressGene, Victoria, British Columbia, Canada; Dilution: 1:1200	Nuclear 10%	3 years	Tumor grade, pattern of tumor growth, vascular invasion, and lymph node status	OS, DFS	24
HIF1α	Winter⁵⁵	UK	NA	IHC	Advanced head and neck squamous cell carcinoma	Retrospective, single-center	Paraffin-embedded tumor specimens	140	Surgery and radiotherapy	ESEE122; Dilution: 1:30	Nuclear 10%	5 years	Advanced disease, anemia, gender, age, smoking history, lymph node status, tumor subsite, and tumor grade	CSS, OS, DFS	22
HIF-1α	Generali⁵⁴	UK	NA	IHC, blind	Advanced breast cancer	Prospective randomized clinical trial, single-center	Paraffin-embedded tumor specimens	187	Surgery and chemoendocrine therapy	ESEE 122, IgG1 monoclonal antibody; Dilution: 1:40	Weak-strong	5 years	T stage, N status, steroid hormone receptor status, c-erb2, bcl2, p53, and Ki67	DFS	29
HIF-1α	Klatte⁵³	USA	NA	IHC, blind	Metastatic clear cell RCC	Retrospective, single-center	Paraffin-embedded tumor specimens	141	Immunotherapy	IgG2b, cloneH1α67-sup, final concentration, 6 Ag/mL; Novus Biologicals; NA	Nuclear 35%	5 years	ECOG PS, T stage, concomitant lymph node metastases, Fuhrman grade, and number of metastatic sites	CSS	23
HIF-1α	Dellas⁵²	Germany	58.4	IHC	Advanced cervical cancer	Retrospective, NA	Paraffin-embedded tumor specimens	44	Radiotherapy	Ab463; Abcam, UK; NA	Nuclear, weak-intensive	5 years	Tumor stage	CSS	15
HIF-1α	Koo and Kim⁵¹	Korea	53.2	IHC	Metastatic squamous cell carcinoma	Retrospective, single-center	Paraffin-embedded tumor specimens	17	Chemo/radiation therapy	EP1215Y, Biocare, CA, USA; Dilution: 1:100	Nuclear or cytoplasmic (or both) 10%	3 years	NDR	OS	11
HIF-1α	Shioya⁴⁸	Japan	59	IHC, blind	Advanced rectal cancer	Retrospective, NA	Paraffin-embedded tumor specimens	50	Surgery and hyperthermo-chemoradiotherapy	Neomarkers, Fremont, CA; Dilution: 1:20000	Nuclear 40%	3 years	Radiation dose, chemotherapy course, treatment time of hyperthermia, age, gender, and stage	RFS, MFS	21
HIF-1α	Xiang⁵⁰	China	50	IHC, blind	Hepatocellular carcinoma with abdominal LN metastases	Retrospective, single-center	Paraffin-embedded tumor specimens	69	Radiotherapy	Santa Cruz Biotechnology, Santa Cruz, CA; NA	Nuclear or cytoplasmic (or both) 10%	3 years	Hb, intrahepatic tumor number, vascular invasion, child-Pugh score, cumber of metastatic LN, and intrahepatic tumor control etc.	OS, RFS	25
HIF-1α	Wan⁴⁷	China	43.1	IHC, blind	Advanced nasopharyngeal carcinoma	Randomized controlled trial	Tissue	144	Chemotherapy and radiotherapy	Millipore, Billerica, MA, USA; Dilution: 1:200	Nuclear or cytoplasmic (or both) 5 scores	5 years	Age, gender, histological style, TNM stage, and Aurora-A	OS, MFS, PFS	25
HIF-1α	Fraga⁴⁹	Brazil	NA	IHC	Upper aerodigestive tract cancer with cervical lymph nodes	Retrospective, single-center	Paraffin-embedded tumor specimens	26	Surgery and radiotherapy	Clone HIF-1α 67, Sigma-Aldrich, St. Louis, USA; NA	NA	3 years	NDR	OS	17
HIF-1α	Shim⁴⁶	Korea	62	IHC, blind	Advanced rectal cancer	Retrospective, single-center	Paraffin-embedded tumor specimens	104	Surgery and chemoradiotherapy	Novus Biologicals, Littleton, CO; Dilution: 1:50	2 scores	3 years	Age and stage	RFS	22
HIF-1α	Shimomura⁴⁵	Japan	62	IHC	Colorectal liver metastasis	Retrospective, single-center	Paraffin-embedded tumor specimens	64	Surgery and chemotherapy	Novus Biologicals, Littleton, CO; Dilution: 1:50	Cytoplasm 5 scores	5 years	N stage, no. of liver tumors, and CEA level etc.	DFS	22
HIF-1α	Wu⁴⁴	China	NA	IHC	Advanced non-small cell lung cancer	Retrospective, single-center	Frozen tissues	162	Chemotherapy	Millipore Corporation^®, USA; Dilution: 1:150	6 scores	NA	Age, sex, smoking status, histology, stage, chemotherapy regimens, and response status	OS	21
HIF-1α	Wilson²³	USA	62	qRT-PCR	Metastatic colorectal cancer	Retrospective, multicenter	Paraffin-embedded tumor specimens	42	FOLFOX4 chemotherapy plus the VEGFR inhibitor PTK787/ZK 222584 (vatalanib)	Applied Biosystems, Foster City, CA, USA; NA	mRNA 1.84 ratio	<3 years	Performance status and serum LDH level	OS	25
HIF-1α	Zhang⁴³	China	NA	IHC, blind	Metastastic esophageal squamous cell carcinoma	Retrospective, single-center	Paraffin-embedded tumor specimens	69	Surgery and radiotherapy/chemotherapy	Clone H1α67; Novus Biologicals, Inc., Littleton, CO; NA	Nucleus and cytoplasm 44%	5 years	NDR	OS, DFS	16
HIF-1α	Braicu⁴²	Germany, Belgium, Austria	58	ELISA	Advanced epithelial ovarian cancer	Prospective, multicenter	Tissue	275	Surgery and platinum-based chemotherapy	ELISA kit (R&D Systems, Inc., Minneapolis, MN, USA; NA	80 pg/mg protein	5 years	Age at first diagnosis, FIGO stage, histological subtype, histological grade, presence and volume of ascites, residual tumor mass after surgery, peritoneal dissemination, and responses to platinum-based chemotherapy	OS	26
HIF-1α	Xie 2015⁴¹	China	63	ELISA, blind	Metastatic renal cell carcinoma	Prospective, open-label, single-arm, multicenter, phase II trial	Serum	86	Second-line treatment with pazopanib after failure of first-line sunitinib treatment	(ELISA) kit (R&D Systems, Minneapolis, MN; NA	80.2 pg/mg protein	<3 years	Previous nephrectomy, six IMDC (International Metastatic RCC Database Consortium) risk factors (anaemia, neutrophilia, Karnofski performance status (KPS) <80%, thrombocytosis, hypercalcaemia, and time from diagnosis to treatment interval <1 year), number of organs involved, and best response to prior sunitinib therapy	OS, PFS	25
HIF-1α	Berk²¹	Turkey	55	IHC	Metastatic colorectal cancer	Retrospective, single-center	Paraffin-embedded tumor specimens	53	Chemotherapy combinations with Bevacizumab	Thermo scientificAb-4, (Clone H1α67, U.K; Dilution: 1:50	Cytoplasm 5 scores	<3 years	Age, gender, K-ras status, dose reduction, dose delay, ECOG PS, metastases, and chemotherapy regimen	OS, PFS	21
HIF-1α	Goos²²	The Netherlands	NA	IHC	Colorectal cancer liver metastasis	Retrospective, multicenter	Paraffin-embedded tumor specimens	328	Surgery and systemic therapy	BD Transduction Laboratories, Breda, The Netherlands; Dilution: 1:500	Nuclear 25%	5 years	Primary tumor-to-CRCLM interval of less than 12 months, lymph node positivity at the time of diagnosis of the primary tumor, maximal CRCLM diameter of greater than 5.0 cm, number of CRCLM greater than 1, and serum CEA level greater than 200 ng/mL	OS	28
HIF-1α	Shultz⁴⁰	USA	NA	Proximity ligation assay/quantitative PCR	Advanced or metastatic pancreatic cancer	Randomized control trial, multicenter	Plasma	229	Gemcitabine and erlotinib	Model 7500, Applied Biosystems; NA	Protein	<3 years	Age, sex, race, ECOG performance status, pain intensity, and disease stage	OS	26
HIF-1α	Chen³⁹	China	53	IHC, blind	Advanced pharyngeal cancer	Retrospective, single-center	Paraffin-embedded tumor specimens	57	Chemoradiotherapy/radiotherapy	Not clear; NA	Nuclear 80%	<3 years	TNM classification, volumetric parameters, texture indices, and primary tumor origin	CSS, RFS	22
HIF-1α	Nyström³⁸	Sweden	71	IHC	Advanced soft tissue sarcoma of extremities and trunk wall	Retrospective, single-center	Tissue	73	Surgery and radiotherapy/chemotherapy	Clone 54, BD Biosciences, Sweden; Dilution: 1:50	Nuclear 10%	5 years	Size, vascular invasion, necrosis, and tumor depth	OS, MFS	22
HIF-1α	Moreno-Acosta³⁷	Colombia	46.3	IHC	Advanced squamous cell cervical carcinoma	Prospective, National Cancer Institute	Fresh tissue	149	Chemo-radiotherapy and brachytherapy	ESEE122, ab8366, abcam; Dilution: 1:400	10%	5 years	FIGO, differentiation degree, treatment type, and anemia	OS, PFS	21
HIF-1α	Beuselinck³⁶	France, Belgium	59	qRT-PCR	Metastatic clear cell renal cell carcinoma	Prospective, multicenter	Tissue	104	Sunitinib	Fluidigm, South San Francisco, CA; NA	mRNA	5 years	Arcomatoid dedifferentiation >25% of tumor volume, neutrophil count, bone metastasis, liver metastasis, and Karnofsky performance status	OS	23
HIF-2α	Winter⁵⁵	United Kingdom	NA	IHC	Advanced head and neck squamous cell carcinoma	Retrospective, single-center	Paraffin-embedded tumor specimens	140	Surgery and radiotherapy	ESEE122; Dilution: 1:30	Nuclear 10%	5 years	Advanced disease, anemia, gender, age, smoking history, lymph node status, tumor subsite, and tumor grade	CSS, OS, DFS	22
HIF-2α	Garcia-Donas⁶⁰	Spain	66	IHC	Advanced clear cell renal cell carcinoma	Prospective, multicenter	Paraffin-embedded tumor specimens	67	Sunitinib	Polyclonal Novus Biologicals NB100–122; Dilution: 1:200	5%	<3 years	MSKCC prognostic classification and gender	OS, PFS	26
HIF-2α	Xie 2015⁴¹	China	63	ELISA, blind	Metastatic renal cell carcinoma	Prospective, open-label, single-arm, multicenter, phase II trial	Serum	86	Second-line treatment with pazopanib after failure of first-line sunitinib treatment	(ELISA) kit (R&D Systems, Minneapolis, MN): NA	80.2 pg/mg protein	<3 years	Previous nephrectomy, six IMDC (International Metastatic RCC Database Consortium) risk factors (anaemia, neutrophilia, Karnofski performance status (KPS) <80%, thrombocytosis, hypercalcaemia, and time from diagnosis to treatment interval <1 year), number of organs involved, and best response to prior sunitinib therapy	OS, PFS	25
HIF-2α	Beuselinck³⁶	France	59	qRT-PCR	Metastatic clear cell renal cell carcinoma	Prospective, multicenter	Tissue	104	Sunitinib	Fluidigm, South San Francisco, CA; NA	mRNA	5 years	Arcomatoid dedifferentiation > 25% of tumor volume, neutrophil count, bone metastasis, liver metastasis, and Karnofsky performance status	OS, PFS	23

CEA, carcino embryonic antigen; CRCLM, colorectal cancer liver metastasis; CSS, cancer-specific survival; DFS, disease-free survival; ECOG PS, Eastern Cooperative Oncology Group performance status; FIGO, International Federation of Gynecology and Obstetrics; Hb, hemoglobin; HIF-1α, hypoxia inducible factor-1α, HIF-2α, hypoxia inducible factor-2α; IHC, immunohistochemistry; LDH, lactate dehydrogenase; LN, lymph nodes; MFS, metastasis-free survival; MSKCC, Memorial Sloan-Kettering Cancer Center; NA, not applicable; NDR, not detailed report; OS, overall survival; PFS, progression-free survival; qRT-PCR, quantitative reverse transcription polymerase chain reaction; enzyme-linked immunosorbent assay; RCC, renal cell carcinoma; RFS, relapse/recurrence-free survival; TNM, tumor node metastasis.