Id-1, Id-2, and Id-3 co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy

Abstract

Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T 1 -stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P ¼ 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P ¼ 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P ¼ 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.

Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy

“…Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC). Study shows that Id1 and Id3 co-expression is associated with a poor clinical outcome in patients with locally advanced NSCLC [19,20]. In analysis of 532 NSCLC patients' samples, Id1 was found significantly correlated with EMT-related proteins and it enables the tumor and the microenvironment to colonize the liver.…”

LEF1/Id3/HRAS axis promotes the tumorigenesis and progression of esophageal squamous cell carcinoma

“…The inhibitor of DNA binding (Id) protein includes Id1, Id2, Id3, and Id4 members, function as inhibitors of basic helix-loop-helix (bHLH) transcription factors [10]. As vital regulators of cell cycle, cell growth and differentiation, Id proteins are increasingly observed involving in various tumor-related processes, such as chemotherapeutic drug resistance [11], stem cell features [12], metabolic reprogramming [13], EMT [14], angiogenesis and metastasis [15]. However, studies about the role of Id proteins in ESCC were limited, especially for Id3.…”

A study of the impact of inhibitors of DNA binding‐1 on proliferation and migration in human colon carcinoma cells

“…[1][2][3] Its overexpression is closely correlated to the occurrence, development, and prognoses of many malignant tumors such as lung cancer, gastric cancer, pancreatic cancer, and cervical cancer. 4 A previous study has suggested that the overexpression of Id-1 is closely correlated to occurrence and development of colorectal cancer. 5 However, there are no detailed reports on its corresponding proliferation in vitro and invasion experiments.…”

“…This gene can promote cell proliferation, induce the generation of blood vessel endothelia with tumors, and promote tumor growth and invasion . Its overexpression is closely correlated to the occurrence, development, and prognoses of many malignant tumors such as lung cancer, gastric cancer, pancreatic cancer, and cervical cancer . A previous study has suggested that the overexpression of Id‐1 is closely correlated to occurrence and development of colorectal cancer .…”