Abstract
Pulmonary malignancies with neuroendocrine differentiation represent a rare subclass of lung carcinomas, which vary in the extent of differentiation and grade of biological aggressiveness. In particular, neuroendocrine tumors are classified into well differentiated typical and atypical carcinoids as well as poorly differentiated large cell neuroendocrine and small cell lung carcinomas. Tiny MicroRNAs have been identified as reliable classifiers in distinct cancer types and seem to play important roles in cellular processes like regulation of cell growth, differentiation and apoptosis. In the present study, two different microRNAs (miR-21 and miR-34a) were explored for their involvements in pathogenesis of subtypes and finally in differential diagnosis of pulmonary neuroendocrine tumors. miR-21 was upregulated in poorly differentiated neuroendocrine tumors (mean rank: 26.8; 28.75) as compared to carcinoids (mean rank: 12.33; 12.07) with a significance of 0.00033. High-expression levels of miR-34a were associated with atypical carcinoids (p = 0.010). A close association is implicated between the elevated miR-21 values in high-grade and miR-34a patterns in low-grade atypical neuroendocrine lung carcinomas, which could potentially be exploited as practical supportive markers for differential lung cancer diagnosis in routine. However, some additional extended research and validation studies are needed to utilize them as routine markers or potential molecular targets for personalized medicine.
Highlights
Lung cancer is still the leading cause of cancer-related death worldwide, often diagnosed at advanced stages and with one of the poorest prognoses of all types of cancer
Lung tumors with neuroendocrine differentiation are further subdivided into four subtypes, low grade (G1) typical carcinoid (TC), intermediate grade (G2) atypical carcinoid (AC), high grade (G3) large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC)
LCNECs are involved in 3% and SCLCs in 15 to 20% of all lung carcinoma distribution is not reflected in the study,study, due todue the strong carcinomacases cases[22]
Summary
Lung cancer is still the leading cause of cancer-related death worldwide, often diagnosed at advanced stages and with one of the poorest prognoses of all types of cancer. A linearly increasing incidence of neuroendocrine tumors is noticeable [1]. Neuroendocrine tumors (NETs) are generally found throughout the human body, but most commonly in the small intestine (30.4%) and the lung (29.8%) [2,3]. Lung tumors with neuroendocrine differentiation are further subdivided into four subtypes, low grade (G1) typical carcinoid (TC), intermediate grade (G2) atypical carcinoid (AC), high grade (G3) large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). When looking at the distribution of NET subtypes, carcinoids comprise for 1% to 2%, LCNECs for 3% and SCLCs for 15% to 20% of all lung cancer malignancies [4]. LCNECs and SCLCs are associated with older age and more smoking compared to TCs and ACs. Generally, carcinoid tumors (especially those located in the periphery) are accompanied
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