Abstract
Long non-coding RNA (lncRNA) CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP) rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29–0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30–0.89, p = 0.02, respectively). It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05–2.39, p = 0.03). Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC) subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35–0.98, p = 0.04) and in additive model (adjusted OR = 0.62, 95%CI = 0.43–0.90, p = 0.01). Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36–45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07–3.53, p = 0.03, respectively). Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients.
Highlights
Lung cancer, containing two primary subtypes: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), is a major cause of cancer-related death globally, with an extremely poor overall survival rate [1]
Four-hundred ninety-eight lung cancer patients (189 with squamous cell carcinoma, 217 with adenocarcinoma, 69 with small cell carcinoma, and 23 with others) and 213 healthy control subjects were recruited in our study
We found that Cancer susceptibility candidate 8 (CASC8) rs10505477 polymorphism was statistically correlated with severe hematologic toxicity in NSCLC subgroup in dominant and additive models
Summary
Lung cancer, containing two primary subtypes: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), is a major cause of cancer-related death globally, with an extremely poor overall survival rate [1]. NSCLC, accounting for the most of lung cancers, approximately 85%, could be further classified as squamous-cell carcinoma (SCC), adenocarcinoma (ADC), and large-cell carcinoma [2]. Cigarette smoking is a well-known major risk factor, genetic factors are reported to be associated with lung cancer susceptibility [3,4,5]. Platinum-based cytotoxic chemotherapy, one of the various treatment options in clinic, is the standard first-line treatment for lung cancer. Low objective response rate (ORR) or serious toxicity reaction in some lung cancer patients is often observed in clinic. Late diagnosis, chemoresistance, and toxicity are considered to be major factors that contributed to the poor outcome of lung cancer patients. It is urgent to seek out new biomarkers that can accurately predetermine the susceptibility, chemotherapy response, and/or toxicity for lung cancer patients
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