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Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance

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Abstract

Purpose

The assessment of single gene such as ERCC1, TYMS, RRM1, TUBB3, EGFR, KRAS, BRAF, PIK3CA, ALK, and ROS1 is now widely applied in therapeutic decisions of non-small cell lung cancer (NSCLC). The aim of our study was to concurrently analyze these genes and evaluate their clinical significance in patients with NSCLC.

Methods

Rearrangement of ALK and ROS1 was analyzed in 120 patients using FISH assays. Somatic mutation of EGFR, KRAS, BRAF, PIK3CA and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR were examined by liquidchip platform in 350 patients . Data on clinical features were obtained from medical records of 119 patients, and the follow-up was conducted in 106 patients who received platinum-based adjuvant chemotherapy.

Results

We identified 5.0 % ALK rearrangements, 1.7 % ROS1 rearrangements, 36.6 % EGFR mutations, 8.9 % KRAS mutations, 0 % BRAF mutations, and 4.0 % PIK3CA mutations. Double or coexisting mutations were identified in 13 patients. Significant correlations were observed among EGFR, KRAS mutation, ERCC1, TYMS, RRM1, TUBB3, EGFR expression, and clinical features, especially histology (P < 0.05). Significant cross-correlations were observed in some pairs of genes (P < 0.05). Patients with low RRM1 expression had a better progression-free survival (PFS) (P < 0.05). Furthermore, EGFR-mutated patients with low RRM1 expression or patients with both ERCC1 and RRM1 low expression had a better PFS (P < 0.05).

Conclusion

Combined analysis of these commonly studied genes may promote the individual treatment in NSCLC. RRM1 may be a prognostic and predictive biomarker for PFS in patients with NSCLC who received platinum-based adjuvant chemotherapy, and combining EGFR mutation and RRM1 expression or combining ERCC1 and RRM1 expression can enhance prognostic and predictive power for PFS.

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Acknowledgments

The authors sincerely thank all the investigators and coordinators who contributed to this study.

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    Authors and Affiliations

    1. Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, The Third Military Medical University, Chongqing, People’s Republic of China

      Quan Zhang, Tianyu Sun, Poming Kang, Kai Qian, Bo Deng, Jinghai Zhou, Ruwen Wang, Bin Jiang, Kun Li & Qunyou Tan

    2. SurExam Bio-Tech, Guangzhou Technology Innovation Base, 80 Lan Yue Road, Science City, Guangzhou, People’s Republic of China

      Fang Liu & Shiyang Wu

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    1. Quan Zhang
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    Quan Zhang and Tianyu Sun are co-first authors, and they contributed equally to this study.

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    Zhang, Q., Sun, T., Kang, P. et al. Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance. Cancer Chemother Pharmacol 77, 583–593 (2016). https://doi.org/10.1007/s00280-016-2969-y

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